GT HoaSinhDongVat

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vn
B GIO DC V O TO
TRNG I HC NNG NGHIP H NI
nguyn vn kim (Ch bin)
nguyn vn knh , nguyn vn mi

Ho sinh ng vt

Animal Biochemistry

H ni H ni H ni H ni - -- -2005 2005 2005 2005
http://www.ebook.edu.vn
Li ni u Li ni u Li ni u Li ni u

Tt c cc qa trnh sinh trng, ph Tt c cc qa trnh sinh trng, ph Tt c cc qa trnh sinh trng, ph Tt c cc qa trnh sinh trng, pht trin hay s tin trin ca bnh t trin hay s tin trin ca bnh t trin hay s tin trin ca bnh t trin hay s tin trin ca bnh
tt u din ra trong t bo. m nhim c nhng chc nng y, c th sng tt u din ra trong t bo. m nhim c nhng chc nng y, c th sng tt u din ra trong t bo. m nhim c nhng chc nng y, c th sng tt u din ra trong t bo. m nhim c nhng chc nng y, c th sng
c cc phn t c bit nh protein, saccharide, lpipide, nc v c acid c cc phn t c bit nh protein, saccharide, lpipide, nc v c acid c cc phn t c bit nh protein, saccharide, lpipide, nc v c acid c cc phn t c bit nh protein, saccharide, lpipide, nc v c acid
nucleic v. v. Cc phn t ny l nhng vin gch to nn t bo, nucleic v. v. Cc phn t ny l nhng vin gch to nn t bo, nucleic v. v. Cc phn t ny l nhng vin gch to nn t bo, nucleic v. v. Cc phn t ny l nhng vin gch to nn t bo, m, v cc m, v cc m, v cc m, v cc
c quan ca c th vi mc chuyn ho tinh vi c bit, m bo cho c th tn c quan ca c th vi mc chuyn ho tinh vi c bit, m bo cho c th tn c quan ca c th vi mc chuyn ho tinh vi c bit, m bo cho c th tn c quan ca c th vi mc chuyn ho tinh vi c bit, m bo cho c th tn
ti v pht trin mt cch bnh thng . ti v pht trin mt cch bnh thng . ti v pht trin mt cch bnh thng . ti v pht trin mt cch bnh thng .
Ho sinh ng vt c xut bn ln ny vi mc ch phc v ch yu Ho sinh ng vt c xut bn ln ny vi mc ch phc v ch yu Ho sinh ng vt c xut bn ln ny vi mc ch phc v ch yu Ho sinh ng vt c xut bn ln ny vi mc ch phc v ch yu
cho cc bn c ca ngnh chn nui th y cc trng cho cc bn c ca ngnh chn nui th y cc trng cho cc bn c ca ngnh chn nui th y cc trng cho cc bn c ca ngnh chn nui th y cc trng nng nghip v cc nng nghip v cc nng nghip v cc nng nghip v cc
ngnh c lin quan. Cc vn u c cp nht ti nm 2004. ngnh c lin quan. Cc vn u c cp nht ti nm 2004. ngnh c lin quan. Cc vn u c cp nht ti nm 2004. ngnh c lin quan. Cc vn u c cp nht ti nm 2004.
Sch gm 10 chng cp ti hu ht cc ni dung ca sinh hc phn Sch gm 10 chng cp ti hu ht cc ni dung ca sinh hc phn Sch gm 10 chng cp ti hu ht cc ni dung ca sinh hc phn Sch gm 10 chng cp ti hu ht cc ni dung ca sinh hc phn
t v vn cu trc v qu trnh chuyn ho vt cht cu to nn c th t v vn cu trc v qu trnh chuyn ho vt cht cu to nn c th t v vn cu trc v qu trnh chuyn ho vt cht cu to nn c th t v vn cu trc v qu trnh chuyn ho vt cht cu to nn c th
sng, nh protein, acid nuclei sng, nh protein, acid nuclei sng, nh protein, acid nuclei sng, nh protein, acid nucleic, cc qu trnh phin m v gii m ADN, qu c, cc qu trnh phin m v gii m ADN, qu c, cc qu trnh phin m v gii m ADN, qu c, cc qu trnh phin m v gii m ADN, qu
trnh chuyn ho, hp thu cc cht trong c th, qu trnh tng hp ATP, vic trnh chuyn ho, hp thu cc cht trong c th, qu trnh tng hp ATP, vic trnh chuyn ho, hp thu cc cht trong c th, qu trnh tng hp ATP, vic trnh chuyn ho, hp thu cc cht trong c th, qu trnh tng hp ATP, vic
to v s dng nng lng cho cc hot ng sng. S iu ho cc qu trnh to v s dng nng lng cho cc hot ng sng. S iu ho cc qu trnh to v s dng nng lng cho cc hot ng sng. S iu ho cc qu trnh to v s dng nng lng cho cc hot ng sng. S iu ho cc qu trnh
trao i cht hay s khng li cc tc nhn gy bnh. trao i cht hay s khng li cc tc nhn gy bnh. trao i cht hay s khng li cc tc nhn gy bnh. trao i cht hay s khng li cc tc nhn gy bnh.
Ni dung ca cun sch cn cha ng nhiu kha cnh khoa hc c Ni dung ca cun sch cn cha ng nhiu kha cnh khoa hc c Ni dung ca cun sch cn cha ng nhiu kha cnh khoa hc c Ni dung ca cun sch cn cha ng nhiu kha cnh khoa hc c
tnh thi s nh s hon thin v nh c ca cc chui polypeptide tnh thi s nh s hon thin v nh c ca cc chui polypeptide tnh thi s nh s hon thin v nh c ca cc chui polypeptide tnh thi s nh s hon thin v nh c ca cc chui polypeptide sau khi c sau khi c sau khi c sau khi c
tng hp. y l c s ca bnh l hc mc phn t, t bo. tng hp. y l c s ca bnh l hc mc phn t, t bo. tng hp. y l c s ca bnh l hc mc phn t, t bo. tng hp. y l c s ca bnh l hc mc phn t, t bo.
Ho sinh ng vt vi ni dung hin hu ca Ho sinh ng vt vi ni dung hin hu ca Ho sinh ng vt vi ni dung hin hu ca Ho sinh ng vt vi ni dung hin hu ca n cng c th l ti liu n cng c th l ti liu n cng c th l ti liu n cng c th l ti liu
tham kho hu ch cho cc sinh vin thuc cc trng khoa hc c bn, cc tham kho hu ch cho cc sinh vin thuc cc trng khoa hc c bn, cc tham kho hu ch cho cc sinh vin thuc cc trng khoa hc c bn, cc tham kho hu ch cho cc sinh vin thuc cc trng khoa hc c bn, cc
trng s phm, cc trng y, dc hc. trng s phm, cc trng y, dc hc. trng s phm, cc trng y, dc hc. trng s phm, cc trng y, dc hc.
Cc tc gi tuy c nhiu c gng v ni dung v cch trnh by. Song Cc tc gi tuy c nhiu c gng v ni dung v cch trnh by. Song Cc tc gi tuy c nhiu c gng v ni dung v cch trnh by. Song Cc tc gi tuy c nhiu c gng v ni dung v cch trnh by. Song
chc thiu st trong cun sch ny l chc thiu st trong cun sch ny l chc thiu st trong cun sch ny l chc thiu st trong cun sch ny l kh trnh khi. V vy chng ti mong kh trnh khi. V vy chng ti mong kh trnh khi. V vy chng ti mong kh trnh khi. V vy chng ti mong
rng sau khi s dng cun sch ny, s c c gi gp nhiu kin b ch rng sau khi s dng cun sch ny, s c c gi gp nhiu kin b ch rng sau khi s dng cun sch ny, s c c gi gp nhiu kin b ch rng sau khi s dng cun sch ny, s c c gi gp nhiu kin b ch
cun sch ngy cng hon thin hn. cun sch ngy cng hon thin hn. cun sch ngy cng hon thin hn. cun sch ngy cng hon thin hn.

H ni, thng 12 nm 2004 H ni, thng 12 nm 2004 H ni, thng 12 nm 2004 H ni, thng 12 nm 2004

Cc tc gi Cc tc gi Cc tc gi Cc tc gi

Mc lc
Trang
m u

Sinh ho hc v vai tr ca sinh ho hc

TS. Nguyn Vn Kim
1

Chng I
Protein

PGS.TS Nguyn Vn Knh, TS. Nguyn Vn Kim
3
1.
Khi nim v chc nng ca protein 3
2.
Cu to ca protein 4
2.1.
Axit amin - n v cu to nn protein 4
2.2.
Cu trc bc I ca protein 10
2.3
Cu trc bc II ca protein 12
2.4
Cu trc bc III ca protein 14
2.5
Cu trc bc IV ca protein 17
3.
Ct v sa i protein to nn kh nng mi 17
4.
Bn mc cu trc ca protein 22
5.
Sequence amino axit chuyn ho cu trc khng gian ca protein 23
6.
S gn c hiu v nhng thay i cu trc l c s ca tc ng protein 26
7.
c tnh l ho ca protein 28
8.
Phn loi protein 29

Chng II
Axit nucleic v c ch di truyn t bo

PGS.TS. Nguyn Vn Mi, TS. Nguyn Vn Kim

34
1.
Khi nim v axit nucleic 34
2.
Cu trc ca axit nucleic 34
2.1.
Mononucleotit 34
2.2.
Dinucleotit 42
2.3.
Cu trc bc I ca axit nucleic 43
2.4.
Cu trc bc II ca axit nucleic 45
2.5.
Cu trc bc III v siu cu trc ca axit nucleic 49
3.
Phn loi axit nucleic 49
4.
Phc hp axit nucleic -protein 54
5.
S phn gii axit nucleic 56
6.
S tng hp axit nucleic 59

Chng III
ENzyme

71
1.
Khi nim v enzyme 71
2.
Bn cht ca enzyme 71
3.
Trung tm hot ng ca enzyme 72
4.
Cht phi hp ca enzyme 74
5.
c im ho tnh ca enzyme 83
6.
Tn gi v phn loi enzyme 84
7.
C ch xc tc ca enzyme 86
8.
ng hc enzyme 91
9.
V d v phn ng xc tc ca enzyme 94
10.
Enzyme iu ho 96

Chng IV
Sinh ho hormone

TS. Nguyn Vn Kim
98
1.
i cng v hormone 98
2.
Phn loi hormone 102
3.
C ch tc dng ca hormone 104
3.1.
Hai nguyn l c bn v tc dng ca hormone 104
3.2.
C ch tc dng ca hormone 105
3.2.1.
C ch tc dng ln mng 106
3.2.2.
C ch tc dng ln gen 113
4.
Mt s hormone v vai tr ca chng 117
4.1.
Adrenalin v Noradrenalin 117
4.2.
Glucagon 118
4.3.
Insulin 119
4.4.
Tc trao i cht c bn v hormone tuyn gip 123

Chng V
Trao i vt cht v nng lng

126
1.
Trao i vt cht l g? 126
2.
Trao i nng lng 129
2.1.
Sinh vt sng bng nng lng g? 129
2.2.
S h hp m bo 130
2.3.
Qu trnh phosphoryl ho 137

Chng VI
Gluxit v qu trnh chuyn ho gluxit

PGS.TS. Nguyn Vn Mi, TS. Nguyn Vn Kim
142
1.
Khi nim v vai tr v gluxit 142
2.
Phn loi gluxit 143
3.
Tiu ho, hp thu v d tr gluxit ng vt 144
3.1.
Tiu ho, hp thu tinh bt 144
3.2.
Sinh tng hp glycogen 146
3.3.
S phn gii glycogen 148
3.4.
S tiu ho v hp thu cht x 151
4.
S chuyn ho trung gian ca glucose 154
4.1.
Khi qut v s chuyn ho glucose 154
4.2.
Cch phn gii ym kh glucose m bo ng vt - Qu trnh ng phn 154
4.3.
Qu trnh ln men ru etylic 169
4.4.
S ln men vi sinh vt to thnh cc sn phm c gi tr thng mi 170
4.5.
Cc monosaccharide khc c th i vo con ng ng phn 170
5.
S oxy ho glucose trong iu kin c oxy 172
5.1.
Oxy ho theo vng Krebs 173
5.2.
Cc con ng th cp ca s oxy ho glucose 192
6.
S iu ho trao i gluxit 198
7.
Mt s bnh do ri loi trao i ng 202

Chng VII
Lipid v s chuyn ho lipid

TS. Nguyn Vn Kim
204
1.
i cng v lipid 204
2.
Mt s c im v tiu ho, hp thu, vn chuyn v d tr lipid ng vt 205
3.
S phn gii triglyceride 209
4.
S hnh thnh v chuyn ho th xeton 216
5.
Tng hp axit bo v triglyceride 220
6.
S lc v vai tr v s chuyn ho cc dng lipoide 225
7.
iu ho qu trnh chuyn ho lipid 227

Chng VIII
Trao i protein

228
1. ngha ca s chuyn ho protein ng vt
228
2.
c im ca trao i protein ng vt 228
3.
Tiu ho v hp thu protein 229
4.
S chuyn ho trung gian ca axitamin 233
4.1.
Phn ng kh amin 233
4.2.
Phn ng chuyn amin 235
4.3.
Phn ng kh carboxyl 236
5.
S thi ra prtein rut gi do vi khun 239
6.
S bi tit cc cht cn b cha nit 240
6.1.
S vn chuyn amiac trong c th 240
6.2.
S tng hp v bi tit ure (vng ornitin) 241
6.3
S bi tit axit uric 242
7.
S chuyn ho ca cc protein phc tp 244
7.1.
S chuyn ho ca hemoglobin 244
7.2.
Ri lon chuyn ho hemoglobin 245
8.
Qu trnh sinh tng hp protein 246
8.1. ngha ca qu trnh
246
8.2.
Sinh tng hp theo khun mu 247
8.3
Tng hp protein ty lp th 261
8.4.
iu ho tng hp protein 261
9.
S hon thin phn t protein sau khi c tng hp 264
10.
S bin i mt s protein xut ngoi 265
11.
S gluxit ho protein 266
12.
Cc protein i vo ty lp th 268
13.
Cc protein nhn t bo 269

Chng IX
Min dch hc

PGS.TS Nguyn Vn Knh
270
1.
H thng min dch ca c th 270
1.1.
H thng min dch t bo 270
1.2.
H thng min dch th dch 273
1.3.
H thng min dch l h thng t dung np 274
2.
Cu trc v vai tr ca khng th (immunoglobulin) 275
3.
Khng th n dng 282
4.
V tr gn khng nguyn ca khng th 282
5.
S pht sinh tnh a dng ca khng th 284
6. Cc chui nh
287
7.
S lp rp cc gen chui nng 287
8.
Protein RAG1 v RAG2 289
9.
t bin dinh dng 289
10.
S loi tr alen m bo cho khng th c tnh c hiu cao 290
11.
S chuyn i t dng lin kt mng n dng tit ca mt khng th 290
12.
S chuyn lp immunoglobulin ca cc t bo B 291
13.
Receptor t bo T 292
14.
Phc hp ho hp t chc chnh 294
15.
H thng b th 297
16.
Vaccine ca hin ti v tng lai 303

Chng X
S vn chuyn cht qua mng

PGS.TS Nguyn Vn Knh
305
1.
Nhng nt i cng v mng t bo 305
2.
Thnh phn ho hc ca mng t bo 305
3.
S vn chuyn cc cht qua mng 307
4.
S vn chuyn tch cc qua lp t bo
Trng i hc Nng nghip H Ni Gio trnh Ho Sinh ng vt 1
M U
HO SINH HC V VAI TR CA HO SINH HC
Ho sinh hc l mn hc c s, c nhim v nghin cu s sng v mt ho hc trn hai
phng din:
Nghin cu v cu to, thnh phn ho hc, tnh cht l ho, chc nng sinh hc ca cc
cht trong c th sng: mu, c, no, sinh dch...
Nghin cu v s chuyn ho ca cc thnh phn cu to nn c th sng, l s trao
i vt cht (TVC) trong c th, l cc qu trnh chuyn ho, s bin i ca cc cht, s
tng hp, phn gii t nhng sn phm chuyn ho to nn nhng cht cu to nn c th.
TVC gia c th sng v mi trng gm nhiu mt, nhiu qu trnh c lin quan cht ch
vi nhau, d hiu ngi ta tch chng ra thnh tng qu trnh nh trao i protein, trao i
lipid, trao i ng...
T ho sinh ln u tin c nh ho hc c Carl Neuberg (1903) xut t hai ch
ho v sinh ( Biochemistry, Bio: l s sng).
Ho sinh c hnh thnh t s pht trin ca cc mn ho hc v sinh hc vo cui th
k XIX v u th k XX, da vo s tin b ca cc ngnh khoa hc vt l, ho phn tch...
vi cc cng trnh nh tng hp c ure (Waller, 1828), vai tr ca dip lc trong quang hp
(Timirazep, 1843 1920), cht xc tc sinh hc ca Enzyme (Kirgop, Pasteur, Buchner)...
Sang th k XX nhiu pht minh v ho sinh c ghi nhn, nm 1926 Enzyme c bn cht
protein c xc nh, ATP c chit xut (Fiske v Subbarow, 1929), Hans Krebs (1937)
tm ra chu trnh acidxidric. Nm 1944, Avery, Maclesa v Mac Carty ch ra DNA l c s ca
s di truyn m u cho ho sinh di truyn. Kennedy v Lehninger (1950) tm ra s h hp t
bo sn sinh ra ATP ty th. Emil Fischer (1953) xc nh c ton b th t cc acid
amin trong cu trc bc I ca Insuline. Jemes Watson v Francis Crick (1954) tm ra cu
trc ca DNA. Nm 1961 Nirenberg v Matthei tm ra c chui poli U m ho cho Phe.
Song song vi vic tm ra cu to, vai tr v thnh phn ho hc ca s sng, ho sinh
cng khm ph c nhiu c ch ho hc c th ca tng khu quan trng nht trong qu
trnh trao i vt cht ca c th nh s h hp t bo, hot ng xc tc ca Enzyme, c ch
quang hp ca cy xanh, c ch tiu ho hp thu ng vt, c ch vn chuyn qua mng,
Cng nhng nm 60 ca th k XX Jacob v Monod tm ra s iu ho gen tng hp
protein v mt lot cc qu trnh sinh tng hp purin, acid amin, glucid, lipid ln lt c
sng t... Ngy nay vi s hon thin v k thut xc nh trnh t DNA v vic p dng t
ng ho v tin hc ho cho php gii m ton b th gen (genome) ca nhiu loi sinh
vt.
Ho sinh c vai tr quan trng trong ton b lnh vc pht trin sinh hc. Nh s pht
trin nhanh chng v nhng pht kin do ho sinh mang li m nhiu cuc cch mng
trong sinh hc bng n, gii quyt c nhiu vn ln cho yu cu ca con ngi
nh vn bnh tt ca con ngi v vt nui, vn gy t bin gen to nn hng lot
cy trng c tnh khng su bnh, c nng sut t bin gii quyt vn lng thc v
thc phm.
Ho sinh gi vai tr l cng c quan trng trong s pht trin ca sinh hc phn t v
hng lot cc ngnh ho sinh ra i nh ho sinh min dch, cng ngh ho sinh, ho sinh lm
sng...
Ho sinh cng l c s ca hng lot cc ngnh nh di truyn hc, dc hc, nhn v
to ging gia sc, dinh dng hc...
Sinh vt bin i gen hay l sinh vt chuyn gen (genetically modified organisms -
GMO) l mt bn anh hng ca (epic event) ca thi i v c mt ngha v cng to ln
trong lnh vc Sinh hc. Ngoi tnh chnh xc trong vic thm c tnh mi, s chuyn gen
hay s bin np gen cn cho php xo b ranh gii gia cc ging, loi ngha l vt qua
c hng ro t nhin trong cng tc to ging. y l mt vn cha tng c trong
lch s ng dng cc nghin cu Ho sinh hc.
Trong khun kh ca ngnh chn nui-th y, nhng kin thc m ho sinh mang li s
gip cho nhng nh chn nui v bc s th y khng nhng hiu bit c bn v hin tng
sng, bn cht ca qu trnh trao i vt cht trong c th, c ch v nhng nguyn nhn gy
nn bnh tt... t c th ch ng xut cc bin php tc ng nhm tng nng sut
v cht lng cc sn phm tht, sa, trng ng thi c bin php phng chng bnh cho vt
nui nng cao c hiu qu trong ngnh.

CHNG I
CU TRC V CHC NNG CA PROTEIN
1. khi nim v Chc nng ca protein.
1.1. Khi nim: Protein - i t ch Proteios ca Hy Lp ngha l "tm quan trng s
mt". Mt t ca Jns J. Berselius nm 1938 nhn mnh tm quan trng ca nhng phn
t ny.
V mt ho hc: Protein l mt polyme t nhin c cu to t cc monome l cc
acid amin.
V mt sinh hc: Protein l cht mang s sng. iu ny c Angel vit: S sng
l phng thc tn ti ca cc th protein v phng thc tn ti ny, v thc cht, l s i
mi thng xuyn ca cc cu t ho hc trong nhng th protein ny. Tht vy xt v cc
mt th hin ca s sng, chng ta u gp s tham gia ca protein nh s di chuyn trong
khng gian ca sinh vt l nh chc nng co dn ca protein c dng si, dng cu trong t c
l miozin v actin. S tiu ho, chuyn ho cc cht l nh cc protein enzyme. S t v
ca c th l nh protein loi bch cu, cc khng th...
Protein c trong tt c cc loi t bo vi t l khc nhau (% so vi khi lng vt cht
kh): la: 6-12, ng: 9-13, u tng: 29-50, gan: 57, xng: 28, c vn: 80...
1.2. Chc nng ca protein: Protein gi vai tr rt quan trng trong tt c cc qu
trnh sinh hc. ngha ng k ca chng c th hin qua cc chc nng sau y:
To hnh: Protein l thnh phn cu to ca cc t bo, k t siu khun n cc t bo
c nhn, cc m, cc sinh dch...
Xc tc sinh hc: l vai tr ca cc enzyme-mt loi protein c bit, di tc dng
ca chng, gip cho cc phn ng ho sinh hc xy ra.
iu ho chuyn ho: l cc protein hormone, gip cho cc phn ng trong t bo
xy ra ng chiu hng, ng cng m c th i hi.
Vn chuyn cc cht: V d Hb vn chuyn kh, Transferin vn chuyn st, Xytocrom
vn chuyn in t...
Chc nng co dui, vn ng: s vn ng ca c th l nh chc nng co dn ca
protein miozin v actin trong t c
Chc nng bo v c th: l nh cc khng th, cc bch cu. Cc khng th l cc
protein c hiu cao, n nhn bit v kt hp vi cc cht l nh virus, vi khun v cc t bo
t cc c th khc. V th protein gi mt vai tr sinh t trong vic phn bit gia mnh (self)
v khng phi mnh (nonself).
Tr gip c hc (Mechanical support). S ko cng ca da v xng l do collagen-
mt protein si
Pht xung v vn chuyn cc xung thn kinh. S p ng ca cc t bo thn kinh i
vi mt kch thch c hiu c thc hin qua trung gian cc protein tip nhn (Receptor).
Chng hn nh Rhodopsin l mt protein nhy cm vi nh sng trong cc t bo hnh que
vng mc. Cc protein Receptor cng c th c to ra bi cc phn t nh c hiu chng
hn nh Acetylcholine, n p ng cho s vn chuyn xung thn kinh cc synaps (khong
khng gia t bo thn kinh v cc cc m bo khc).
Kim sot s sinh trng v bit ho. S kim sot thng tin di truyn l cn thit
sinh trng v bit ho c trt t ca t bo. Ch c mt phn nh genome ca mt t bo l
c biu hin mt thi im no . vi khun, cc protein km hm l cc yu t kim
sot quan trng cc on c hiu "im lng" ca DNA ca mt t bo. cc c th c t chc
cao hn, s sinh trng v bit ho c kim sot bi cc protein yu t sinh trng. Chng
hn, yu t sinh trng thn kinh hng dn s hnh thnh mng li neuron. Hot tnh ca
cc t bo khc nhau trong cc c th a t bo c iu phi bi cc hormone. Chng hn
nh Insuline v hormone tuyn gip u l protein. Nh vy, protein hot ng trong cc t
bo nh l cc cm th quan (sensor) kim sot dng nng lng v cc qu trnh khc.
Cung cp nng lng: khi b phn gii 1 gam protein cung cp cho c th 4,1 kcal.
2. Cu to ca protein
Protein c cu to t cc nguyn t ho hc ph bin trong t nhin v theo mt t l
l (% khi lng protein):
C: 50-54%; O: 20-23%; H: 6-7%; N 16%. Ngoi ra cn c S, P, Fe,...
protein cu trc l c s ca chc nng, nn vic tm hiu v cu trc ca chng l
vn s mt. c rt nhiu cng trnh nghin cu v t cng c hng lot cc phng
php, phng tin v i i vi chng l hng lot cc pht hin mi trong cu trc ca
protein nh cu trc ca cc hormone, cc enzyme, cc khng th v c bit l cu trc
DNA...
Trc ht phi hiu c n v cu to nn mi loi protein l cc acid amin.
2.1. Acid amin- n v c bn cu to nn protein
2.1.1. nh ngha
Acid amin-n v c bn cu to nn protein, l nhng monome to nn cht polyme
protein. Cng thc chung ca acid amin l:
R

CH

NH
2
COOH
Trong cu to ca acid amin ta thy c mt nhm carboxyl mang tnh acid, mt nhm
amin mang tnh kim nm v tr Carbon (nguyn t Carbon c tn l bi v n ng k
cn nhm Carboxyl) nn cn c tn l -aminoacid, mt nguyn t Hydrogen v mt nhm R
c bn cht khc nhau. Nhm R c biu th nh l mt chui bn. Gc R khc nhau v to
nn cc acid amin khc nhau. Trong t nhin ngi ta tm c 250 loi acid amin nhng
protein trong c th sinh vt mc d khc nhau cng ch cha trong s 20 loi acid amin nht
nh m thi.
Cc acid amin trong dung dch pH trung tnh ch yu dng lng cc (Zwidterions)
hn l dng cc phn t khng ion ho. Trong dng lng cc ca acid amin th nhm amin
dng (-NH
3
+
) v nhm Carboxyl b phn ly (- COO
-
). Trng thi ion ho ca mt acid amin
thay i theo pH. Trong dung dch acid (pH =1) nhm Carboxyl khng b ion ho (- COOH)
v nhm amin li b ion ho (- NH
3
+
).
C COOH
NH
2
R
H C COO-
NH
3
+
R
H
(Dng khng Ion ho) (Dng Ion lng cc hoc Zwidterion)
Trong dung dch kim (pH =11), nhm Carboxyl b ion ho (- COO
-
) v nhm amin li
khng b ion ho (-NH
2
). i vi Glycine, pK ca nhm Carboxyl l 2,3 v ca nhm amin l
9,6. Ni mt cch khc, l im gia ca s ion ho th nht pH 2,3 v s ion ho th hai
pH 9,6.
Khi t din ca 4 nhm bao quanh nguyn t carbon to nn hot tnh quang hc
trn cc acid amin. Hai dng hnh nh i din qua gng c gi l ng phn quay cc
tri L v ng phn quay cc phi D. Ch nhng L acid amin mi tham gia cu trc Protein.
C 20 loi chui bn khc nhau v kch thc, hnh dng, din tch, kh nng lin kt
Hydrogen cng nh tnh phn ng ho hc thng thy cc protein. Tht vy, cc protein
trong tt c cc mu t vi khun ti ngi u c cu trc t cng mt b 20 acid amin.
Nhng chc nng quan trng ca protein l do tnh a dng v s linh hot ca 20 loi acid
amin ny. Chng ta s kho st nhng phng thc m iu c bn ny to nn cu trc
khng gian 3 chiu phc tp cho protein c th thc hin c nhiu qu trnh sinh hc.
n gin nht l glycine, n c ng mt nguyn t Hydrogen chui bn (Hnh 1.1).
Tip l Alanine, c mt nhm methyl. Cc chui bn hydrat carbon ln hn (3 v 4 C ) c
valine, leucine v isoleucine. Nhng chui bn ln hn ny l k nc (Hydrophobic) tc l
n ght nc v thch cm li. Cu trc 3 chiu ca cc protein ho tan trong nc c n
nh bi s cm li ca cc chui bn k nc. Hnh dng v kch thc ca cc chui bn
hydrat carbon ny (Hnh 1.1) lm cho chng c th bao vi nhau to nn cu trc c cng
vi cc l.

Hnh 1.1: Cng thc ca cc acid amin c chui bn bo
Proline cng c mt chui bn nhng khc vi chui bn ca cc thnh vin khc ca
acid amin l n gn c vi nguyn t nidrogen v c nguyn t carbon . Cu trc chu trnh
c to thnh (Hnh 1.2) nh hng ng k n kin to protein. Proline thng thy
nhng ch tht nt ca chui protein cun, v khng ght nc.

HN
C OH
O

Proline (Pro, P)
Hnh 1.2. Cu trc phn t Proline
3 acid amin c chui bn thm (Hnh 1..3) l Phenylalanine nh tn ca n ch r,
c cha mt vng phenyl gn vi mt nhm methylene (- CH
2
-). Vng thm ca Tyrosine
cha mt nhm Hydroxyl to cho Tyrosine t k nc hn so vi Phenylalanine. Tuy nhin,
nhm Hydroxyl ny c tnh phn ng ngc li vi cc chui bn tr ca cc amin acid khc.
Tryptophan c mt vng indole ni vi mt nhm methylene; chui bn ny c mt nguyn
t nidrogen thm vo cc nguyn t carbon v hydrogen. Phenylalanine v Tryptophan k
nc cao. Vng thm ca Phenylalanine, Tryptophan v Tyrosine c cha my in tr
khng nh v (delocalized) lm cho chng tng tc c vi h thng khc v vi cc
in t vn chuyn.

Nguyn t lu hunh c chui bn ca 2 -aminoacid (Hnh 1.4). Cystein cha mt
nhm sulfhydryl (- SH) v Methionine cha mt nguyn t lu hunh trong lin kt Thioester
(- S - CH
3
). C 2 chui bn cha lu hunh u ght nc. Nhm sulfhydryl ca Cystein c
tnh phn ng cao. Cystein gi mt vai tr c bit trong cu hnh ca mt s protein bng
cch to cc lin kt disulfide.
Hnh 1.4: Cc acid amin cha lu hunh.
Hai acid amin Serine v Threonine c cha cc nhm Hydroxyl (Hnh 1.5). Nhm
Hydroxyl trn Serine v Threonine lm cho chng a nc hn v c tnh phn ng hn
Alanine v Valine. Threonine cng ging nh Isoleucine c cha 2 trung tm bt i. Tt c
cc acid amin khc trong b c bn 20 tr glycine u c 1 trung tm bt i (nguyn t
carbon ). Glycine l cht duy nht (unique) bt hot quang hc.
Hnh 1.3: Cc acid amin thm.
Hnh 1.5: Cc acid amin cha nhm OH.
Cc acid amin c chui bn rt phn cc v lm chng a nc l Histidine, Lysine v
Arginine. Lysine v Arginine tch in dng pH trung tnh. Histidine c th khng tch
in hay tch in dng, tu thuc vo mi trng ca n. Histidine thng thy cc v tr
hot ho ca Enzyme, vng imidazole c th chuyn i gia cc trng thi xc tc b
gy cc lin kt.
Nhng acid amin kim c ghi trong hnh (1.6). Cc chui bn ca Arginine v Lysine
l di nht trong s 20 acid amin
Hnh 1.6: Cc acid amin kim tnh.
Cc acid amin cha chui bn acid l Aspartic v glutamic. Cc acid amin ny thng
gi l Aspartate v glutamate nhn mnh rng chui bn ca chng gn nh lun lun tch
in m iu kin pH sinh l (Hnh 1.7). Nhng dn xut khng tch in ca glutamate v
aspartate l glutamine v asparagine.
H
2
N CH C
CH
2
OH
O
C
OH
O
Axit Aspartic
H
2
N CH C
CH
2
OH
O
CH
2
C
OH
O
Axit Glutamic
H
2
N CH C
CH
2
OH
O
C
NH
2
O
Asparagin
H
2
N CH C
CH
2
OH
O
CH
2
C
NH
2
O
Glutamin
Hnh1.7: Cc acid amin c tnh acid v cc amide ca chng.
Ngoi ra cn 2 acid amin c chui bn l nhm k nc v c cha lu hunh l Nor
leucin v Cystin l dn xut ca Leucin v Cystein
CH
3
-CH
2
-CH
2
-CH
2
-CH- COOH CH
2
- S S - CH
2

NH
2
CH - NH
2
CH - NH
2

COOH COOH
Hnh 1.8. Cu trc phn t Nor leuxin v Cystin

Gi tr pK c trng v cn bng i vi s ion ho chui bn ca Arginine, Lysine,
Histidine, Aspartic v Acid glutamic, Cysteine v Tyrosine c ghi trong bng (1.1). Hai
nhm khc trong protein: nhm cui amin ( amin terminal) v nhm cui carboxyl (
carboxyl terminal) c th b ion ho cng c ghi trong bng ny.
Cc acid amin thng c k hiu hoc bng 3 ch vit tt hoc mt ch tng trng
d dng trong thng tin (bng 1.2).
Vit tt ca cc acid amin l 3 ch u tin tn acid amin tr trng hp Acid glutamic
(Glu), Acid apartic (Asp), Asparagin (Asn), Glutamine (Gln) v Isoleucine (Ile), Nor leucin
(Nor leu). Nhng tng trng ca mt s t acid amin l ch u tin tn acid amin (tc l G
cho Glycine v L cho Leucine).
2.1.2. Phn loi acid amin.
Phn loi theo ho hc: lin kt thng, lin kt vng; trung tnh, acid, base.
Phn loi theo sinh l (gi tr dinh dng): acid amin l nhng cht dinh dng cc k
quan trng i c th, khi ngi ta ni n thc n cn c protein tc l cn c cc acid amin.
c th ng vt cao ng (ngi v gia sc) kh nng t tng hp acid amin b hn ch,
trong s 20 acid amin cn thit tng hp protein th nhng ng vt ch tng hp c
trn di 10 loi. Nhng acid amin m c th khng t tng hp c ngi ta gi l "acid
amin cn thit", cn nhng acid amin c th t tng hp c c gi l "acid amin khng
cn thit". Do kh nng ca mi loi ng vt khc nhau nn s "acid amin cn thit" cng
khc nhau, thng thng gm 9 loi sau: Tre, Met, Val, Leu, Ileu, Lyz, Phe, Try, His. Cc
acid amin cn thit ny cn ph thuc vo la tui v d g con li cn Gly v Arg, khi
trng thnh th li khng cn na v chng t tng hp c.
Acid amin trong c th dng ng phn quay cc tri (dng L)
2.2. Cu trc bc I ca protein
2.2.1. nh ngha: y l cch lin kt gia cc acid amin li vi nhau bng lin kt
peptide to nn chui peptide:

- C - N -

O H
Lin kt peptide l lin kt hnh thnh bi nhm nh chc carboxyl ca acid amin ny
vi nhm nh chc amin ca acid amin bn cnh. y l lin kt ng ho tr nn rt bn
vng, ph v lin kt ny, trong phng th nghim ngi ta phi dng nhng tc nhn
mnh nh acid HCl, H
2
SO
4
... vi nng 4-6 N un nhit 102
0
C ko di 24 gi.
c tnh ni bt ca protein l chng c cu trc 3 chiu. Vo nhng nm cui 1930,
Linus Pauling v Robert Corey bt u cc nghin cu cc cu trc ca cc acid amin v
peptide. Mc ch ca h l bit c khong cch v cc gc lin kt tiu chun ca cc acid
Bng 1.1 v 1.2. Gi tr pK ca cc nhm Ion ho v vit tt ca cc acid amin
amin v ri dng nhng thng tin ny d on cu trc ca protein. Mt trong s cc pht
kin quan trng l n v peptide cng v phng (Hnh1.9). Hydrogen ca nhm amin thay
th hu nh lun lun dng Trans (i nghch) vi oxy ca nhm carbonyl ch tr lin kt
peptide X-pro (X l gc bt k), n c th l cis (cng mt pha) hoc Trans. Lin kt gia
nguyn t carbon carbonyl v nguyn t Nidrogen ca n v peptide l khng t do c th
quay c bi v lin kt ny c c tnh ring.
Chiu di ca lin kt ny l 1,32 A
0
n nm gia chiu di lin kt ca lin kt n (-N
(1,46 A
0
) v lin kt i (=N (1,51 A
0
). Ngc li, lin kt gia nguyn t Carbon v
nguyn t Carbon Carbonyl li l lin kt n tht s. Lin kt gia nguyn t Carbon v
nguyn t Nidrogen peptide cng l mt lin kt n thun khit. Cui cng, c mt mc
ln v s t do quay xung quanh nhng lin kt ny pha n v peptide cng (Hnh 1.9).
cng ca lin kt peptide to cho protein c dng 3 chiu xc nh. S t do quay pha
n v peptide cng c tm quan trng tng ng bi v n cho php protein cun li theo
nhiu cch.
Angstrom (A) - n v o chiu di bng 10
-10
met. 1 A
0
= 10
-10m
= 10
-8
cm = 10
-
m =
10
-1
nm. Anders J. Angstrom (1814 - 1874)
Hnh1.9. Cu trc mt n v peptide.
2.2.2. c im ca cu trc bc I: c 2 dc im quan trng l:
Th t sp xp trc sau ca acid amin trong chui. V d: c 3 loi: Val, Tre, Lyz s
c cc cch sp xp sau:
Val - Tre - Lyz, Tre - Lyz - Val, Lyz - Tre - Val, Val - Lyz - Tre, Tre - Val - Lyz,
Lyz - Val - Tre
Nh vy c 6 kiu v quy lut l 3! = 1.2.3 = 6 kiu v to nn 6 loi peptide khc nhau.
Vy vi 20 loi acid amin th s c 20! v s to ra s lng cc loi protein khc nhau l rt
ln. Chnh nh kh nng sp xp ht sc phong ph ny ca cc acid amin trong chui
peptide m tuy ch c 20 loi acid amin ta thy th gii sinh vt ht sc a dng.
Trong chui, u chui bao gi cng c nhm amin t do, cui chui c nhm carboxyl
t do.
S lng cc acid amin trong chui lm cho chui peptide di ngn khc nhau: 2 acid
amin gi l i peptide, 3 gi l tri peptide, 4-10 gi l olygopeptide v >10 gi l polypeptide.
Khi lng phn t ca chui peptide ph thuc vo iu ny. Trung bnh mi chui c
khong 150 acid amin v d Insuline c 51 acid amin, glucagon c 19 acid amin...
S khc nhau ca cc protein v cu trc bc I to nn tnh c trng sinh hc ca
protein t quyt nh c tnh, tnh trng ca sinh vt. Tnh c trng ny ring cho tng
loi protein v c di truyn rt cht ch qua nhiu th h (c m ho trong DNA)
2.3. Cu trc bc II ca protein
2.3.1. nh ngha: L cch xon gn li ca chui peptide, to cho chui peptide nhng
on xon kiu xon hay gp np .
Nm 1951 Linus Pauling v Robert Corey gi nh c 2 cu trc polypeptide l xon
v np gp . Xon l mt cu trc ging nh mt ci gy. Chui polypeptide lin kt chnh
cun cht li to nn phn bn trong ca gy, cn cc chui bn tri rng ra ngoi trong mt
hnh xon (Hnh 1.10). Xon c n nh bi lin kt hydrogen gia cc nhm NH v CO
ca chui chnh. Nhm CO ca mi acid amin to lin kt Hydrogen vi nhm NH ca acid
amin cch 4 gc v pha trc (Hnh1.10). Trong xon , nhm CO ca gc n lin kt
Hydrogen vi nhm NH ca gc (n + 4). Nh vy tt c cc nhm CO v NH ca chui chnh
u c lin kt Hydrogen. Gc n cch gc kia 1,5 A
0
dc theo trc xon v gc quay l
100 gm 3,6 gc acid amin cho mt chu k xon. Nh vy cc amin acid c tri rng li
rt gn v mt khng gian trong xon . Khong cch ca xon l 1,5 A
0
v khong cch
trong mt chu k (3,6 gc) l 5,4 A
0
.
Vng xon c th l bn phi (Clockwise) thun chiu kim ng h hoc bn tri
(counter clockwise) i kim ng h. Cc xon ca protein l quay phi. Mc xon ca
protein rt rng t 0 ti gn 100%. V d Enzyme tiu ho chymotrypsin khng c xon .
Ngc li myoglobin v hemoglobin c ti 75 % l xon . Xon n thng c chiu di
nh hn 45 A
0
. Tuy nhin, hai hay nhiu xon c th an vi nhau to nn nhng cu
trc rt n nh n c th di n 1000 A
0
(100nm hay 0,1m) hoc hn. Nhng xon
(Hnh 1.11) thy Myosin v Tropomyosin ca c, fibrin trong cc cc mu v keratin trong
tc. Cc cp xon trong nhng protein ny gi vai tr c hc trong vic hnh thnh nhng b
rn chc ca cc si nh trong lng ln.
Cu trc xon c Pauling v Corey suy din khong 10 nm trc y khi h quan
st qua cu trc tia X ca Myoglobin. S gii thch v cu trc ca xon l mt bc ngot
trong sinh hc phn t bi v n chng minh c rng cu trc ca mt chui polypeptide c
th c d on nu bn cht cc thnh phn ca n c hiu mt cch chnh xc v
tun theo mt nguyn tc nghim ngt.
Pauling v Corey cng pht hin mt cu trc khc l np gp (gi l bi v n
c xc nh l cu trc th hai cn xon l th nht). Np gp khc nhiu so vi xon
. Mt chui polypeptide trong np gp gi l mt dy (si) hu nh c dui ra hon
ton ch khng cun cht nh trong xon . Dng np gp c n nh bi lin kt di
sunfid (- s - s -) lin kt ny c hnh thnh t 2 nhm sulfihydryl (-SH) ca 2 acid amin Cys
khi chng gn nhau trong khng gian. Dng gp np c bc xon tha thng c
nhng protein dng si nh keratin lng, tc, sng, mng.
Khong cch trc gia cc acid amin k cn l 3,5 A
0
, ngc li xon l 1,5 A
0
.
Mt sai khc na l np gp c lm n nh bi cc lin kt Hydrogen gia cc nhm NH
v CO trong cc si polypeptide khc nhau, trong khi xon , lin kt Hydrogen l gia
cc nhm NH v CO trong cng mt si. Nhng chui k cn trong np gp c th chy
cng mt hng (np song song) hoc cc hng i nghch (np i song song) (hnh
1.12), v d nh cc si t bao gm ch yu cc np gp . Gp l mt cu trc c trong
nhiu protein. Nhng n v cu trc ny thng thng bao gm t 2 n 5 si song song
hoc i song song..
Hnh 1.11. Siu xon .
Hnh 1.12. Cu trc i . Cc si mi to thnh chy theo nhng hng ngc li.
2.4. Cu trc bc III ca protein
2.4.1. nh ngha: L cch xp xp gn li trong khng gian ca chui peptide khi
c cu trc bc II.
2.4.2. Cc lc ni n nh cu trc bc III:
Lc disulfid - S - S - lin kt ny c hnh thnh t 2 nhm sulfihydryl (-SH ) ca 2
acid amin Cys khi chng gn nhau trong khng gian khong 2 ln ng knh phn t. y
l lin kt ng ho tr nn tng i bn vng (W = 4-5Kcal/mol), tuy nhin s lng lin
Hnh 1.10. Xon
kt ny t (4-6 lin kt trong 1 phn t) nn tc dng n nh cu trc bc III l khng gi vai
tr quyt nh.
Mt s protein c cha lin kt disulfide. S lin kt cho gia cc chui hoc gia cc
b phn ca mt chui c to ra bi s oxy ho ca cc gc Cystein disulfide to thnh
lin kt disulfide (hnh 1.13). Cc protein trong ni bo thng thiu lin kt disulfide, trong
khi cc protein ngoi bo thng cha mt vi lin kt ny. Dn xut ca nhng lin kt
cho khng lu hunh ca cc chui bn ca lysine cng c mt trong mt s protein. Chng
hn nh, cc si collagen m lin kt lm cho m ny vng chc, hay l cc si ng mu
Hnh1.13 Cu Disulfide (-S-S-)c hnh thnh t cc nhm SH ca Cys trong
Insuline
C th ni cu trc bc III ca protein ch yu n nh c l nh mt lot cc lin kt
ph, c lc ni yu, nhng c mt khp mi ni trong phn t protein. l:
Lin kt Hydro > N....H... N <. y l lin kt xut hin trong trng hp cht c hin
tng phn cc, gia hai nhm mang in tch m c khong cch 2-3 A
0
c hydro gia
Lin kt ca cc nhm k nc (nhm khng a nc, ch cha C, H nh: Val, Leu...)
nhm ny c tnh y nc v b nc y, trong dung dch keo khi chng gn nhau s to
thnh mt m to nn lc lin kt.
Lc Valderval (lc hp dn vi m): l lc ni xut hin gia cc nhm phn t khi
chng nm gn nhau mt khong cch bng 1,5-2 ln ng knh phn t.
Lin kt ion xut hin gia cc acid amin cn d nhm cacboxyl (-COOH) v nhm
amin (-NH
2
) trong dung dch chng phn ly thnh cc ion COO
-
v NH
3
+
.
Lin kt peptide xut hin gia cc acid amin cn d nhm -COOH v -NH
2
khi chng
gn nhau (s lng lin kt ny cng rt t). ( Hnh 1.14)
c im ca cc lin kt ny l nng lng lin kt thp, n l lin kt yu nhng n
c mt khp ni trong phn t protein cho nn tc dng n nh cu trc ca n l rt ln,
ng thi do yu nn d chu nh hng tc dng ca mi trng (t
0
v pH).
2.4.3. H qu ca cu trc bc III:
Trong cu trc bc III c mt iu c ngha quyt nh i vi hot tnh ca protein
l thng qua vic hnh thnh cu trc bc III trong phn t protein hnh thnh nn cc trung
tm hot ng:
Trung tm hot ng l yu t bt buc phi c cc protein chc nng (enzyme, khng
th...), l ni tip xc gia protein vi i tng tc ng, l ni thc hin cc phn ng ho
sinh ca protein.
Trung tm hot ng c hnh thnh t mt s acid amin bnh thng nm xa nhau
dc theo chui peptide, nhng nh c cu trc bc III m chng c gn nhau trong khng
gian phi hp vi nhau thc hin chc nng ca protein nh trypsinogen ( Hnh 1.15)
Hnh 1.15: Cu trc ca trypsinogen
Hnh 1.14. M hnh cc lin kt trong cu trc bc III ca protein
Cc gc acid amin thng tham gia vo trung tm hot ng l: Cys vi nhm -SH, Ser,
Tyr, Tre vi nhm - OH; Lyz, Arg vi nhm -NH
2
, Glu, Asp vi nhm COOH, His vi
nhm imidazon.
C th ni trung tm hot ng ca protein c c l nh c cu trc bc III v n nh
c l nh s n nh ca cu trc bc III. V l do trn tt c nhng yu t g nh ti cc
lin kt duy tr cu trc bc III u nh hng ti trung tm hot ng, nh hng ny c th
tch cc hoc tiu cc i vi chc nng ca protein, nu l nh hng tch cc lm cho
protein thc hin chc nng thun li hn ta gi l hin tng hot ho protein, ngc li
nu l nh hng tiu cc lm ri lon mo m cu trc bc III, lm cho protein hot ng
yu i, thm ch khng hot ng, ngi ta gi l hin tng c ch hoc lm t lit chc
nng ca protein.
Nhng yu t nh hng ti trung tm hot ng l nhng yu t nh hng ti cc lin
kt trong cu trc bc III t nh hng ti hot tnh ca protein. Trong c th ng vt cc
yu t l t
0
v pH. ng vt, nhit n nh ca c th c nhng tr s nht nh
(ngi: 36-37
0
C, tru b 37-38
0
C, gia cm 39-41
0
C...), mi mt m bo tu theo chc nng
m c pH ring ca mnh. Nhit v pH l iu kin ti u ca nhng protein chc
nng.
2.5. Cu trc bc IV ca protein.
2.5.1. nh ngha: L cch tp hp, kt hp vi nhau ca mt s tiu phn protein
c cu trc bc III to nn nhng t hp phc tp v qua to cho phn t protein c nhng
c tnh mi. V d:
Hb c 4 tiu phn lin kt vi nhau bng cu trc bc IV theo hnh t din u.
Phn t enzyme Phosphorylase thc hin phn ng phn gii glycogen thnh glucose
trong chuyn ho ng, khi trng thi dime (dng phosphorylase b) chng khng c hot
lc, khi chuyn sang dng tetrame (dng phosphorylase a) th chng c hot lc:
O - O
4ATP
4ADP
O - O
O - O
P
P
P
P
Protein-kinase
Phosphorylase b dng dime Phosphorylase a dng tetrame
2.5.2. ngha: y l cch iu ho hot tnh ca protein ng thi tit kim c
nguyn liu.
3. Ct v sa i protein to nn cc kh nng mi.
Nhiu trong s 20 acid amin c th b thay i sau khi chui polypeptide c tng
hp nn lm tng thm kh nng ca protein. V d cc amin cht ca nhiu protein
acetyl ho, iu lm cho protein tng s khng li s phn gii. cc collagen tng hp
mi, nhiu gc protein hydroxyl ho to hydroxyproline (Hnh 1.16). Nhng nhm
hydroxyl c thm vo lm n nh si collagen. ngha sinh hc ca s sa i ny
c dn ra trong bnh thiu vitamin C (Scurvy) nguyn nhn l do s hydroxyl ho khng
y ca collagen v thiu vitamin C. Cc amin acid chuyn bit khc cng c to ra nh
- carboxyglutamate. Khi thiu vitamin K, s carboxyl ho khng ca glutamate trong
prothrombin, mt nhm protein ng cc do dn ti s xut huyt. Hu ht cc protein,
chng hn nh cc khng th c tit ra bi cc t bo i hi phi c n v carbohydrate
trn cc gc asparagine c hiu. Vic thm carbohydrate vo lm cho protein a nc hn.
Ngc li, mt protein c th tr nn ght nc hn nu thm mt acid bo vo nhm -amin
hoc mt nhm sulfhydryl ca Cystein.
Nhiu Hormone, chng hn nh Adrenalin, lm thay i hot tnh ca nhiu Enzyme
do s kch thch phosphoryl ho ca acid amin hydroxyl l serine v Threonine.
Phosphoserine v phosphothreonine l cc acid amin c sa i thng xuyn nht trong
cc protein. Cc yu t sinh trng tc ng bng cch to nn s phosphoryl ho nhm
hydroxyl ca Tyrosine to nn phosphoTyrosine. Cc nhm phosphate trn 3 acid amin
sa i ny c th b loi i, lm cho chng c th tc ng nh s chuyn i nghch trong
s iu ho cc qu trnh ca t bo. Tht vy, mt s gen sn sinh ung th (oncogene) tc
ng bng cch kch thch s phosphoryl ho d tha cc gc Tyrosine trn cc protein kim
sot s tng sinh ca t bo.
Hnh 1.16: S sa i cc gc acid amin mt s protein.
Nhiu protein b ct xn sau khi sinh tng hp. Chng hn nh cc Enzyme tiu ho
khi c tng hp, tin thn ca n l bt hot c th ct gi an ton tu. Sau khi c gii
phng vo ng tiu ho, nhng tin thn ny tr nn hot ho do ct i lin kt peptide.
Trong qu trnh ng mu, fibrinogen ho tan chuyn thnh fibrin khng ho tan cng do s
ct bt lin kt peptide. Nhiu hormone polypeptide chng hn nh adrenocorticotropin do s
ch nh ca mt protein tin thn. Cng ging nh vy, cc protein ca poliovirus c to
nn do s xn bt ca mt polyprotein tin thn ln hn. Mt vi protein ch cht ca Virus-
1 (HIV-1) gy nn AIDS l do s ct xn c hiu ca mt tin thn di hn.
Cc chui Polypeptide c th o hng do s quay gp. Nhiu protein c hnh cu,
gn c s o hng trong cc chui polypeptide ca chng. Nhiu s i hng c hon
tt bi mt yu t cu trc gi l s i hng . Trong s quay ny nhm CO gc (n) lin
kt Hydrogen vi nhm NH ca gc (n + 3) (Hnh 1.17). Nh vy mt chui polypeptide c
th i hng mt cch bt ng. S i hng thng ni cc si i song song. N
cng c hiu nh l s i hng hay s b gp t ngt.
Xon Collagen c n nh bi Proline v Hydroxypoline.
Mt dng c bit ca xon c trong Collagen - thnh phn si chnh ca da, xng
gn, sn v rng. Nhng protein ngoi bo c cha 3 chui polypeptide xon. Mi chui di
1000 gc. Trnh t acid amin ca collagen rt iu ho: gn nh 1/3 gc l glycine, proline
chim 12%. Hn na collagene c cha 2 acid amin him gp l Hydroxyproline v
hydroxylusine. Trnh t glycine - Proline - Hydroxyproline (Gly - Pro - Hyp) cng thng
c ti din (Hnh 1.18).
Collagen l mt phn t hnh que di khong 3000 A
0
nhng ng knh ch 15 A
0
.
Ho tit xon 3 (Hnh1.18) hon ton khc vi xon . Lin kt Hydrogen c trong ni b
mt si. 3 dy cun li vi nhau to nn cp siu xon. Khong cch trc cho 1 gc trong siu
xon l 2,9 A
0
v c gn 3 gc cho mt chu trnh. 3 dy ny c lin kt Hydrogen vi nhau.
Cht cho Hydrogen l nhm NH peptide ca gc glycine v cht nhn hydrogen l nhm CO
cu cc chui khc. Nhm Hydroxyl ca cc gc Hydroxyproline cng tham gia trong lin kt
Hydrogen.
n by gi chng ta hiu ti sao glycine chim 1/3 v tr tri di hng nghn gc to
nn vng xon ca collagen. Pha bn trong ca cp dy 3 ny rt cht. V vy, ch c glycine
l c th va kht v tr bn trong ny. V c 3 gc cho mt chu trnh xon, cho nn phi c
1/3 gc trn mi dy l glycine.
Khi quan st si collagen ta thy c vn ngang, l cc phn t Tropocolagen cc
dy k nhau xp lch nhau 1/4 phn t. Trn cng mt dy, gia phn t Tropocollagen c
mt khp di 400 A
0
.
Hnh 1.17: o hng quay ca peptide.
Protein giu lin kt hydrogen. Nhng nhn t no xc nh cu trc 3 chiu ca
protein? Cc tng tc phn t trong cc h thng sinh hc u qua 3 nhn t trung gian: lin
kt tnh in, lin kt Hydrogen v lin kt Valderval. Chng ta cng thy lin kt
Hydrogen gia cc nhm NH v CO ca chui chnh to xon , np gp v cp
collagen. Trong thc t, cc chui bn ca 11 trong s 20 acid amin nn tng u c th tham
gia lin kt Hydrogen. V th chng ta ni cc acid amin ny c tim nng lin kt Hydrogen:
1. Cc chui bn ca Tryptophan v Arginine c th hot ng ch nh cht cho lin kt
Hydrogen (Hydrogen bond donor).
2. Cng ging nh chnh n v peptide, cc chui bn ca Asparagine, Glutanine v
Threonine hot ng nh nhng cht cho v nhn lin kt Hydrogen.
3..Kh nng lin kt Hydrogen ca Lysine (v nhm cui Amin), Aspartic v Acid
glutamic (v nhm cui Carboxyl), Tyrosine v Histidine thay i theo pH. Cc nhm ny c
th hot ng vi t cch l cht nhn cng nh cht cho trong mt thang pH xc nh v vi
t cch l cht nhn hoc cht cho (ch khng phi c hai) nhng pH khc nh Aspartate
v Glutamate trn hnh (1.19). Mu hnh lin kt Hydrogen ca cc gc c th ion ho ny l
ph thuc pH.

Hnh 1.18 Cu trc ca Collagen xon ba.
Nhm cho hydrogen ca tryptophan Nhm cho hydrogen ca Arginine
Hnh1.19: Cc nhm lin kt hydrogen ca mt s chui bn protein.
Protein ho tan trong nc cun li trong cc cu trc thch hp c cc li khng
phn cc.
Trnh t acid amin ca chui Collagen Cu trc mt chui Collagen xon ba
Nhng nghin cu tia X ch r chi tit cu trc 3 chiu ca trn 300 protein. Chng ta
bt u vi Myoglobuline, protein u tin c nhn nhn chi tit mc nguyn t.
Myoglobine, l cht d tr oxy c, n l mt chui polypeptide n vi 153 acid
amin, khi lng phn t l 18Kd. Myoglobine c kh nng gn vi oxy ph thuc vo s c
mt ca Hem, mt nhm prosthetic khng polypeptide bao gm protoporphyrin v mt
nguyn t st trung tm. Myoglobine l mt phn t cc k thch hp vi chc nng vn
chuyn O
2
. Kch thc ca n l 45 x 35 x 25A
0
. Cu trc bc 1 ca Myoglobine l cc xon
, phn t ny c 8 xon. Khong 70% chui chnh cun li trong cc xon v nhiu phn
cn li ca chui to thnh cc chu trnh gia cc xon. C 4 vng cha proline, c xu hng
lm ph v cc xon bi v n lm chng ngi khng gian bi mt vng 5 rn chc (rigid).
S cun li ca chui chnh Myoglobine cng ging nh cc protein khc, n l mt
phc hp v khng cn i. S tht ni bt l bn trong bao gm hu ht cc gc khng
phn cc nh Leucine, Valine, Methionine v Phenylalanine. Nhng gc phn cc nh
Aspartate, Glutamate, Lysine v Arginine khng c mt trong Myoglobine. Ring ch c vi
gc phn cc c mt pha trong l 2 Histidine gi vai tr c bit trong vic gn oxy ca
Hem. Mt khc, pha ngoi ca Myoglobine li cha c nhng gc phn cc v khng phn
cc. M hnh khng gian y cng ch r rng n c rt t khong trng bn trong.
S phn phi i nghch ca cc gc phn cc v khng phn cc vch r nhng
kha cnh c tnh cht cha kho ca kin trc protein. Trong mt mi trng nc, cc
protein cun li l do khuynh hng loi tr nc mnh m ca cc gc k nc. Cn phi
nhc li rng nc cu kt rt cao cn cc nhm k nc li n nh nhit ng hn khi t
bn trong phn t. Chui Polypeptide v th cun li mt cch t pht cho cc chui bn k
nc chm vo bn trong, nhng chui tch in phn cc th nm trn b mt. S phn ca
chui chnh i km vi chui bn k nc cng rt quan trng. B mt ca vic chn su mt
on ca chui chnh trong mt mi trng k nc l to cp tt c cc nhm NH v CO
bng lin kt Hydrogen. Cc cp i ny c hon thin trong xon hoc np gp . Lin
kt Valderval gia cc chui bn Hydrocarbon cng gp phn lm n nh cho protein. By
gi th chng ta hiu ti sao b 20 acid amin c cha mt vi acid amin khc nhau v hnh
dng v kch thc mt cch tinh t nh vy.
Ribonuclease, mt Enzyme tuyn tu phn gii RNA l mt v d v cc cch khc
nhau ca cun protein. Chui polypeptide n ny gm 124 gc cun li ch yu trong cc
dy . Ngc li, vi Myoglobine c cha cc xon nhng thiu cc dy . Ribonuclease
cng ging nh Myoglobine c cha bn trong cht khng phn cc cao v cun rt cht.
Enzyme ny c lm n nh xa hn bi 4 lin kt disulfide. Cu trc ca mt protein c th
c tng trng trong dng x to vi cc dy nh nhng mi tn rng cn xon nh
mt ng xon v nhng vng ni nh nhng si dy bn (string).
M hnh Ribonuclease (hnh 1.20) ca Richardson rt li ch cho vic th hin cc mi
lin quan ca cc yu t trong cc protein, c bit l cc protein ln v rt li cho vic xc
nh cc tit ho cu trc trong cc protein khc.
Nhng protein mng khng th thiu c, n tri trn cc mng sinh hc, c thit k
khc so vi cc protein ho tan trong dung dch nc. Barrier tnh thm ca mng c to
bi cc Lipide, chng l cc cht k nc mnh. Nh vy, phn protein mng tri trn vng
ny phi c u ngoi k nc, phn vn chuyn mng ca protein mng thng bao gm cc
b xon vi cc chui bn khng phn cc (chng hn nh Leucine v Phenylalanine)
chng hng ra ngoi b mt ca protein ny.
4. Bn mc cu trc ca protein.
Cu trc bc 1 l trnh t cc acid amin. Cu trc bc 2 l s sp xp khng gian ca cc
gc acid amin, gc n k gc kia trong trnh t thng. Xon v dy l cc thnh vin ca
cu trc bc 2. Cu trc bc 3 l s sp xp khng gian ca cc gc acid amin xa nhau v
m hnh ca lin kt disulfide v cc lin kt ph. Tuy nhin vic chn ra cu trc bc 2 hay
bc 3 ch l cm gic.
Cu trc bc 4 l s sp xp khng gian ca cc n v (Subunid) v bn cht tip xc
ca n. V d nh Hemoglobine, c cha 2 chui v 2 chui . Cc n v ny giao din
vi nhau trong mt Tetramer tham gia vo vn chuyn thng tin gia cc v tr gn xa i
vi O
2
, CO
2
v H.
Hnh 1.20. Phn t Ribonuclease
Nhng nghin cu v cu trc chc nng v s tin ho ca protein vch r tm quan
trng ca 2 mc khc na ca t chc. Cu trc siu bc 2 (Supersecondary Structure) ch
cm nhng cu trc bc 2, chng hn nh mt dy tch bit vi mt dy khc bi mt
xon thy nhiu protein. Ho tit ny c gi l n v (Hnh 1.21).
Mt s chui polypeptide cun li trong 2 hoc nhiu hn cc vng chc c (compact)
c th ni vi nhau bi nhng on co rn ca chui polypeptide cng ging nh cc qu l
trn mt cnh. Nhng n v hnh cu chc c ny gi l domain, c kch thc t khong
100 n 400 gc acid amin. Chng hn nh, chui L25 - Kd ca mt khng th cun li trong
2 domain (Hnh 1.21). Nhng n v hnh cu ny gn ci n vi ci kia, iu khin ngi
ta cho rng chng c xut hin do s nhn i ca mt gen nguyn thu. Mt nguyn tc
quan trng c pht hin t s phn tch gen v protein Eucaryote bc cao hn l Cc
domain protein thng c m ho bi cc phn tch bit ca gen gi l exon.
Nhng protein c nhiu chui polypeptide th c thm mc t chc cu trc. Mi chui
polypeptide trong nhng protein nh th gi l di n v ( Subunid ).
Hnh 1.21. Siu cu
trc bc 2 ca
protein
5. Th t cc acid amin chuyn ho cu trc khng gian ca protein
Chng ta hy xem xt mi quan h gia cc th t acid amin ca mt protein v cu
trc ca n t cng trnh kinh in ca Christian Anfinsen trn Ribonulease. l mt cht
sm c ch , Ribonuclease l mt chui polypeptide gm 124 gc acid amin, 4 lin kt
disulfide c th b ct i do vic kh chng vi mt thuc th nh -mercaptoethanol n s
hnh thnh disulfide hn hp vi chui bn Cystein (hnh 1..22).
Khi cho d nhiu -mercaptoethanol th cc disulfide hn hp cng b kh, sn phm
cui cng l 1 protein trong disulfide (Cystin) c chuyn hon ton thnh sulfhydryl
(Cysteine). Tuy nhin, ngi ra cng pht hin rng Ribonuclease 37C v pH 4 li khng
b kh bi -mercaptoethanol tr phi protein ny c x l vi cc thuc th nh urea hoc
guanidine hydrochloride. Mc du c ch tc ng ca cc tc nhn ny cha c r hon
ton, nhng r rng l chng lm ri lon cc tng tc khng ng ho tr. Hu ht cc
chui peptide u khng c cc lin kt cho tha nhn mt cu trc cun ngu nhin
trong urea 8M hoc Guanidine HCl 6M.
Khi Ribonuclease c x l vi -mercaptoethanol trong urea 8M th sn phm l mt
chui polypeptide cun li mt cch ngu nhin v b kh hon ton, n khng c hot tnh
Enzyme. Ni mt cch khc, Ribonuclease b bin tnh do s x l ny (hnh 1..23).
Sau Anfisen c nhng quan st c bit v Ribonuclease b bin tnh khi loi
tr urea v -mercaptoethanol bng thm tch th hot tnh Enzyme li c phc hi mt
cch chm chp. ng lnh hi c ngha ca s pht hin tnh c ny l: Sulfhydryl ca
cc Enzyme b bin tnh s b oxi ho bi khng kh v Enzyme ny li cun li mt cch
t pht trong dng hot ho xc tc. Nhng nghin cu chi tit sau ch ra rng hu nh
tt c hot tnh Enzyme gc (original) s c khi phc nu nhm sulfhydryl b oxi ho di
nhng iu kin thch hp (hnh 1..23). Tt c cc c tnh l ho ca Enzyme cun li phn
bit r rng vi Enzyme nguyn mu (native). Nhng th nghim ny ch ra rng thng tin
Hnh 1.22: S kh cu disulfide trong mt protein bng cch cho d tha thuc th
sulfhydryl (R-SH) chng hn nh -mercaptoethanol.
cn chuyn ho phc hp cu trc 3 chiu ca Ribonuclease nm trong cc th t acid
amin. Nhng nghin cu sau ny xc nh mt cch tng qut nguyn l trung tm ca
sinh hc phn t l th t chuyn ho cc cu trc ho hc. Mt kt qu khc thu c khi
Ribonuclease kh s b oxi ho khi urea 8M. Ch phm ny sau c thm tch
loi urea. Ribonuclease b ti oxi ho theo cch ny ch c hot tnh Enzyme 1%.
Hnh 1.23. S hon nguyn ca ribonuclease
Ti sao kt qu ca th nghim ny khc vi kt qu trong Ribonuclease b kh s
li ti oxi ho trong dung dch khng c urea? L do l to vng i disulfide khng ng
(wrong) phn t kh khi b ti oxi ho v c ti 105 cch ca 8 vng i Cystein hnh
thnh 4 disulfide; nhng ch c mt trong s cc hp cht ny l c hot tnh Enzyme. 104
vng i sai c tn l Ribonuclease "leo tro" (Scramble). Sau Anfinsen thy cc
Ribonuclease leo tro ny chuyn i mt cch t pht thnh Ribonuclease nguyn mu,
y hot tnh khi cho vo mt t -mercaptoethanol trong dung dch nc (hnh 1..23). -
mercaptoethanol c thm vo s xc tc s sp xp li ca cc vng i disulfide cho n
khi cu trc ban u c hon nguyn, thi gian mt khong 10 gi. Qu trnh ny c
thc hin hon ton bi vic lm gim nng lng t do nh cu trc "leo tro" chuyn
thnh cu trc ca Enzyme. Nh vy, dng ban u ca Ribonuclease l cu trc n nh nht
v nhit ng hc. Tuy nhin, iu quan trng l vic cun li ca nhiu Enzyme li c s
tr gip bi Enzyme, n xc tc t ti trng thi nng lng thp nht.
S ho hp nh th no ca tng tc trung gian to nn s chuyn ngc t dng
khng cun sang dng cun ca mt protein? Cu trc ca mt protein c th c suy lun
t cc th t acid amin ca n c khng? Nhng vn ny l trung tm ca ho sinh phn
t.
Anfinsen (1964) vit: Ci p vo ti gn y l ngi ta c th tht s thy c cc
th t ca mt phn t protein, v s cun li trong mt dng hnh hc chnh xc ging nh
mt hng ch vit p trong dng quy chun v s to mu vi bn cht cun li ca n,
to nn s ho hp vi chc nng sinh hc.
6. S gn c hiu v nhng thay i cu trc l c s ca tc ng protein
Bc u tin trong tc ng ca mt protein l vic gn ca n vi phn t khc.
Protein nh l mt lp cc i phn t c quyn v kh nng nhn bit v tng tc cao vi
cc phn t dn sut. V d nh Myoglobin gn cht vo mt nhm Hem khi chui
polypeptide ca n cun li phn no. Protein cng kt hp vi cc protein khc to nn
nhng s xp t th t cao chng hn nh nhng si co gin c. Vic gn cc phn t l
vo protein khng th c th lm cho s min dch phn bit c gia mnh v khng phi
mnh. Xa hn na l, s biu hin ca nhiu gen b kim sot bi vic gn ca protein lm
nhim v nhn dng cc th t DNA c hiu. Protein cng c kh nng tng tc mt cch
c hiu vi mt dy cc phn t v chng rt ti tnh trong vic hnh thnh cc b mt v cc
khe b cu. S tinh t ca cc chui bn trn nhng b mt ny v cc khe h c th lm cho
protein to c cc lin kt hydrogen, lin kt tnh in, lin kt Valderval vi cc phn t
khc.
Nh nhn mnh phn m u ca chng ny, hu ht tt c cc phn ng trong h
thng sinh hc u c xc tc bi nhng protein c gi l Enzyme. By gi chng ta s
nh gi mt cch chnh xc l ti sao protein li gi vai tr c quyn trong vic xc nh
mu hnh (pattern) ca cc vn chuyn ho hc hay kh nng xc tc ca cc protein i t kh
nng gn ca chng vi cc phn t c cht trong nhng hng chnh xc v n nh trong
trng thi qu (transidion) v s b gy cc lin kt ho hc. Nguyn l c bn ny c th
tnh c c th bng mt v d n gin v s xc tc Enzyme, s hydrat ho ca carbon
dioxide bi carbonic anhydrase
H
2
O + CO
2
CHO
3
-
+ H
+
Carbonic anhydrase lm tng tc phn ng ln trn 1.000.000 ln nh th no? Phn
kch thch tnh phn ng l do tc ng ca ion km, n phi hp cc nhm imidazol ca 3
gc histidine trong Enzyme ny. Ion km nh v y ca mt khe su chng 15A
0
di b
mt ca protein. Gn k l mt nhm ca gc nhn bit v gn carbon dioxide. Khi nc gn
vo ion km th n nhanh chng chuyn thnh ion hydroxide, l v tr chnh xc tn
cng vo phn t dioxide carbon gn tip vo n (hnh 1.24.). Ion km ny gip cho s nh
hng CO
2
cng nh cung cp mt lng ln OH
-
. Carbonic anhydrase cng ging nh
nhng Enzyme khc, n l mt cht xc tc cao bi v n a c cht vo s gn gi khng
gian v lm thch hp hng ca cc phn ng.
O
H
C
O
O
Zn++
His
His
His
O
-
Zn++
His
His
His
C O
O
H
Hnh 1.24. C ch phn ng ca carbon anhydrase. Ion hydroxide v carbon dioxide
c sp t mt cch chnh xc lm thun li cho vic hnh thnh bicarbonate bi s lin kt
ca chng vi Z
n
2+
.
S ti din khc ca xc tc l vic s dng cc nhm tch in phn cc c cht v
lm n nh trng thi qu .
.

Hnh 1.25. S tng
tc Allosteric
iu quan trng v ng ch nht l mt s protein c nhiu v tr gn, cc v tr ny
c s thng tin vi nhau. S thay i cu trc cm ng bi vic gn mt phn t vo mt v
tr trong mt protein y cc v tr lch ra xa trn 20A
0
. V th, protein c th c xy
dng hot ng nh nhng cu giao phn t (molecular swidch) tip nhn, hp nht v
truyn cc tn hiu. Nhiu protein c cha cc v tr iu ho gi l v tr allosteric kim sot
vic gn ca chng vi cc phn t khc v lm thay i tc phn ng ca chng (hnh
1.25). V d nh, vic gn oxygen vo nhm Hem ca hemoglobine l kt qu ca s thay i
vic gn H
+
v CO
2
cc v tr xa trong phn t protein.
S kim sot allosteric trung gian bi s thay i cu trc trong phn t protein l trung
tm ca s iu ho trao i cht. Trong h thn kinh, protein knh nhy cm vi a kch
thch hot ng nh cc cng, ging nh cng trong chip ca computer
Protein c 2 v tr gn c lin quan ti s thay i cu trc lm cho n c kh nng
chuyn i nng lng. Gi s mt protein c mt v tr xc tc cho s thu phn adenosine
triphosphate (ATP) thnh (ADP) l mt phn ng cho nng lng. S thay i t
Triphosphate ti Diphosphate cm ng s thay i v tr xc tc, chuyn v tr gn sang mt v
tr khc xa hn trn cng mt protein. Nh vy, enzyme vi chc nng nh nhng m t phn
t lm thay i nng lng lin kt ho hc trong s vn ng trc tip nh s co c
7. c tnh l ho ca protein
7.1. Protein tn ti sinh vt trng thi keo: Mi trng trng thi keo ca protein
l nc. Tiu chun ca h keo ph thuc vo kch thc ht ho tan (1-150m). c tnh ca
h keo l va c c tnh lng (tc phn ng nh mi trng lng) va c c tnh rn (c
hnh th nht nh).
Protein l keo a nc v protein mang nhng nhm a nc (-NH
2
, -COOH, -OH).
Keo protein c cc c tnh in hnh ca keo a nc nh: gy p sut thm thu thp (30-
40mmHg 0,03-0,04at); kh nng khuch tn t; nht cao; kh nng hp ph cc cht rt
cao, v n c cu trc phc tp, din tch tip xc vi mi trng so vi khi lng rt ln
nn protein c c tnh ny. Cc cht m protein hp ph c th th hi, lng, rn, chng
c lin kt vi phn t protein theo nhiu kiu lin kt, lin kt ny c th bn nu l lin
kt ho hc hoc khng bn nu l lin kt do s hp dn phn t hoc tnh in. im ng
ch l hin tng hp ph ca protein khng hn lon m c tnh c trng r rt m in
hnh l cc phn ng huyt thanh min dch (khng th ch kt hp vi khng nguyn tng
ng). Hin tng trng n ca protein cng c bn cht l hin tng hp ph, cht hp ph
y l nc (protein kh c th hp ph ti 50% khi lng nc so vi bn thn chng) v
c kh nng khuch tn nh sng, khi cho tia sng i qua dung dch protein ta thy c cc
tia khuch tn, hin tng ny gi l hin tng tin an.
7.2. Lng tnh v im ng in: Keo protein l keo trng thi mang in, c th
dng hoc m. in tch trong ht keo l in tch phn ly ca cc gc acid amin d nhm
cacboxyl, nhm amin. in tch ny c th dng hoc m, iu ny ph thuc vo s lng
ca cc nhm -COO
-
v NH
3
+
trong phn t protein.
NH
2
COOH NH
3
+
COO
-

------------------- ------- > --------------------------

COOH COO
-
S phn ly ny cn ph thuc vo pH ca mi trng. Tr s pH mi trng lm cho
phn ly ca cc gc tin ti bng nhau in tch trit tiu th gi tr pH gi l im
ng in, k hiu l pI. Ti im ng in ht keo protein khng bn, v n mt mt yu t
l sc y tnh in. im ng in ca a s protein nm vng di 7, pha acid. V d:
pI ca casein l 4,7; albumin l 4,8; globulin l 5,4.
7.3. Hin tng mt nguyn tnh v sa lng: Protein tn ti n nh trong mi trng
nht nh, khi mi trng thay i (pH v t
0
) lm nh hng ti cu trc bc III, ti in
tch... th mt s tnh cht ca protein thay i nh kh nng xc tc ca cc enzyme b gim
st hoc mt hn, trng hp gi l trng hp mt nguyn tnh.
Khi tc ng ca nhng yu t mi trng khng su sc hoc qu nhanh th phn t
protein c th tr li trng thi ban u (hon nguyn - khi phc li nguyn tnh ca n). Nu
tc ng ca cc yu t mi trng ko di v mnh th protein b bin i tnh cht m ph
bin l cu trc bc III hon ton ri lon, lc mt s thuc tnh ca trng thi keo b mt
nh kh nng c in tch, kh nng thu ho... v cc phn t protein t li vi nhau kt ta
v sa lng.
7.4. Tnh c trng sinh hc: y l s khc nhau ca cc protein v mt cu trc
(trc ht l bc I) v chc nng nh tnh c hiu ca enzyme, hin tng chong do vic
truyn mu, hin tng khng dung ho khi v da hoc cy ghp m... Cc loi phn ng ny
rt tinh vi v phc tp. Tnh c trng sinh hc ny c di truyn cht ch qua acid nucleic.
8. Phn loi protein
Theo tnh ton ca Pauling, trong mt con ngi c khong 10 vn loi protein khc
nhau nn vic phn loi l phc tp. Hin nay ngi ta vn theo ngh ca Hoppezaile v
Dreczen vic phn loi protein l theo 2 lp ln l protein n gin (protein) v protein phc
tp (proteid). Protein n gin l loi protein m thnh phn cu to ch c cc acid amin.
Protein phc tp l loi protein m thnh phn cu to ch yu l cc acid amin, bn cnh
cn c cc nhm ghp khng c bn cht acid amin
8.1. Protein n gin (protein): gm 4 nhm sau:
8.1.1. Albumin v globulin: L nhng protein chc nng ph bin mu v c. Chng
khc nhau v khi lng phn t, albumin khi lng phn t thp hn (2-7 vn dalton),
globulin 1 triu dalton (1dalton = 1,66 x 10
-24
gam).
V chc nng: albumin gn lin vi qu trnh dinh dng, l nguyn liu xy dng m
bo, gi p lc thm thu keo ca mu, mt phn lin kt vi cc cht khc vn chuyn
chng nh vi vitamin, cc acid bo, cholesterin, mt s ion Ca, Mg.... Tiu phn albumin
chim 35-45% protein trong huyt thanh, t l ny phn nh cng trao i cht ca c
th. Albumin c tng hp nhiu gan. T l v hm lng albumin trong mu phn nh
ch dinh dng cao hay thp v chc nng ca gan.
Globulin chim phn ln protein trong huyt thanh, n bao gm nhiu loi nh , , -
globulin, chng c vai tr khc nhau trong c th sng. Hai loi , -globulin c tng hp
ch yu gan, chng gn lin vi qu trnh dinh dng nh albumin. Tiu phn -globulin
lin kt vi glucid v lipid to thnh nhng phc hp glucoproteid v lipoproteid, -globulin
cn lin kt vi Hb khi hng cu b v, bng phng php in di ngi ta tch c -
globulin thnh 2 tiu phn 1 v 2-globulin, trong 2-globulin c cha haptoglobin l
yu t c lin quan ti Hb. Tiu phn -globulin c cha transferin l yu t tham gia vo qu
trnh to mu cho c th. Tiu phn -globulin do t bo lm ba cu B sinh ra, c vai tr c
bit quan trng, l t hp cc khng th, tham gia vo qu trnh min dch ca c th. y l
ch tiu nh gi kh nng chng bnh, kh nng thch nghi ca c th. Ngi ta tch c
5 nhm khng th c c tnh min dch khc nhau l IgG, IgA, IgM, IgD, IgE.
Ch s A/G (Albumin/Globulin) l ch s phn nh tnh trng sc kho, dinh dng ca
con vt.
8.1.2. Histon v protamin: l loi protein kim tnh pI = 8-13. Phn t chng cha
nhiu acid amin kim nh Arg, Lyz, His...c nhiu trong nhn t bo, gn lin vi DNA v
gi vai tr iu ho hot ng ca DNA, vi tnh base cao to thnh poly cation cho
polyanion l DNA bm vo.
8.1.3. protein (proteinoic): l protein ca m lin kt (gn, dy chng, tc, xng...)
c tnh ca chng l tuy c cu to thun tu t cc acid amin nhng chng khng trng
thi keo (khng ho tan trong nc), cu trc thng dng si hoc b. i din ca nhm
ny l:
Colagen: l loi protein c ch yu m lin kt, da, thnh mch qun, t l colagen
tng l cho da nhn nheo khi tui gi. t
0
cao phn t ca chng i sang dng h, dng
gelatin.
Elastin: c nhiu m lin kt gn, dy chng, t l tng khi tui gi, khng tan trong
mi trng nc nng nh colagen.
Keratin: l cht to sng mng, lng, tc, c tnh l c dng si.
Fibroin: l protein ca t tm
8.1.4. Prolamin v Glutelin: l protein c nhiu trong ht ng cc, thnh phn khng
cn bng nhiu acid amin Glu, Pro.
8.2. Protein phc tp (proteid): gm 5 nhm sau:
8.2.1. Glucoproteid: l loi protein phc tp, thnh phn ch yu l cc acid amin,
ngoi ra cn c nhm ghp l cc loi ng hoc dn xut ca ng. Lp ny c vai tr
quan trng trong cu trc mng, gy tnh khng c hiu ca mng nh mng hng cu. i
din ca nhm ny l:
Muxin: c dch nhy (nc bt, bao khp) c tc dng bi trn, gim ma st c hc
bo v c quan, c nhm ghp l mucoitin bao gm glucozamin, acid glucoronic, H
2
SO
4
.
O
CH2OH
NH2
O
COOH
Glucozamin Acid glucoronic
Mucoid: l cht mm ca xng, sn, c nhiu trong lng trng trng.
Acid hyaluronic: l cht xi mng gn cc t bo vi nhau. Enzyme phn gii chng l
hyaluronidase c tnh c hiu theo loi.
8.2.2. Phosphoproteid: l nhng protein phc tp, trong thnh phn c cha gc
phosphoryl, gc ny thng gn vi nhm OH ca Ser, Tre. i in l cht caseinogen trong
sa, ovovidein trong trng, l nhng protein c vai tr dinh dng.
8.2.3. Lipoproteid: l loi protein phc tp, c nhm ghp l lipid, n c c tnh ho
tan trong nc, khng ho tan trong dung mi hu c, thnh phn cn c phospho. Vai tr
ca lp ny l nguyn liu to nn cc loi mng sinh vt. S phn b gia lipid v cc phn
protein trong mng c th khc nhau tng loi mng. Nh c tnh ca lp cht ny lm cho
mng c c tnh thm thu c chn lc i vi cc hp cht, thm ch mng ca ty lp th
thm thu chn lc c vi cc in t v ion. Ngoi vic to cho mng tnh thm thu chn
lc, lp cht ny cn to cho mng tnh cch in, dn in mt chiu...nh mng trong ca ty
lp th l loi mng c tnh dn in mt chiu, ch cho in t chuyn c qua mng, thng
qua tnh cht ny t bo hnh thnh c mt hin tng l th hiu mng (gradien v in
tch), y chnh l c ch ca qu trnh to nng lng cho c th.
8.2.4. Cromoproteid: L loi protein ng o v chnh chng to cho sinh vt c mu
sc. Nguyn tc cu to ngoi phn protein chng cn c nhm ghp, nhm ghp ny c bn
cht khc nhau, chnh nhm ghp ny to cho Cromoproteid c mu sc tng ng nh mu
ca mu, mu en ca mt... cc mu sc c hnh thnh v nhm ghp c cha cc ion
kim loi: cha st cho mu , Mg mu xanh...
Mt s Cromoproteid:
Hemoglobin (Hb) c mu, nhm ghp l Hem
Mioglobin c c, nhm ghp l Hem
Cytocrom c ty lp th, l thnh vin ca chui h hp, nhm ghp l Hem
Rodopxin c vng mc mt, nhm ghp l vitamin A
Hemoglobin (Hb)
L cht mu ca hng cu, hm lng trong mu c th kho mnh t 8-12g%, n
l cht vn chuyn kh gia phi v m bo.
V cu to: Hemoglobin gm protein l globin chim 94% + nhm ghp l hem chim
4,6%, khi lng phn t 67.000 dalton. Hb c 4 tiu phn:
2 tiu phn k hiu l mi tiu phn c 141 acid amin
2 tiu phn k hiu l mi tiu phn c 146 acid amin
Tng s khong 600 gc acid amin Mi tiu phn c mt nhm hem, 4 tiu phn ny
lin kt vi nhau bng cu trc bc IV, c b cc trong khng gian thnh hnh t din u,
ng knh 50A
0
. Trong mt hng cu c khong 280 triu phn t Hb.
Phn globin ca cc tiu phn v c s khc nhau v cu trc bc I v III. S khc
nhau gia cc loi Hb trong mt c th cng nh gia cc loi l do s khc nhau ca globin
m ch yu tiu phn . S khc nhau ny to kh nng cho Hb hp thu c nhiu hay
t 0
2
trong phn chc nng ca mnh. bo thai chui c thay bng chui to thnh
HbF, ng vt ln dn th chui s thay dn cho chui . ng vt c hng cu hnh li
lim tc l HbS y l do tnh n hi ca hng cu b mt nn khi chng i qua cc viti
huyt qun c ng knh nh hn ng knh hng cu, chng khng tr li dng cu c
m gi nguyn trng thi mo m , t nh hng ti chc nng ca hng cu, gy nn
cht sm. Nguyn nhn su xa l do chui trong tng s 146 acid amin c acid amin th 6
b thay i, bnh thng l acid amin Glu (tnh acid), ngi b bnh l acid amin Val (trung
tnh) khc nhau mt ng l a nc, mt ng l k nc dn n tnh n hi b mt.
Nhm Hem: cu to ca nhm hem cc loi mu u ging nhau, cu to gm 4 vng
pirol ni vi nhau bi 4 dy ni metyn (= CH - ), c 2 gc vinyl (- CH = CH
2
), 4 gc metyl (-
CH
3
), 2 gc acid propionic (- CH
2
- CH
2
- COOH), to thnh protoporfirin. Hem l hp cht
st ho tr 2 vi protoporfirin. Nhm hem ni vi globin bi cc dy ni tnh in, cc dy ni
ny khng bn nn hem d b tch ra (hnh 1.26).
Vai tr ca Hemoglobin: Vai tr chnh ca hemoglobin l chuyn kh gia phi vi
m bo:
Vn chuyn 0
2
: 0
2
gn vi hem bi cc dy ni ph (khng thay i ho tr). S lin kt
ny ph thuc vo p sut ring ca 0
2
. 0
2
phi c p sut ring l 158mmHg, Hb tip thu
0
2
; m bo p sut ca 0
2
l 40mmHg, 0
2
c nh ra dng vo qu trnh ho sinh hc.

Vn chuyn C0
2
: m bo phn p C0
2
cao n gn vi Hb qua cc nhm amin cht ca
hemoglobin thnh dng Cac-Hb:
R - NH
2
+ C0
2
---------> R NH. C00H.
S vn chuyn C0
2
theo cch ny chim khong 20%, cn 80% C0
2
lin kt vi kim
ca huyt tng v hng cu thnh nhng bicabonat nh NaHC0
3
, KHC0
3
... ti phi n
chuyn sang dng acid cacbonic v thi ra ngoi:
NaHC0
3
+ H
+
----------> Na
+
+ H
2
0 + C0
2
Ngoi lin kt vi 0
2
v C0
2,
hemoglobin cn lin kt vi cc cht khc:
Hemoglobin d b o xy ho bi cc cht o xy ho nh K
3
[Fe (CN)
6
], HN0
3
... lc ny st
chuyn sang ho tr 3 to thnh Met - Hb (Fe
+3
- OH). Nu thi gian th nhm OH t phn
ly v st 3 s chuyn v st 2.
Hemoglobin c i lc rt mnh vi C0, ch cn nng ca C0 trong khng kh ln
10% th 95% Hb s lin kt vi C0 v c th s b ngt, lc ny st cng chuyn sang ho tr
3.
Vi HCN, KCN, Hb chuyn sang dng xyanmet Hb (Fe
+3
- CN), c th cng lc ny
cng b nhim c do ngt.
Nhm hem cn c trong Mioglobin ca c, Mioglobin c 2 tiu phn, l cht d tr O
2

Hnh 1.26. S cu trc ca Hem
V st: ton b c th ngi c 5 lt mu, tng s st l 5g. Qu trnh hp thu st kh
phc tp nn khi hng cu v, st c gi li.
8.2.5. Nucleoproteid: y l loi protein phc tp, thnh phn ca n gm c protein l
cc protein kim tnh nh histon v protamin v nhm ghp l acid nucleic.
Histon v protamin l nhng protein ca nhn t bo, n thng gn vi DNA ca nhn.
y l nhng protein kim tnh, cu to ca n thng l cc acid amin kim nh Lyzin,
Prolin, Histidin... cu trc phn t ca chng to nn mt polication cho DNA l mt
polianion bm vo.
Yu cu sinh vin cn nm c:
Khi nim cu to v chc nng ca protein ni chung, ca Albumin v
Globulin, Glucoproteit, Lipoproteit, Hemoglobin
YU CU CN NM
CHNG I: PROTEIN CU TRC V CHC NNG
Khi nim cu to v chc nng ca protein ni chung, ca Albumin v
Globulin, Glucoproteit, Lipoproteit, Hemoglobin
Cu 1: Khi nim v chc nng ca protein
Cu 2: Cu trc bc I ca protit? ngha sinh hc ca cu trc ny?
Cu 3: Th no l axt amin khng thay th? Vit cng thc ca nhng axt amin ?
Cu 4: Cu trc bc III ca protit? Mi lin quan gia cu trc ny vi hot tnh sinh
hc ca protit?
Cu 5: Cho bit c im, vai tr ca albumin v globulin
Cu 6: c im cu to v vai tr sinh hc ca Hemoglobin (Hb)?
Cu 7: Cu trc, chc nng ca - Globulin ?
CHNG II
ACID NUCLEIC V C CH DI TRUYN T BO
1. Khi nim:
V mt sinh hc: Acid nucleic l cht mang cc c tnh di truyn ca sinh vt, l bn
mt m di truyn cha tt c cc thng tin di truyn. Ngoi ra cn c loi acid nucleic (RNA)
tham gia vo qu trnh truyn t bn mt m sang dng protein.
V mt ho hc: Acid nucleic l nhng polyme t nhin c cu to t cc monome
l cc nucleotide.
2. Cu trc ca Acid nucleic
Acid nucleic chia lm 2 loi l: DNA v RNA.
DNA: Desoxyribonucleic acid
RNA: Ribonucleic acid
Chng l cc polyme c cu to t cc monome nucleotide.
2.1. Nucleotide
Nucleotide c 3 thnh phn: Base nit, ng 5 carbon, v acid phosphoric. Ba thnh
phn ny nhn c khi thu phn nucleotide.
2.1.1. Base nit.
Hai loi Base nit c tm thy trong nucleotide l dn xut ca pyrimidine v purine d
vng thm. Purine l dn xut ca vng pyrimidine v imidazole.
Mononucleotide Pyrimidine Purine
Cch nh s ca Chu u Cch nh s ca M

Ba se Pyrimidine: Base pyrimidine c tm thy trong nucleotide l:
Cytosine vit tt l C: v tr 6 c nhm amin (NH
2
), v tr 2 c nhm OH.
Uracil vit tt l U: v tr 6 v 2 c nhm OH, U ch c trong RNA.
Thymine vit tt l T: v tr 6 v 2 c nhm OH, v tr 5 c nhm metyl -CH
3
, T ch c
trong DNA
Cc pyrimidine chnh
Cytosine Uracil Thymine
(2-0ci-4-aminpyrimidine) (2,4-diocpyrimidine) (5-methyl-2,4-oxyprimidine)
Phosphate
Base purine
haypyrimindin
Base Purine: Hai base Purine chnh tm thy trong Nucleotide l Adenine v Guanine,
vit tt l A v G.
Mt s base purine him nh: 2-methylAdenine v 1-methyl-Guanine. Ngoi ra, mt s
t base pyrimidine him cng c tm thy l 5-methylcytosine, 5-hydroxymethylcytosine.
Cc tnh cht ca base purine v pyrimidine rt ging nhau. Chng t ho trong nc v
tn ti dng h bin: ngha l c kh nng bin i gia dng lactim (dng enol) v dng
latam (dng ketone).
Tt c cc base purine v pyrimidine ca acid nucleic hp th rt mnh nh sng t
ngoi trong vng bc sng t 260 n 280nm. Kh nng hp th cc i bc sng 260
nm. Tnh cht ny c ngha ln nh tnh v nh lng khng ch cc base t do m c
cc nucleoside, nucleotide v phn t acid nucleic nguyn vn.
Cc base purine v pyrimidine rt d phn tch v nhn bit bng phng php sc k
giy hoc sc k lp mng
2.1.2. ng Pentose.
Cc Purine chnh
Adeninee Guaninee
(6-aminpurine) (2-amin-6-oxypurine)
Trong acid nucleic c cha ng 5 carbon dng -D-furanose. Chng c chia
lm 2 loi l ribose v desoxyribose. Acid nucleic cha desoxyribose gi l desoxyribonucleic
acid (DNA). phn bit cc bon ca ng ngi ta thm du phy cc v tr ca n, v d
3, 5 l ch v tr C s 3, s 5 ca ng.
ng ribose ng desoxyribose
2.1.3. Acid phosphoric: trong nucleotide n gn vi ng hoc v tr C
5
hoc v tr
C
3
v c cch ghi chp tng ng l 5
/
- phosphate hoc 3
/
- phosphate.
Trong cc nucleotide t do H
3
P0
4
hay gi l gc phosphoryl bao gi cng gn v tr C
5
vi s lng c th t 1,2,3 gc, tng ng c cc hp cht l mono, di, tri phosphate.
Cch c: Base purin c ui l ozin: adenine c l adenozin; guanine c l
guanozin, v d: adenine + pentose + H
3
P0
4
c l Adenozin mono phosphate.
Base pirimidin c ui l idin: Cytosine c l Cythydine; Uracil c l Uridine v
Thymine c l thymidin, v d: thymine + pentose + H
3
P0
4
c l Timidin mono phosphate.
Cch vit: V d1: Adenozin mono phosphate(AMP): ng gn vi base qua v tr N
s 9 ca base, phosphate gn vi ng qua v tr C s 5 ca ng. Khi tn ti dng mono
phosphat th gi l acid adenylic, nu gn vi 2 gc phosphate th gi l Adenozin di
phosphate (ADP) nu l 3 gc phosphate th gi l Adenozin tri phosphate (ATP).
V d 2: Uridine mono phosphate: ng gn vi v tr 3 ca base, phosphate gn vi v
tr 5 ca ng. Tng t ta cng c cc hp cht UMP, UDP. UTP.
N
N
N
N
NH
2
O
H OH
H H
H H
O
H OH
H H
H H
NH
O
O N
H
3
C
AMP
TMP
O P -O
O-
O
CH2
O P -O
O-
O
CH2
Cc nucleotide khi trc n c ch D l ch ng cu to ca n l desoxyribose.
2.1.4. Nucleoside.
Khi nucleotide b thu phn lm mt gc phosphate to thnh nucleoside. Lin kt gia
cc nucleoside l N-glycoside lin kt gia cc base purine v pyrimidine, trong nguyn t
carbon 1 ca pentose lin kt vi nguyn t N
3
ca pyrimidine hay nguyn t N
9
ca purine.
Ribonucleoside c thnh phn ng l D-ribose, v 2-desoxyribonucleoside, c 2-desoxy-
D-ribose. Tn ca 4 nucleoside chnh l adenoseine, guanoseine Cythydine, Uridine v 4
desoxyribonucleoside chnh l 2-desoxyadenoseine, 2-desoxyguanoseine, 2-
desoxycididine, 2-desoxythymidine.
Cc nucleotide ho tan rt nhiu trong nc, hn c cc gc base ca chng. Chng
cng c phn tch d dng bi sc k lp mng hay sc k giy.
Nucleoside d dng b thu phn khi un nng trong acid. Sn phm ca s thu phn l
cc base ni t v cc pentose t do, cc nucleoside pyrimidine bn hn cc nucleoside purine.
Cc nucleoside cn b thu phn bi cc nucleoseidase chuyn ho.
Hai nucleoseine
Adenoseine 2-Desoxyadenosein(q- -D-
ribofuranoseilAdenine (q- -D-2
-desoxy-D-ribofuranoseilAdenine)
2.1.5. Nucleotide.
Nucleotide l ester ca acid phosphoric v nucleoside. Acid phosphoric lin kt vi
nhm OH t do ca pentose. Nucleotide t do c vai tr rt quan trng trong tt c cc t bo.
Chng cng c to thnh khi thu phn nh acid nucleic, c bit l bi Enzyme nuclease.
Nucleotide c 2-desoxy-D-ribose l desoxyribonucleotide, nu c D-ribose c gi l
ribonucleotide. Trong nucleoside c 2 hoc 3 nhm OH t do, nhm phosphate c th lin kt
vi nhng v tr trn pentose. Trong trng hp desoxyribonucleotide, acid phosphoric c
th ester ho v tr 3 v 5. C hai loi 3- v 5-desoxyribonucleotide u thy cc c th
sinh vt cn ribonucleotide th nhm phosphate c th v tr 2, 3 v 5. Tt c 3 loi
ribonucleotide l sn phm ca RNA, ph thuc vo iu kin thu phn, monophosphate
vng ca Adenoseine cng c tn ti. Tuy nhin, nucleotide dng t do trong t bo c
nhm phosphate v tr 5 chim u th. V vy, cc phn ng Enzyme khi tng hp hay
phn gii acid nucleic trong t bo th nucleoside-5-phosphate l cht trung gian. Hnh 2.1 l
cu trc c bn v cch gi tn ca cc ribonucleoside 5-monophosphate chnh (cn gi l
5-ribonucleotide) v desoxyribonucleoside-5-monophosphate (cn gi l 5-desoxyribo
nucleotide) thng cn c tn acid adenilic, acid guanilic, acid uridilic...)
Cu trc chung Cu trc chung

Adenine ribonucleoside
Monophosphate
Acid adenoseine 5
-phosphateric Acid adenoseine 3
-phosphateric Acid adenoseine 2
-phosphateric
Acid adenoseine 3
, 5
-phosphateric
(Acid adenilic; acid 5
-adenilic) (Acid acid 3
-adenilic) (Acid 2
-adenilic) (Acid adenilic chu trnh)

Hnh 2.1.Cc ribonucleotide v desoxyribonucleotide chnh
Ribonucleoside 2' - desoxyribonucleoside
5' - monophosphate 5' - monophosphate

Bng 2.1. Tn gi v vit tt ca mono nucleotide
Tn Tn
Acid adenoseine 5-phosphoric
(Aciddenilic; AMP)
Acid guanoseine 5-phosphoric
(Acid guanilic; GMP)
Acid cytidin 5-monophosphate
(Acid cytidilic; CMP)
Acid uridine 5-phosphoric
(Acid uridilic; UMP)
Acid desoxyadenoseine 5-phosphoric
(Acid desoxyadenilic; dAMP)
Acid desoxyguanoseine 5-phosphoric
(Acid desoxyguanilic; dGMP)
Acid desoxycytidin 5-phosphoric
(Acid desoxycytidilic; dCMP)
Aciddesoxythymidin 5-phosphoric
(Acid desoxythymidilic; dTMP)
Cc mono nucleotide c cc base purine v pyrimidine nn hp th nh sng mnh
bc sng 260nm. Chng d dng c phn tch bi cc phng php sc k lp mng, sc
k giy, sc k trao i ion.
Nhm 5-phosphate ca cc nucleotide d dng b thu phn bi acid. Ngoi ra enzyme
5-nucleotidase cng thu phn c nhm phosphate v tr 5, nhng khng phn gii lin
lt N-glycoside.
2.1.5. Cc nucleoside 5-diphosphate (NDP) v 5-triphosphate (NTP):
Cc hp cht ca ribonucleoside v 2-desoxyribonucleoside nh 5-diphosphate v 5-
triphosphate cng c tm thy trong t bo. Cu to chung v vit tt c gii thiu hnh
2.2.
Nhm phosphate ca hp cht c ghi bng k hiu . , , Tt c NTP v NDP u
c trong t bo, c th tch chit bng acid.

Vit tt ca Ribonucleoside
5-phosphate
Base Mono -Di -Tri
Adenine
Guanine
Cytosine
Uracil
AMP
GMP
CMP
UMP
ADP
GDP
CDP
UDP
ATP
GTP
CTP
UTP
Vit tt ca desoxyribonucleoside
5-phosphate
Base
Adenine
Guanine
Cytosine
Thymine

dAMP
dGMP
dCMP
dTMP
-Di
dADP
dGDP
dCDP
dTDP
-Tri
dATP
dGTP
dCTP
dTTP
Hnh 2.2. Cu to chung ca nucleoside
5-mono-, 5-di-, v 5-triphosphate
(NMP, NDP v NTP) v cc ch vit tt.
Trong desoxyribonucleotide, pentose l
2-desoxy-D-ribose.
Nucleoside 5
-monophophate (NMP)
Nucleoside 5
-diphophate (NDP)
Nucleoside 5
-triphophate (NMP)
NTP c nhiu chc nng quan trng, ATP l cht mang nng lng ho hc c bn
trong t bo, cung cp vn chuyn cc nhm phosphate cao nng n cc qu trnh i hi
nng lng. Dng ADP v AMP c phosphoryl ho thnh ATP trong qu trnh h hp.
ATP-ADP l cp c bn hoc l ng chnh vn chuyn phosphate trong t bo. Ngoi ra
cc ngun NTP khc cng cung cp nng lng do lin kt phospho trong cc phn ng sinh
tng hp.
Chc nng chnh th 2 ca NTP v NDP l cc cht mang c bit nh Uridine
diphosphate (UDP)- mang gc ng trong tng hp polysacchacaride. Th d Uridine
diphosphate glucose nhng gc glucose trong sinh tng hp ca glycogen. Tng t,
Cytidine diphosphate choline chuyn Choline trong sinh tng hp phospho glicerol choline.
Uridine diphosphate Glucose Cytidine diphosphate choline
(UDPG)
Chc nng chnh th 3 ca NTP l nhng tin cht giu nng lng ca cc n v nucleotide
trong tng hp Enzyme ca cc DNA v RNA.
Trong cc phn ng ny cc NTP mt nhm pyrophosphate, tr thnh gc nucleoside
monophosphate ca acid nucleic.
Ngoi ra NTP cn c th chyn ho thnh nucleotide vng nh 3
/,
5
/
- AMP vng; 3
/,
5
/
- GMP
vng, chng c vai tr trung gian trong hot ng ca hormone vi t bo, chng l cc thng tin
ni bo di tc dng ca h thng enzyme adenylacyclase hay guanylatcyclase. Mi s bin i
ca c th p ng vi ngoi cnh cng nh vi qu trnh pht trin c th u thng qua vic
tc ng n t bo m kt thc l lm thay i s hot ng ca cc enzyme trong t bo, s tc
ng ny l thng qua nucleotide vng.
3',5'-AMP vng 3',5'-GMP vng
2.1.6. Cc mononucleotide khc.
C nhiu mononucleotide quan trng khc nh nicotinamide mononucleotide v
coEnzyme A, cc base nit ca chng c lin kt -N-glycoside v tr 1 ca D-ribose.
(Hnh 2.3). Nicotinamide mononucleotide v flavinmononucleotide c nicotinamide v 7,8-
dimethylizoallocaseine l cc base nit. Acid nicotinic l vitamin cn thit trong dinh dng
ca ngi v nhiu ng vt. S thiu ht n l nguyn nhn ca bnh Pellaga gy cht ngi
v bnh li en ca ch.

Acidpanto
tenic
-ercatoetilamine
Nicotinamide ononucleotide (FMN)
`Nicotinamide
CoenzymeA
`Flavin mononucleotidee (FMN)
(riboflavin phosphate)
7-8-Dimethylizoalloasein
3
Phosphoadenose
ine diphosphate
(3
P ADP)
Acid
pantotenic
- ecaptoethylamine
Acid nicotinic
Hinh 2.3. CoEnzyme mononucleotide. Chng u c vitamin tham gia
FMN c cha alcohol D-ribotol, ng 5 carbon. Khc vi D-ribose n l coEnzyme oxy ho kh
quan trng tham gia vo qu trnh h hp. Vng izoallocasein b oxy ho kh thun nghch. FMN
cng l tin cht trong tng hp ca flavin Adenine dinucleotide (FAD).
CoEnzyme A c Adenine lin kt -glucoside vi v tr 1 ca D-ribose. v tr 5 ca
D-ribose c nhm acid pyrophosphoric, n c ester ho vi hp cht peptide.
Panthotenyl -aminethantiol 8 -mercaptoethylamine. Acid panthotinic l mt vitamin
ca nhm B, n cn thit trong dinh dng ca tt c ng vt c xng sng, chc nng ca
coEnzyme A l mang nhm acetyl v acyl ca acid bo, chng c ester ho thnh nhm
thiol.
2.2. Dinucleotide.
Dinucleotide gm c 2 n v mononucleotide
c ni vi nhau bi cu acid phosphoric (hnh 2.4).
Phn ln dinucleotide l sn phm ca s thu phn
acid nucleic bi Enzyme. Nh vy trong dinucleotide
cu lin kt l phosphodiester gia v tr 5 ca D-
ribose ca 1 nucleotide vi v tr 3- ca 1 nucleotide
khc. C mt s dinucleotide c bit trong nhm
phosphate ging vi lin kt 3, 5- phosphodiester,
chng khng nhn c t acid nucleic m tm thy
dng t do trong t bo. Th d 3 coEnzyme oxy ho-
kh c hiu bit y nht l nicotinamide
Adenine dinucleotide (NAD), nicotinamide Adenine
dinucleotide 2-phosphate (NADP) v Flavin Adenine
dinucleotide (FAD). Mi mt coEnzyme c cha
adenoseine 5-monophosphate; NAD v NADP lun
lun c nicotinamide mononucleotidee (Hnh 2.5).

Trong c 3 Enzyme, 2 n v mononucleotide c ni vi nhau bi lin kt anhydride
gia nhm phosphate ca chng to thnh cu 3,5-pyrophosphate. NADP nhn c t
NAD, n c ester ho bi mt phn t acid phosphoric khc n v tr 2 ca Adenine
mononucleotide. Chnh NAD v NADP l coEnzyme trong h Enzyme phn ng oxy ho
kh.
FAD gn 1 phn t ca Adenine ribonucleotide v 1 ca flavin mono nucleotide ni vi
nhau bi lin kt anhydride gia cc nhm 5-phosphate ca chng. Chu trnh izoallocasein
ca FMN v FAD oxy ho kh thun nghch.
Hnh 2.4. Cu acid phosphoric (hay lin
kt 3,5 phosphodieste) trong
dinucleotide
2.3. Cu trc bc I ca acid nucleic: y l cch lin kt gia cc nucleotide li vi
nhau thng qua lin kt phospho este to nn chui nucleotide. Lin kt phospho este l
lin kt c hnh thnh nh s lin kt gia acid phosphoric ca nucleotide ny vi cc bon
s 3 ca pentose nucleotide bn cnh. Nh vy phn base c t do, ng v phosphate
to thnh dy ni. V d ta c on nucleotide: A-X-U.
Hnh 2.5
Cc coEnzyme dinucleotide
Flavin Adenine dinucleotide (FAD)
Nicotinamide Adenine dinucleotide (NAD) cn c
gi l diphosphopyrimidine nucleotide (DPN).
Nicotinamide Adenine dinucleotide phosphate
(NADP) cng c gi l triphosphopyrimidine
nucleotide (TPN), n c 3 nhm phosphate.
Trong NADP nhn OH ny
c ester ho vi phosphate
Nicotinamid
e
N
N
N
N
NH
2
O
H O
H H
H H
H
2
C
N
NH
2
O N
O
H O
H H
H H
P O
O-
O
OH
CH
2
P O O
OH
NH
O
O N
O
OH OH
H H
H H
H
2
C P O O
OH
c im ca chui:
u chui c mt gc phosphate t do gi l u 5
/
- P. Cui chui c mt gc OH C
s 3 ca ng trng thi t do gi l ui 3
/
- OH.
Trong chui nucleotide c c im quan trng sau:
Th t sp xp trc sau ca cc nucleotide (hay ni khc i l ca cc base) l nn
tng ca hin tng di truyn. N to nn tnh c trng sinh hc ca acid nucleic, t
quyt nh cu trc di truyn bc I ca protein. V ch c 5 loi base, nu xt tng loi acid
nucleic th ch c 4, m acid nucleic l m di truyn cho cu trc bc I ca protein, tc l phi
m c cho 20 loi acid amin, m kh nng khc nhau li ch c 4, vy th mu thun.
gii quyt mu thun ny nu t hp 2 nucleotide cho 1 m th ta c 4
2
= 16 kh nng, nh
vy vn cha c. Nu t hp 3 nucleotide cho 1 m ta c 4
3
= 64 kh nng. kin ny
c Crik xut v c Nirenberg v Mathei (ngi M) thc nghim (1964) nh s tng
hp c chui poli U, t khun mu ny v cc nguyn liu cn c tng hp nn mt
chui peptide vi ton b l Phe-Phe-Phe... v bng phng php th ngi ta tm c
ton b cc m cho 20 acid amin. V d AUG m cho Met, UUA m cho Leu...

Bng 2.2. Bng m sinh tng hp protein (bng m di truyn)
U C A G
U
UUU Phe
UUC Phe
UUA Leu
UUG Leu
UCU Ser
UCC Ser
UCA Ser
UCG Ser
UAU Tyr
UAC Tyr
UAA
UAG
UGU Cys
UGC Cys
UGA
UGG Try
U
C
A
G
C
CUU Leu
CUC Leu
CUA Leu
CUG Leu
CCU Pro
CCC Pro
CCA Pro
CCG Pro
CAU His
CAC His
CAA Glu
CAG Glu
CGU Arg
CGC Arg
CGA Arg
CGG Arg
U
C
A
G
A
AUU ILeu
AUC ILeu
AUA ILeu
AUG Met
ACU Tre
ACC Tre
ACA Tre
ACG Tre
AAU Asp
AAC Asp
AAA Lys
AAG Lys
AGU Ser
ACC Ser
AGA Arg
AGG Arg
U
C
A
G
G
GUU Val
GUC Val
GUA Val
GUG Val
GCU Ala
GCC Ala
GCA Ala
GCG Ala
GAU Asp
GAC Asp
GAA Glu
GAG Glu
GGU Gly
GGC Gly
GGA Gly
GGG Gly
U
C
A
G
Th t cc base trong cu trc bc I quyt nh tnh c trng sinh hc ca acid nucleic
ch yu cng tnh theo b 3 ny, hay ni khc i m di truyn c ghi di dng nhng b 3
nucleotide. Nhng b 3 ny gi l codon (code: m). Mi codon ng vi mt acid amin. Cc
codon nm trn chui nucleotide trong phn t acid nucleic theo trnh t lin tc khng c
ngt qung hay gi l bn m khng c du phy. Khi c s t bin th m di truyn thay i
gy nn s bin d. S t bin ny c th mt nucleotide mt i hoc thm vo chui lm cho
m thay i dn n s thay i acid amin trong chui peptide.
ngha quyt nh trong 1 m l 2 base u, base cui c th thay i, nn 1 acid amin
c th c nhiu m ( 64 m) v d AUX: ILue th AU l quyt nh, cn X c th bin ng,
xem bng m (bng 2.2).
V s lng nucleotide trong chui kh bin ng t 30 n hng triu nucleotid (bn
gen ngi l 30-40.000) n quyt nh di v khi lng phn t ca acid nucleic.
2.4. Cu trc bc II ca acid nucleic: L cch gn cc chui nucleotide vi nhau thnh
nhng dng xon kp kiu xon thng. Xon kp c th xut hin gia 2 chui ring bit nh
DNA, hoc trong phm vi mt chui, nu nh dc theo chui c cc base b sung nhau to
c lin kt hydro.
Cu trc bc II ca DNA:
DNA u tin c tch chit t bch
cu v tinh dch c v c nghin cu k bi
Friedrich Miescher ngi c t 1869. C rt
nhiu nghin cu v acid nucleic t khi pht
hin ra n, song v cu trc ca DNA th mi
c cp n t 1950.
Lut Chargaff: Trong phn t DNA c
Cytosine(C) v Thymine (T), khng c Uracil
(U)- ng pentose l desoxypentose. Khi
nghin cu hm lng cc nucleotide trong
DNA Chargaff (1953) nhn thy cc base
nit c t l xc inh. Tnh quy lut ny gi l
lut Chargaff;
Tng s gc A = tng s gc T ( A= T)
Tng s gc G = tng s gc C
( G= C)
C th biu din quy lut nh sau:
T c th thy: Tng cc base purine
(A+G)= tng cc base pyrimidine (T+C)
Tng cc base c nhm 6-amin = tng cc
base c nhm 6-ketone. Ngha l:
Hnh 2.6. Cu trc ca DNA v RNA
DNA RNA
u 5'-P u 5'-P
u 3
-OH u 3
-OH
Tuy nhin, ngoi nhng base chnh, trong mt s DNA cn c mt lng nh base nit
methyl ho, chng c tm thy trong DNA ca virus.
Nhng kin ca Watson- Crik: Lut Chargaff cho thy trong DNA, s Thymine bng
s Adenine, Guanine bng Cytosine. James Waston v Francis Crick cho rng Adenine bt
cp vi Thymine, Guanine vi Cytosine. Cc lin kt hydro c sinh ra gia cc cp base
. Kt hp vi nh nhiu x rnghen tinh th DNA do Rosalin Franklin v Marince Wilkin
nghin cu nm 1953, Watson v Crick a ra m hnh cu trc xon kp ca phn t
DNA (Hnh 2.7) v nm 1962, hai ng nhn c gii thng Nobel. kin ca Watson-
Crik thnh nhng nguyn tc sau:
1. Cu trc ca DNA l 2 chui xon li kiu xon thng, hai chui xon ny i ngc
chiu nhau lm cho n cun cht vi nhau hn, t b nh hng ca mi trng. Mt chui i
t 5
/
- P n 3
/
- OH v mt chui i t 3
/
- OH n 5
/
- P.
Hnh 2.7. M hnh lin kt hydro trong cc cp base b sung ca Watson v Crick.
Ngy nay ngi ta pht hin c mt s kiu xon kp ca DNA khc vi m hnh ca Watson Crick (Hnh 2.9)
2. Hai chui c cng c bi cc base hng vo bn trong ca chui v gia cc base
hai bn c lin kt hydro xut hin n nh cu trc. Lin kt hydro ny xut hin gia N
ca amin vi oxy ca ceto ca 2 base i din v gia N
1
ca base ny vi N
1
ca base i
din. tho mn iu kin lin kt hydro ny th DNA ch c cc cp kim sau y:
Adenine ca chui ny lin kt vi Thymine ca chui kia v
Guanine ca chui ny lin kt vi Cytosine ca chui kia.
c tnh Kiu xon
B A Z
-Chiu xon
-S gc nucleotide 1 chu
trnh xon
-ng knh xon(A )
-Khong cch 2
Nucleotide k nhau(A )
-Chiu di 1 chu trnh
xon (A )
Phi
10
20
3.4
34
Phi
10.9
10.9
2.9
32
Tri
12
18
3.5-4.1
45
Hnh 2.8 .Kiu xon kp ca DNA
M hnh xon kp phn t DNA ca Wastson v
Crick
Cc cp base ca 2 chui
polynudeotide lin kt vi nhau
Hnh 2.9. So snh cc dng A, B v Z ca
DNA. C 24 cp base trong 1 cu trc.
A B Z
3. Do cu trc ca chui xon kp c ng knh dc theo phn t l u nhau v bng
khong 20 A
0
do cc base ni vi nhau mt bn l purin th bn kia phi l pirimidin.
Cc i kim ni vi nhau theo nguyn tc 2 v 3 gi l nguyn tc b sung gc kim.
Nguyn tc ny l nguyn tc c bn ca sinh hc phn t n l nn tng cu trc ca DNA
v l nn tng cho bt k mt chui kp no trong acid nucleic ni chung (nh cc on xon
kp trong RNA), nguyn tc ny chi phi cc qu trnh sinh hc ch cht nht nh qu trnh
nhn i DNA, qu trnh sao chp v phin dch m di truyn.
Ngoi lin kt hydro hai chui cn c cng c bng cc yu t khc l s tng
tc gia cc lp base nm chng ln nhau nh nhng chng ng xu (to nn lc Valderval).
Theo Watson v Crick, hai chui polynucleotide ca phn t DNA to thnh cu trc
xon, cun xung quanh mt trc. Mi chu k xon c 10 nucleotide. Mi bc xon l 34A,
ng knh 20A. B khung ca n l mt chui phosphate-ng. Khong cch bn trong
theo mt kch thc nht nh. Trong khong cch ny phn b cc base purine v pyrimidine
khi bt cp th gia Adenine v Thymine c 2 lin kt hydro, gia Guanine v Cytosine c
3 lin kt hydro (hnh 2.8).
Khc vi kiu A v B, kiu Z cc nguyn t P sp xp trn phn t theo dng dch
dc. Ngoi ra ngi ta cng gi thit rng kiu B thch hp cho qu trnh t sao chp DNA,
cn kiu A thch hp cho qu trnh sao chp. Ngoi cc phn t DNA xon kp ph bin t
bo sinh vt, mt s virus c cu to DNA si n (hnh 2.9).
Dng t nhin ca phn t DNA: Si DNA c th tn ti cc dng sau:
Dng xon kp si thng c cc u 3 v 5 t do. Dng ny gp t bo nhn chun
(Eucaryote), DNA thc khun th T
7
.
Dng xon kp kn c th c cc kiu sau:
Dng xon kp 1 si nh DNA thc khun th x174(Virus gy nhim Ecoli).
Dng xon kp (2si): DNA ca t bo nhn x. DNA ca virus ng vt nh polyoma,
SV40, plasmid, DNA ca ty th, lc lp. C th l DNA xon kp kn ng ho tr
(Covalently closed cyclic duplec DNA). Khng c u 3 v 5 t do, hoc DNA xon kp
m (open cyclic DNA), 1 trong hai si b t 1 lin kt phosphodisete to thnh u 3 v 5
t do (hnh 2.10). Dng xon kp kn c th vn xon li thnh dng siu xon.
Hnh 2.10. Cc dng cu trc ca phn t DNA (1) dng m, (2) dng xon m,
(3) dng siu xon
(1) (2) (3)
Kch thc ca phn t DNA: Trong cc t bo nhn x (procaryote) c nhim sc th
n, thc cht DNA l nhng i phn t c khi lng 2 x10
9
.
vi khun, phn t DNA n chim khong 1% khi lng ca t bo, to thnh vng
nhn, n thng gn vi np mng t bo gi l mezosome. Trong vi khun khng c Protein
lin kt vi DNA.
Trong nguyn sinh cht ca vi khun, thnh thong cn tm thy phn t DNA ngoi
nhim sc th, chng nh hn nhim sc th, c gi l plasmid hay epicom, c lin quan
n s di truyn ca DNA nhim sc th.
Vi cc t bo nhn chun lng bi, gn nh tt c DNA trong nhn t bo, n c
lin kt vi protein kim l histon, nm ri rc nhim sc th. Trong cc t bo nhn chun
cn c 1 lng nh DNA nguyn sinh cht, thng c gi l DNA th yu, chng c hp
cht base v khi lng phn t khc vi DNA nhn, nh DNA trong ty th chim khong
0,1-0,2% DNA ca ton t bo. Mt s lp th ca cc t bo thc vt, c bit l cc lc lp
cng c DNA ring bit.
Bng 2.3: Kch thc DNA mt s vi sinh vt.
C th S cp nucleotide (Kb)
Chiu di( m )
Virus:
- SV 40
-Lamda
Vi khun:
-Mycoplasma
-E.Coli
Sinh vt c nhn:
- Nm men
- Ngi
5.1
48.6
760
4000
13-500
2-900 000
1.7
17,0
260,0
1 360,0
56 000,0
990 000,0
2.5. Cu trc bc III v siu cu trc:
Trong nhn t bo DNA cc t nhim sc, 1 nhim sc th l 1 chui kp nucleic, do
phi c s xon li ca nucleic cho gn tc l nhim sc th l xon nhiu tng ca chui
xon kp. Trong nhim sc th c histon (protein c trng cho nhn) c im ca histon l
kim tnh, c th coi histon l mt poli cation, bn thn acid nucleic l 1 polianion lm cho
histon gn cht vi acid nucleic, c th v histon nh li cun ch v DNA nh si ch qun
vo to thnh nucleoxom.
3. Phn loi acid nucleic
Da vo chc nng v cu to ngi ta chia acid nucleic thnh 2 lp ln: DNA v
RNA, chng khc nhau bi mt s im sau:
3.1. Thnh phn cu to: DNA c cha T v ng desoxyribose, RNA cha U v
ng ribose. Tuy nhin c mt s t DNA c cha U v RNA c cha T.
3.2. V phn b: DNA trong t bo phn b ch yu trong nhn, trong nhn TB n
dng m tc l chui xon kp c hai u. Mt phn rt nh c ty lp th, y DNA
dng xon kp kn to thnh vng nhn ging nh VSV. VSV n bo ngoi chui xon
kp DNA chnh cn c cc chui xon kp nh c khi lng phn t khong 1 triu dalton,
gi l th plasmid y l yu t khng thuc, n c th di truyn ring v c th chui sang t
bo khc k c t bo ng vt ri m vng nhn gn vo DNA ca t bo lm tng gennom,
khi n c tn l epicom, t epicom li c th tch ra thnh plasmid. Gn y gi ta
pht hin ra mt chng loi Retravirus (virus hi qui) n chnh l plasmid ti mt lc no
n hi qui thnh virus gy ung th. K thut gen hin nay ngi ta c th a bt k 1 gen
no vo t bo bng cch a vo plasmid ri t plasmid a vo DNA ca t bo.
RNA ch yu l chui n (tr RNA ca onconavirut l c xon kp) v phn b ch
yu t bo cht, trong nhn t bo c m-RNA c hnh thnh trong qu trnh sao chp m
di truyn ri t nhn ra t bo cht kt hp vi riboxom tham gia vo qu trnh tng hp
protein.
3.3. V chc nng: DNA cc sinh vt l vt cht cha bn mt m di truyn, cn
RNA thc hin vic truyn t bn m di truyn trong qu trnh sinh tng hp protein. mt
s loi siu khun c cha RNA l bn m di truyn. Lung thng tin di truyn c Crik
ra nm 1967, nm 1970 c Temin b sung nh sau:

3.4. RNA t bo ng vt li c chia lm 3 loi:
C 3 loi acid ribonucleic trong cc t bo l RNA thng tin (m-RNA), RNA ribosome
(r-RNA) v RNA vn chuyn (t- RNA). Mi loi RNA c khi lng phn t v tnh cht
base khc nhau. (Bng 2.4)
Bng 2.4: c tnh ca RNA E.coli
Loi RNA Hng s lng Khi lng phn t S gc
Nucleotide
% tng s
RNA t bo
m-RNA
t-RNA
r-RNA
63-25-3s
63-4s
5s
16s
23s
25 000-1000 000
23 000-30 000
23 000-35 000
23 000-550 000
23 000-1 100 000
75-3000
75-9s
75-100
75-1500
75-3100
2
16
82
82
82
Tt c RNA ny u l 1 si polynucleotide. Ba loi RNA ca cc loi c phn t khc
nhau: RNA ribosome (tn ti 3 loi chnh); RNA vn chuyn (hn 600 loi) v RNA thng
tin (c hng trm hng ngn loi). Trong hu ht cc t bo, RNA nhiu hn DNA t 5 n 10
ln. Cc t bo vi khun, gn nh tt c RNA tm thy trong nguyn sinh cht. Trong nhn t
bo gan c khong 11% tng s RNA (phn ln giu m- RNA), gn 15% trong ribosome
(phn ln RNA) v khong 24% trong dch bo tan (phn ln t - RNA). RNA c trong cu to
ca tt c cc virus thc vt, trong virus khm thuc l c bit r nht. RNA cng c
tm thy trong mt virus ca vi khun nh thc khun th Q ca E.coli, v mt s virus
ng vt nh poliomyelidis.
ADN ARN Protein
ADN ARN Protein
( Crik, 1967)
(Temin,1970)
3.4.1. RNA thng tin (m-RNA) ( Messenger - RNA): T l loi ny chim 2-3% trong
t bo. N c tng hp trong nhn t bo vi t cch l nhng bn sao chp bn m di
truyn gc l DNA tc l chui phn b 4 gc kim trong m-RNA lp li mt cch chnh xc
chui phn b 4 gc kim trong DNA i xng ng ra lm khun mu, ch khc l T trong
DNA c thay bng U trong m-RNA.
V cu trc ca m-RNA khi mi c tng hp c cu trc nh sau:
Intron

G
7
PPP --- CAP------ ------- -----------------polyA
Extron
u 5 ca m-RNA c cu trc c bit gi l m(cap), cu trc ny gm 1 gc G
methyl ho v tr 7, v tr 5 ca nucleotide ny c 3 gc phosphate (7m G5ppp), gc
phosphate cui cng kt hp vi 5 ca nucleotide trc n, base ca nucleotide ny l A( i
khi l G), methyl ho v tr 2 (Hnh 2.11). Cu trc m ny c vai tr lm tng kh nng
kt hp gia m-RNA vi ribosome v nh hng n qu trnh phin m. Cu trc m cng
gp phn lm bn m-RNA, bo v u 5 ca m-RNA khi b Enzyme phn gii, y cng l
ni gn protein iu ho qu trnh sao chp. Extron l on c ngha, Intron l on v ngha.
on poly A u 3, on poly A c khong 200 nucleotide Adenine, c th c vai tr lm
bn, bo v m-RNA v iu ho hot ng phin m ca m-RNA. on polyA l on kt
thc gip m-RNA qua mng nhn. Qu trnh thnh thc trc khi a ra t bo cht cc on
polyA v intron b ct b. Codon u bao gi cng l AUG m cho Met, codon kt thc l
UAG, UAA v UGA.
Lin kt
pyrophosphate
Lp 2 methyl ho thnh
thong b methyl ho)
7 - Methyl -Guanine
Cap 0 methyl
ho
Lin kt 5', 5' -
Triphosphate
Cap ethylho(thnh
thong b meyyl ho)
Hnh 2.11. 7-MethylGuanine u m 5 tm thy hu ht cc m-RNA cc sinh vt
nhn chun.
3.4.2. RNA ribosome (r-RNA).
r-RNA chim khong 65% trong riboxom v 80% tng s RNA ca t bo. C th tch
chit r-RNA t ribosome ca E.coli bng phenol, n c dng thng v phn t si n, c 3
loi vi hng s lng: 23s, 16s v 5s. Chc phn ca chng trong ribosome cha r rng, c
th chng c vai tr cu trc l thnh vin cu to nn riboxom - mt chic "my' trong qu
trnh tng hp protein. Chng c 4 loi Base chnh l A,G,C v U. Mt vi base b methyl
ho.
t bo nhn chun, trong ribosome c 4 loi r-RNA: 18s, 28s, 5.8s, v 5s. r-RNA ca
cc Ribosome trong ty th, lc lp khc vi r-RNA ca Ribosome trong t bo cht.
3.4.3. RNA vn chuyn (t-RNA) (trans RNA) cn gi l s-RNA (RNA ho tan): trong t
bo t-RNA chim khong 20% tng s RNA, c vai tr vn chuyn c chn lc cc acid amin
c hat ho ti khu vc sinh tng hp protein v nh v tr cho cc acid amin trong
chui polypeptide thng qua phn anti codon (codon i m) trong cu trc ca n.
Khi lng phn t ca t-RNA t 23.000-30.000, hng s lng t 4s -63s, c 75 n 90
nucleotide. Mi mt loi acid amin trong phn t protein c t nht 1 t-RNA tng ng vn
chuyn n, mt s acid amin c nhiu t-RNA, th d: Leucine, Serine trong E.coli c 5 phn
t t-RNA. t-RNA c th tm thy dng t do hay lin kt vi acid amin tng ng. Dng
lin kt ca t-RNA l do nhm carboxyl ca acid amin c ester ho vi nhm 2-OH hoc
3-OH ca gc acid adenilic cui cng u cui 3 ca chui polynucleotide ca t-RNA.
t-RNA c nhiu base thiu s, chim khong 10%. Cc base ny l nhng dng c
methyl ho hoc nhng dn sut ca chng. Trong t-RNA cn c nhng mononucleotide
khng bnh thng nh acid pseudouridilic v ribothymidilic. Acid pseudouridilic c lin kt
glycoside v tr 5 ca Uridine, khc vi v tr 1 nh thng thng. Acid ribothymidilic cng
khng bnh thng, v thng thng thymine c trong DNA.

u cui 5 ca t-RNA c gc acid guanilic, nhm 3-OH lin kt vi nucleotide p
cht, nhm 5-OH lin kt vi nhm phosphate. u 3 ca t-RNA lun c 3 nucleotide:
Acid pseudouridilic Acidribothymidilic
CCA. Nhm 5-OH ca gc acid adenilic lin kt vi gc acid cytidilic trc, cc nhm v tr
2 v 5-OH t do. Cu trc chung ca t-RNA c th vit nh sau:
5-pG (pN)
75-90
p
C
p
C
p
C
A-3-OH.
NHm 2-OH v 3- t do ca gc acid adenilic cui cng trong phn t t-RNA c
ester ho vi -acid amin bng Enzyme, to thnh dng hot ng hay dng vn chuyn, gi
l aminoacyl t-RNA.
Gc acid amin ny c vn chuyn n u cui sinh trng ca chui peptide trn b
mt ribosome.
Mt na s nucleotide ca phn t t-RNA bt cp to thnh nhng on xon kp. Cu
trc khng gian ca t-RNA c dng hnh ch L (hay l hnh c ba l) v chia lm 5 thu (hnh
2.12)
Thu acid amin l u 3- OH ca t-RNA c 3 nucleotide CCA, l ni lin kt vi acid
amin m n vn chuyn.
Thu TC lun c 3 nucleotide l: Ribothymidilic, Pseudouridilic, v cytidilic, thu
ny gip cho t-RNA nhn bit riboxom ang hot ng cn acid amin no.
Thu thm c th c hoc khng c trong cc phn t t-RNA khc nhau. Chc nng
cha r.
Hnh 2.12. Cu trc hnh c
ba l ca t-RNA
Thu i m (anticodon) c cha 3 nucleotide lin kt vi 3 nucleotide m (codon) trn
m-RNA. N quyt nh cho vic gn acid amin vo trong chui peptide theo nguyn tc b
xung gc kim.
Thu G
*
GA lun lun c nucleotide dihydrouridilic, l ni bm vo riboxom
4. Mt s tnh cht ca acid nucleic.
Acid nucleic l nhng cht c mu trng, khng tan trong nc nhng tan trong dung
dch mui. Dung dch acid nucleic c nht cao, c hot ng quang hoc. Acid nucleic tch
in m nn trong in trng di chuyn v cc dng.
Acid nucleic hp th mnh vng nh sng t ngoi c bc sng 250-280nm, v hp
th cc i 260nm. S dng tnh cht ny nh lng acid nucleic v xc inh sch
ca ch phm.
Khi un dung dch acid nuclieic ln 60-90C, phn t DNA xon kp b tho ri do cc
lin kt hydro gia cc base purine v pyrimidine b ph v. hp th bc sng 260nm
tng ln. S tng hp th ny gi l hiu ng hypecrom. Nhit lm mt i mt na cu
trc xon kp ca phn t DNA gi l nhit nng chy vit tt Tm (melting
temperature). Cc phn t DNA giu cc base G-C c Tm cao hn loi DNA giu A-T.
Nu dung dch acid nucleic sau khi b nng chy, c lm lnh t t th nht
dung dch gim, ng thi gim kh nng hp th nh sng bc sng 260nm gi l hiu
ng hypocrom. iu ny biu hin kh nng phc hi cc lin kt hydro gia cc cp base b
sung sau khi lin kt hydro ca chng b ph v.
DNA phn ng vi thuc th Fucsin to nn mu (Phn ng Feulgen) phn ng ny
c s dng trong ho t bo.
phn bit DNA v RNA, dng phn ng vi thuc th orcin vi RNA c mu xanh
m hn DNA.
5. Phc hp acid nucleic-protein.
Mt s acid nucleic gn vi cc protein c bit to thnh nhng phc hp c bit c
nhng chc nng ring. Trong ch yu l ribosome v Virus.
5.1. Ribosome.
Ribosome ca cc t bo nhn x c 60-65 % r-RNA v khong 45-40% protein. Trong
cc t bo nhn chun c khong 50% r-RNA v 50% protein. Trong t bo E.coli, Ribosome
c tm thy dng t do trong nguyn sinh cht v chim khong 35% khi lng kh ca
t bo. T bo E.coli c khong 15.000 Ribosome, mi mt Ribosome c khi lng 2.6 kDa
v ng knh l 180 A (Hnh 2.13). Cc ribosome cng c tm thy bn trong nhn t bo
v trong cc c quan t nh ty th v lp th. Nhiu Ribosome c hp ph thnh chui di
gi l Polyribosome hay polysome, chng l s kt hp gia mt s Ribosome vi phn t
RNA thng tin.
Cc ribosome ca tt c cc t bo c cu to ging nhau v cha r-RNA. Chng c 2
tiu phn c kch khc nhau (Hnh 1.13) Ribosome vi khun E.coli c hng s lng 70s, c
cc tiu phn 30s v 50s (Khi lng phn t ~1 triu v ~ 1.8 triu) Tiu phn 50s c phn
t r-RNA 23s, 5s, v 30 chui polypeptide, tiu phn 30s c phn t r-RNA 16s v 20 chui
polypeptide. Ribosome trong nguyn sinh cht t bo nhn chun ln hn trong t bo nhn
x, chng hp ph trn li ni cht, hng s lng l 80s, ng knh 220A khi lng phn
t 4kDa c 2 tiu phn 60s v 40s. Tuy nhin kch thc cc tiu phn thng khc nhau gia
ng vt v thc vt. r-RNA thc vt c loi 25S v 16S hoc 18s, ng vt c loi 26s v
18s. r-RNA 28s ca ng vt c kch thc khc nhau nhng loi khc nhau ph thuc vo
mc tin ho nh nhm bin l 1,4kDa v 1,75 KDa nhng ng vt khc. Ribosome
c n nh trong dung dch c nng Mg
+2
cao. Khi nng Mg
+2
gim, cc tiu phn b
tch ri nhau.
5.2. Virus.
Virus c cu trc ngng ca ca s sng, l hp cht siu phn t gia acid nucleic v cc
tiu n v protein vi s sp xp 3 chiu. Virus c khi lng ht v cng ln, chng c th
c tch chit dng ng th hoc dng kt tinh. Virus tch chit dng tinh sch khng
c kh nng ti sinh. Tuy nhin, khi ht virus (cng gi l viron) pht trin bn trong t bo
vt ch, n c kh nng iu khin s sao chp ring ca mnh. Acid nucleic vurus l phn
nhim ca ht virus.
C ch tng hp cc phn t ca virus khc vi cc phn t ca cc t bo ch bnh
thng. RNA ca virus buc ribosome t bo vt ch hot ng nh l khun cho s tng hp
cc protein v virus v cc Enzyme cho s sao chp cc hp cht khc ca cu trc virus.
DNA ca cc virus nh l khun cho s sao chp cc phn t m-RNA b sung, n li
chim ot b my ribosome v tin hnh tng hp cc Protein virus v cc Enzyme cn thit
cho tng hp DNA virus. Cc virus c kch thc, hnh dng v thnh phn ho hc khc
nhau (bng 2.5). Trong mt s virus, th d virus khm thuc l, ch tn ti loi tiu phn
protein n. Nhng loi protein khc (th d thc khun th T
2
ca Ecoli) c th c nhiu loi
tiu n v Protein v hay capsid ca virus c to thnh nhm cc tiu phn protein gi l
Hnh 2.13. Cu trc ca Ribosome
Capsomere (n v hp thanh capsid). Acid nucleic ca virus hay xy ra s methyl ho cc
base
Bng 2.5. Khi lng, kch thc v hnh thi ca acid nucleic mt s virus
Tn Khi lng ht
(dalton)
Acid nucleic v
s chui
% acid
nucleic
Hnh dng Chiu di
(A )
Thc khun th Ecoli
T
2
,T
4
,T
6
,
T
7
c174
MS2
Virus thc vt khm
thuc l
Bushu stunt c chua
Gy cht li thuc l
Virus ng vt: Bi
lit tr em
Polioma (virus gy
ung th ng vt
gm nhm)
Adenovirus
u ma
220 000 000
38 000 000
6000 000
50 000 000
3 600 000
40 000 000
10 600 000
1 970 000

6 700 000
21 000 000
200 000 000
2 000 000 000
DNA(2)
DNA(2)
DNA(1hoc2)
DNA(2)
RNA(1)
RNA(1)
RNA(1)
RNA(1)
RNA(1)
DNA(2)
DNA(2)
DNA( `)
61
41
26
64
32
5
15
20
28
13.4
5
7.5
Nng nc
Nng nc
Nhiu mt
Nng nc
Nhiu mt
Que
Nhiu mt
Nhiu mt
Nhiu mt
Nhiu mt
Nhiu mt
Vin gch
180
60
150
200
175
3000
280
210
300
450
700
2300
Hnh 2.14: nh knh hin vi in t ca cc virus, s virus khm thuc l.

Cc tiu phn
Protein
C
u
ui
Ru
Hnh 2.14
nh kinh shin vi in t ca
Cu trc ca
Th th kh T i
0,1
0,1
0,1
Tt c virus thc vt l loi RNA, c dng hnh que, xon kp, nh virus khm thuc l,
hoc c dng 20 mt nh virus bushustunt c 60 caspomere (nhm cc tiu phn protein) mi
mt c 3 tiu n v c sp xp theo kiu i xng. Virus ng vt c th l DNA hoc
RNA. Mc d mt s nh virus polimelidis (gy bi lit tr em) rt nh, song hu ht chng
u ln hn virus thc vt. Virus vi khun (gi l thc khun th) l mu vt thch hp
nghin cu, v chng tin hnh sao chp mt lng ln trong vi khun v d tch chit. Virus
vi khun quan trng nht l ca cc t bo E. coli nh th thc khun th T
2
,T
4
,T
6
, T
7
x174
v . Cu trc ca virus c nghin cu rt t m bng knh hin vi in t v s nhiu x tia
x. Cu trc ca 1 vi virus c gii thiu hnh 2. 14
6. Trao i acid nucleic.
Acid nucleic l vt cht di truyn ca c th sng, iu ho qu trnh sinh tng hp
protein. Mt s nucleotide l thnh phn coEnzyme quan trng. V vy, nghin cu qu trnh
trao i acid nucleic c ngha i vi cc c th sng.
6.1. S phn gii acid nucleic (s thu phn acid nucleic)
Di tc dng ca nuclease, acid nucleic b thu phn to thnh cc mononucleotide v
oligonucleotide. ng vt, acid nucleic b thu phn t trng di tc dng ca nuclease
tuyn tu. nim mc rut c diesterase thu phn oligonucleotide thnh mononucleotide.
Nuclease c th chia lm 2 nhm: Endonuclease v exonuclease.
a) Endonuclease: Ct cc lin kt diester bn trong chui polynucleotide. N c chia
lm 2 nhm: Ribonuclease (RNAase) xc tc phn gii RNA, Desoxyribonuclease (DNAase)
xc tc phn gii DNA.
b) Exonuclease: Xc tc cho qu trnh phn gii ln lt tng nucleotide ra khi chui
polynucleotide.
6.1.1. Phn gii mononucleotide:
Cc mononucleotide c hnh thnh khi phn gii DNA v RNA hoc c s dng
tng hp li acid nucleic, cc hp cht cao nng v cc coEnzyme v.v... hoc tip tc b
thu phn di tc dng ca nucleotidase (phosphatease) c trong rut to thnh cc
nucleoside v acid phosphoric. cc m gan, thn, lch c nucleotidase, cc nucleoside b
thu phn thnh base nit v pentose.
6.1.2. Phn gii base purine v pyrimidine.
Phn gii purine: S thoi ho cc nucleotide purine c nghin cu k. Adenine,
nucleoside v nucleotide ca n c th deamin ho thu phn di tc dng ca cc Enzyme
deaminase, adenoseine deaminase v adenilate deaminase to thnh hypoxanthine, inoseine
hoc inoseine monophosphate tng ng (hnh 2.15) v nucleotide Guanine cng phn gii
tng t di tc dng ca Guanine, guanoseine v guanylat deaminase to thnh xanthine
hoc dn xut ribose ca chng (hnh 2.15)
ngi v vn ngi sn phn cui cng ca s phn gii ny l acid uric, n c thi ra
ngoi cng vi nc tiu, cn ng vt khc, phn ln hoc hon ton acid uric bin i thnh
allaintoin. ng vt mu lnh c, lng th v trong nhiu ng vt c, allaintoin phn li thnh
acid glyoxylic v ur.
a s thc vt, cc base purine phn gii thnh ure allaintoin v acid allantoic nh s
xc tc ca allatoicase, cn ur phn gii thnh CO
2
v NH
3
di tc dng ca Urease.
Hnh 2.15: S thoi ho ca purine mc nucleotide, nucleoside v
basehypoxanthine, xanthine sau b oxy ho di tc dng ca xanthine oxydase to
thnh acid uric.
Phn gii pyrimidine: S phn gii nucleotide pyrimidine ging nh nucleotide purine
bao gm dephosphoride ho, deamin ho v ct lin kt glicoside. Nhiu phosphatease tc
dng ln nucleotide purine cng tc dng ln cc dn xut pyrimidine tng ng, nucleotide
pyrimidine b thu phn thnh cc base pyrimidine v ng, hoc chng c th bao gm c
s ct phosphrolytic cytosine, c th deamin ho bi cytosine deaminase xy ra nm men v
nhng vi sinh vt khc. Nucleoside cytidine b phn gii thnh nucleoside uridine bi cytidin
deaminase ph bin cc m ng vt cng nh vi khun.
Adenine
deaminase
Adenine
deaminase
Poxathine
xanthine
oxydase
Guanine
deaminase
Guanine
xanthine
xanthine
oxydase
Con ng phn gii uracil v thymine cc m ng vt bao gm s kh pyrimidine
thnh dn xut dihydro, m vng thnh acid ureidoisobutilic tng ng gii phng
amoniac v CO
2
to thnh -alanine hoc dn xut methyl ho ca n (hnh 2.17).
6.2. Sinh tng hp acid nucleic.
6.2.1. Sinh tng hp nucleotid purine
c th ng vt c th tng hp c purine v pyrimidine, nhng i vi mt s vi
sinh vt pht trin bnh thng cn phi c mt lng purine v pyrimidine trong mi
trng dinh dng.
Nucleotide purine v pyrimidine c th c tng hp mi t nhng tin cht nh acid
amin, NH
3
, CO
2
, acid formic. Bng phng php nguyn t nh du ngi ta bit c
ngun gc cc thnh phn cu to nn nhn purine (hnh 2.18).
Nguyn liu ban u trong sinh tng hp purine l 5-phosphoribozil 1-
pyrophosphate (PRPP), (hnh 2.19) n nhn nhm amin ca glutamine to thnh 5-
phosphoribozil amin (PRA). Di nh hng ca Enzyme phosphoribozil pyrophossphate
amidotransferase (amidophosphoribozil transferase).

Uracil Dihydro uracil acid - Ureidopropionic . Alanine
Thymine Dihydro thymine acid - Ureidosobutiric Acid - amin izobutiric
Hnh 2.17. Cc con ng phn gii Uracil v Thymine
Hnh 2.21: S to thnh AMP v GMP t IMP.

Glutamine
Glutamate
methyl
Formyl
GAF
Glutamine
Glutamat
Glycine
Succino - Aicar Aspartate Carboxy AIR Focmyl GAM

Fumarate
Formyl
AICAR Focmyl AICAR
+ GTP
+ Aspartate
Acid
denilsuccinic
Adenilo - Succinat
lyase
Fumarate
NAD
c ch bi acid
micophenolic
xantosein 5' -
phosphate (XMP)
Glutamine
GMP
Uracil --> Dihydrouracil - acid - Ureidopropionic --> -alanine
Thymine --> Dihydrothymine - acid - Ureidopzobutiric --> - aminizobutinic
Hnh 2.20. Sinh tng hp
nucleotid purin
Sau phn ng vi PRA to thnh glycinamide Ribonucleotide (GAR) phn ng tip
theo bi formin ho t acid N
5
, N
10
- methyl-tetradrofolic thnh formyl glycinamide
ribonucleotide (formyl-GAR). Sau amin ho nhn t glutamine cho formyl-glycinamide
ribonucleotide (formyl-GAM), chu trnh c ng li to nn hp cht vng imidazol l 5-
aminimidazol ribonucleotide (AIR). Carboxyl ho hp cht ny to thnh acid 5-amin-
imidazol-4-carboxylic ribonucleotide (cacboxy-AIR). Amide tng ng l 5-aminimidazol-4-
carboxamide ribonucleotide (AICAR) c to thnh qua 2 phn ng vi hp cht (hnh
2.20).
Amin ho IMP thnh AMP tin hnh qua 2 bc vi s to thnh hp cht trung gian
acid Adenine succinic (hnh 2.21).
Trong phn ng ny nhm amin ca Aspartate c chuyn n C-6 ca IMP to
thnh AMP.
S to thnh GMP t IMP cng phn ng qua 2 giai on, trong xantoseine 5-
monophosphate (XMP) c to thnh trc, sau l GMP (Hnh 2.21)
Hai mononucleotide purine AMP v GMP b phosphoryl ho bi kinase qua giai on
diphosphate cho ATP v GTP
AMP + ATP <---> ADP + ADP
GMP + ATP <---> GDP + ADP
ADP + ATP <---> ATP + ADP
GDP + ATP <---> GTP + ADP
Ngoi cc con ng k trn, cc nucleotide cn c th c tng hp t cc base
purine kt hp vi ribose-1- phosphate di s xc tc ca nucleoside phosphoridase tng
ng to thnh cc nucleotide v acid phosphoric. Cc phn ng ny thuc kiu
transglycosil ho
Hypoxanthine + Ribose-1-phosphate <---> inosine + PVC
Guanine + ribose-1-phosphate <---> guanoseine + PVC
Cc nucleotide c hnh thnh li b phosphoryl ho vi s xc tc ca phosphokinase
(phosphotransferase) to thnh nucleotide tng ng.
Adenoseine + ATP <---> AMP + ADP
Ngoi ra cc purine t do kt hp vi PRPP di tc dng ca nucleotide
pyrophosphate kinase (chuyn gc phosphoriboseil) to thnh cc nucleoside 5- P
Adenine + PRPP <---> AMP + PP (Pyrophosphate)
Guanine + PRRP <---> GMP + PP
Hypoxanthine + PRPP <---> IMP + PP
6.2.2. Sinh tng hp nucleotid pyrimidine
Khc vi sinh tng hp nucleotide purine, chu trnh pyrimidine c tng hp trc ri
kt hp vi ribose 5- phosphate. Bng phng php nguyn t ghi du xc nh c
ngun gc ca cc nguyn t to nn pyrimidine (hnh 2.22).
S tng hp UMP c hng lot cc phn ng Enzyme xy ra to thnh mononucleotide
pyrimidine u tin (Uridine 5-monophosphate, UMP) c gii thiu hnh 2.23. Trc
tin l acid aspartic kt hp vi carbamoyl phosphate vi s xc tc ca carbamoyl
transferase to
thnh carbamoyl aspartate. Sau
vng pyrimidine c hnh thnh do
dihydro-orotase to nn acid dihydro-
orotic, tip tc dehydrogenase ho to
thnh sn phm pyrimidine trung gian
quan trng l acid orotic. Di tc
dng ca pyrophosphoridase, acid-
orodic lin kt vi gc ribose-5-
phosphate t PRRP to nn Oridin 5-
monophosphate (OMP) v gii phng
pyrophosphate. Decarboxyl ho OMP
to thnh Uridine 5-monophosphate
(UMP) l nucleotide pyrimidine u
tin .
Hnh 2.22: Ngun gc cc nguyn t trong
chu trnh pyrimidine
Hnh 2.23. Con ng sinh tng hp pyrimidine

Hnh 2.23. S to thnh pyrimidine.
UMP di tc dng ca kinase bin i qua uridine 5-P (UDP) thnh uridine 5-
triphosphate (UTP)
Sinh tng hp dn xut cytosine.
S bit i uracil thnh cytosine giai on nucleoside triphosphate do Enzyme CTP
syntheta xc tc
Amoniac
Co
2
Aspartate
N
C
Glutamin
Carbamoyl Carbamoyl Dihydro-orotate Orotate
phosphate aspartate
Orotidic5' -
monophosphate
(OMP)
UTP + NH
3
+ATP ---> CTP + ADP + PVC
6.2.3. Sinh tng hp desoxyribonucleotide
S bin i ribose thnh desoxyribose xy ra mc nucleotide, khng lm t lin
kt glycoside.
E.coli s dng c cht l ribonucleoside diphosphate, Lactobacillus leichamnii s
dng ribonucleoside phosphate v i hi Enzyme cobam. S hiu bit v c ch bin i
trong t bo ng vt khng nhiu, nhng hnh nh khng cn cobamide v ging vi E.coli.
C ch s bin i CDP thnh dCDP trong Ecoli c h Thioredoxyn. Thioredoxyn l
protein c cha lu hunh vi 108 gc acid-amin, n c kh bi NADPH di tc dng
ca Thioredoxyn reductase. Thiredoxyn kh CDP thnh dn xut desoxy, n t loi oxy n
Thioredoxyn.
dUMP c hnh thnh bi deamin ho dCMP di tc dng ca dCMP deaminase.
Con ng bin i y t UMP thnh dUMP c th nh sau:
UMP ---> UTP ---> CTP --->CDP ---> dCDP ---> dUMP
E.Coli khngc dCMP deaminase, dUMP c hnh thnh t UMP bi ng vng
sau:
UMP ---> UDP ---> dUDP --->dUTP ---> dUMD (Hnh 2.24)
6.2.4. Sinh tng hp cc dn xut thymine.
Cc bc c bn trong s to thnh nucleotide thymine l s methyl ho desoxyuridine
monophosphate (d UMP) thnh sn phm thymidine monophosphate (d TMP) (d UMP d
TMP) di tc dng ca Enzyme Thymidilate synthetase. Qu trnh xy ra qua mt s giai
on. Ngun cho nguyn t carbon C-5 l acid N 5, N 10- methylen tetra hydrofolic, phn
ng nh sau:
N
5
, N
10
-methylen tetrahydrofofate+ d UMP---> dihydrofolate + d TMP
Dihydrofolate li to thnh tetrafolate di tc ng ca hydrofolate reductase.
S to thnh nucleoside triphosphate.
PRPP Glutamine Aspartate Carboamoyl phosphate
Khng
Azaserin v
acid folic
+ glicine
+ Glutamine
+ Aspartate
Carbo
Azaumaxil
Fluorodexi eridin
Khng acid folic
Hnh 2.24: Con ng phc tp sinh tng hp desoxyribonucleoside triphosphate. C ch s
dng li biu th bng ng chm. Hot ng c ch ca mt s chng phn gii bng nt m.
Trong sinh tng hp DNA v RNA cn c cc ribonucleoside 5-triphosphate v
desoxyribonucleoside 5-triphosphate, chng c hnh thnh t cc nucleoside
monophosphate tng ng bi cc Kinase thch hp vi s c mt ca ATP. giai on ny,
cc Kinase quan trng l bin i thymidine thnh triphosphate ca n (dTTP). S bin i
ny qua bc thang phosphoryl ho. Mi bc c xc tc bi mt kinase ring.
Thymidine ---> d TMP ---> d TDP ---> d TTP.
6.2.5. Sinh tng hp acid desoxyribonucleic (DNA).
Sinh tng hp DNA l qu trnh sao chp chnh xc phn t DNA u tin. Trn c s
m hnh phn t DNA ca Watson v Crick. S ti to DNA xy ra bng cch lin kt hydro
gia 2 chui b sung b t v tch ri nhau ra. Mi mt chui c kh nng kt hp vi cc
desoxyribonucleotide triphosphate t do, to thnh chui polyribonucleotide mi khp hp
vi chui ban u. DNA mi ging vi DNA ban u v thnh phn v trt t cc nucleotide .
C ch sao chp bn bo tn.
Qu trnh t sao, mt si gi nguyn, mt si mi c tng hp c gi l c ch sao
chp bn bo tn, iu ny c Meselson v Stahl chng minh bng cch nui E.coli
trong mi trng c nit nh du
15
N (
15
NH
4
Cl), DNA c tng hp ch cha
15
N. Sau
nui cy mi trng
14
N th thy DNA th h th nht l dng lai, gm mt si
15
N v
mt si
14
N. Th h th 2 c 50% DNA dng lai v 50% dng ch c
14
N (cc bng ca DNA
tm thy bng li tm nng C
s
Cl) (Hnh 2.25, 2.26)
Hnh 2.25: Cc bng DNA ca th nghim Meselson v Stahl.
C ch ca qu trnh t sao DNA.
Enzyme tng hp DNA. Nm 1956, Kornberg tch c Enzyme DNA polymerase
t E.coli. Enzyme ny c kh nng xc tc qu trnh tng hp DNA t cc
desoxyribonucleoside triphosphate. Sau ngi ta tch c Enzyme ny t vi khun,
thc vt v ng vt.
DNA polimenase xc tc s to thnh lin kt phosphodiester gia nhm 3-OH u
sinh trng ca chui DNA (mi) v nhm 5-phophate ca desoxyribonucleoside
Nh hn
Nh
Trung bnh
Nng
Nng hn
triphosphate mi (hnh 2.26) s sinh trng theo chiu 5-->3. Trong qu trnh ny c DNA
lm khun. DNA khun thc hin nguyn tc ghp i b sung: A-T, C-G (hnh 2.27).
Cc giai on sinh tng hp DNA
M xon: di tc dng ca DNA derulase, xon kp DNA c m c 1 loi protein
SSB (Single StDNA Binding) gn vo si n DNA phn t DNA lun dng m.
Tng hp RNA mi: Da vo khun si n DNA, mt on RNA mi c tng hp
vi s xc tc ca RNA-polymerase.
S ko di si DNA: Sau khi c RNA mi, RNA mi s to ra nhm 3-OH t do,
sau DNA polymerase bt u hot ng ti bn.
Mi mt nucleoside triphosphate c ghp vo bng lin kt phosphodiester C-5,
chiu tng hp l 5---> 3. Nh vy c 1 si c tng hp lin tc gi l si hng dn, cn
si kia tng hp tng on ngn cng vi s m xon, gi l si i theo. Tng on ngn
gi l on Okazaki (tn nh bc hc Nht bn pht hin chng E.coli c cng b nm
1968). E.coli on ngn ny c hng s lng 8-10s, chiu di 1000-2000 nucleotide, on
10s c th c to thnh t vi on 3-5s. t bo ng vt on ny ngn hn nhiu, n
c
khong 100-200 gc nucleotide, hng s lng 4-5s. giai on ny RNA mi c loi b
bi endonuclease, v on c tng hp li bi DNA polymerase. Cc on Okazaki
c ni vi nhau bng DNA-ligase (Hnh 2.28; 2.29; 2.30).
6.2.6. Sinh tng hp acid ribonucleic (RNA).
(dNMP)
n
+dNTP PP dNMP
n
Mg
+
+
+
1
) (
2
DNA Polimerase
DNA mi
Hnh 2.27. S sinh trng ca DNA
K
h
u
n
M
i

Hnh 2.26. C ch hot ng ca
DNA Polimerase
S biu hin thng tin di truyn l s truyn tn hiu t DNA sang RNA. Nhn chung,
si RNA c th hon ton ging vi si DNA ch khc l c nhm hydroxyl v tr 2 v
uracil thay bng thymine, song RNA c cu trc a dng hn DNA v km theo s khc nhau
v chc phn. Phn t RNA khng th hng dn v thng tin nhanh chng di truyn nh
DNA, RNA cn c th hot ng nh l cht xc tc.
S pht hin ra RNA cn c chc phn xc tc lm thay i rt nhiu ca t
Enzyme. Nhiu RNA l phc cht ca protein, to nn c ch phc tp vi nhiu chc phn
khc nhau.
Hnh 2
Hnh 2.28: Ti bn DNA Hnh 2.30. Chc ba ti bn
Hnh 2. 30. Cc on Okazaki ni vi nhau
RNA
mi
5
Hnh thnh Tng hp Ct ri RNA v

1 si RNA DNA mi thay th bng DNA
Hnh 2.29. Khi u ti bn RNA Polimenrase
5
im khiu 5
im khiu
3
RNA polymerase ph
thuc DNA
m xon
chui DNA
Enzyme derulase
RNA mi
Mi th 1
Mi th 2
Tng hp DNA bi
DNA - plimerase
RNA RNA mi
mi hnh thnh
Loi b RNA mi bi
endonaclease hnh thnh
on okaseki
Ni li bi
Ligase
Relicase
DNAlin kt
protein (SSB)
Primenson
Primenson
Primase
Mi
HoloEnzyme
DNA
Polymerase
III
DNA
Polymerase I
Ligase
Si dn
ng
Si i
theo
Tng hp RNA ph thuc DNA.
sinh vt nhn x (procaryote) ch c 1 loi Enzyme RNA polymerase ph thuc DNA
thc hin s sao chp.
sinh vt nhn chun (Eucaryote) c 3 loi RNA polymerase, mi loi c 1 chc nng
ring. Phn t RNA c hnh thnh trong nhn, sau chuyn ra t bo cht hot ng.
S sao chp RNA ch thc hin trn 1 si ca DNA, hng sao chp t 5-P -->3-OH. RNA
-Polymerase xc tc tng hp RNA t cc ribonucleotide 5-phosphate (ATP, GTP, UTP v
CTP). S tng trng si RNA bng cch kt hp cc ribonucleotide u 3-OH ca chui
RNA
(MMP)
n
+ NTP ---> (MMP)
n+1
+ PP
RNA Ko di RNA
Hnh 2.31. S sao chp RNA
S sao chp ch xy ra trn 1 si DNA lm khun, mi 1 nucleotide lin kt to
thnh RNA mi c la chn theo nguyn tc cp base b xung Watson-Crick. Uridine (U)
trong RNA i din vi Adenine (A) trong khun DNA, Adenine i din vi Thymine,
Guanine v Cytosine trong DNA i din vi Cytosine v Guanine trong RNA mi.
RNA polymerase
Tho xon
Si khng
lm khun
Bong bng phin m
RNA-DNA lai Si khun
Hng phin m
Siu xon m Siu xondng
Hng phin m
Si DNA dng lm khun cho tng hp DNA gi l xi khun hay si tr (-). Si
Khc vi DNA polymerase, RNA polymerase khng cn mm khi u tng hp. S
khi u tng hp 1 on c bit gi l gen khi u (RNA c tng hp vn c 5-
triphosphate) gc GTP v ATP trong qu trnh phin m). Trong qu trnh phin m to
thnh on xon kp gia RNA v DNA khun gi l on xon kp lai RNA-DNA (hnh
2.32a). RNA trong si xon kp ny li c tch ra khi DNA.
S tng hp RNA xy ra trn mt si DNA, nn si xon kp DNA phi tho xon,
vng tho xon phin m nh l bong bng. E.coli vng ny khong 17 cp base c
tho ri. S tho DNA pha trc v cun li pha sau. Qu trnh ny lm cho phn t
DNA quay ng k (hnh 2.32 b), nu quay v pha trc chui l siu xon dng, v nu
quay v pha sau l siu xon m. E.coli s phin m vi tc 50 nucleotide 1giy.
DNA b sung vi si khun gi l si khng lm khun hay si cng (+), cc base ca
n rt ging vi RNA c phin m ch khc U thay T. Si khng lm khun thnh thong
cn gi l si m ho (hnh 2.33)
(5) CGCTATAGCGTTT (3) si DNA khng lm khun (+)
(3) GCGATAT CGCAAA (5) Si DNA khun (-)
(5) CGCUAUAGCGUUU (3) RNA phin m.
Hnh 2.33: Hai si b sung ca DNA c xc nh r chc phn trong phin m.
Cu trc v hot ng ca RNA polymerase.
Ecoli RNA polymerase n ph thuc DNA tng hp cc loi RNA kh ln (KLPT:
390.000) phc cht Enzyme ny c 5 tiu n v l li Enzyme v 1 tiu n v th 6 l
(xch ma) hy 70 (KLPT: 70 000) n lin kt tm thi vi mt li v hng dn Enzyme
n v tr khi u c bit trn DNA, 6 tiu n v ny to thnh holoEnzyme RNA
polymerase (hnh 2.34)

Tiu n v

Li Enzyme
TLPT: - 36.500, - 151.000,
- 155.000
- 11.000, - 70.000. Tiu phn c cho
rng l v tr xc tctng hp RNA
Hnh 2.32: S phin m bi RNA polymerase trong Ecoli.
Hnh 2.34. HaloEnzyme RNA polymerase.
Yu t cn gi l yu t khi ng (yu t mi) gn vo RNA polymerase nhn
bit m (codon) khi u sao chp. Khi bt u sao chp n s tch ri yu t (r) cn gi
l yu t kt thc. Khi kt thc th yu t c gii phng (hnh 2.35). RNA polymerase
trt trn DNA tng hp RNA theo hng 5-->3. n v tr kt thc, yu t gn vo
RNA polymerase nhn bit m kt thc v yu t c gii phng, RNA polymerase
tch khi si khun DNA.
Vng khi ng.
Hnh 2.36: 5 on gen khi u ca E.coli, cc on gen ny si m ho (khng
lm khun) v c t 5 3. Nhng vng m s lng nucleotide (N) c th thay i.
Vng 35 Vng
m
Vng-10 Vng
m
Bt u
RNA
+1
Trp TTGACA 17N TTAACT 7N A

tRNA
+
Ty
r
TTTACA 16N TATGAT 7N A
Lac TTTACA 17N TATGTT 6N A
Rec A TTGATA 16N TATAAT 7N A

Dra
B,A,D
CTGACG 18N TACTGT 6N A

on
chung
TTGACA TATAAT
S khi u tng hp RNA trn phn t DNA l vng c bit vng phn t RNA
polymerase lin kt vi DNA v c gi l gen khi u. v khun gen khi u l 2 on
ngn vi khong 10 v 35 cp base (Hnh 2.36) RNA c tng hp l +1. Cc on gen
khi u khng ging nhau, nhng cng c nhiu nucleotide chung. Phn ln cc gen khi
u ca E.coli v vi khun vng 10 (cn gi hp Pribonow) l (5) TAAAT (3) v vng
35 l (5) TTGACA (3)
m-RNA lun lun to ra AUG khi u, pha trc AUG c mt on khng ghi m
cho protein no c, ch gn vo ribosome.
Hnh 2.37: Cc giai on trong s khi u phin m bi RNA polymerase E.coli
RNA polymerase lin kt vi gen khi u cn phi 2 giai on: S to thnh ca phc h
ng v m Tng hp RNA thng tin hu nh lun lun bt u vi nucleotide purine (Pu)
N l nucleotide bt k.
RNA polymerase Gen khi u
RNA polymerase hnh thnh
phc hp ng vng -35
Polymerase di chuyn n vng - 10
DNA c tho ra to thnh phc
Si khun
Bt u tng hp RNAm
Nucleotide
triphosphate purine
NTP
PP

Tiu phn tch ra khi
polumerase vt qua khi
u
YU CU CN NM
CHNG II: ACID NUCLEIC V C CH DI TRUYN T BO
Khi nim v acidnucleic, vai tr ca cc nucleotit t do. Cu trc bc I bc II ca
acidnucleic. Phn loi acidnucleic
Cu 1: Cng thc ca ATP? Vai tr ca ATP trong hot ng sng ca ng vt?
Cu 2: Trnh by cu trc bc I ca axt nucleic? Codon, Anticodon l g? Vai tr sinh
hc ca cu trc ny?
Cu 3: Ni dung nguyn tc b xung gc kim trong chui xon kp ca axt nucleic?
ngha sinh hc ca nguyn tc ny?
Cu 4: Phn loi axit nucleic
CHNG III
ENZYME V XC TC SINH HC
1. Khi nim
Enzyme l nhng cht xc tc sinh hc, do c th sng tng hp nn. Chng xc tc
cho cc phn ng ho sinh, Nh c Enzyme m cc qu trnh ho sinh xy ra rt nhy, vi tc
rt nhanh trong nhng iu kin sinh l bnh thng (nhit c th v pH mi trng
m bo).
Enzyme c mi sinh vt, trong t bo sinh vt v l ng lc ca mi qu trnh sng.
Hay c th ni Enzyme l nhng cht m di tc dng ca chng cc phn ng ho sinh
c thc hin rt nhanh chng vi nhp iu, trnh t ht sc r rng chnh xc trong qu
trnh trao i vt cht (TVC) ca c th. Sng l TVC m TVC l t hp ca hng lot
nhng phn ng ho sinh phn gii hoc tng hp. Mi phn ng nh vy c thc hin rt
nhanh chng c khi hng nghn ln trong giy vi nhp iu v trnh t ht sc r rng v mi
phn ng c thc hin bi mt Enzyme c hiu.
Lch s Enzyme c t lu. Ngay t u th k 19 c nhng nghin cu ghi nhn
s hin din ca cht xc tc sinh hc Enzyme trong qu trnh tiu ho nc bt, d dy
v rut. Nm 1850, Pasteur nhn nh qu trnh ln men c mt yu t xc tc l
ferment. Sau ny yu t trn c gi thng nht l Enzyme. Nm 1897 ngi ta chng
minh chnh dch chit ca Enzyme ch khng phi ton b t bo nm men c kh nng ln
men ng thnh ru. l bng chng v s tham gia ca bn thn Enzyme trong qu
trnh ln men. Nm 1926, ln u tin Sammer thu c tinh th Enzyme Urease. Nm
1930 Northrop thu c tinh th Pepsin v Trypsin.
Trong giai on cui ca th k 20, cc nghin cu trong lnh vc ny c tp trung
vo vai tr xc tc ca Enzyme trong qu trnh trao i cht ca t bo. Vic tinh sch c
hng nghn Enzyme v nh vy lm sng t cc cu trc khng gian v chc nng xc tc
ca nhiu Enzyme khc nhau.
Ngy nay Enzyme cng c s dng rng ri trong y hc, cng ngh vi sinh, nng
nghip, ch bin thc phm v c trong lnh vc m phm.
2. Bn cht ca Enzyme
Enzyme l protein v chng c cu to t cc acid amin vi cc cu trc bc I, II, III, IV
nh protein v chng cng c y cc tnh cht vt l ho hc ca protein nh c tnh
keo, im ng in, hin tng sa lng... v cng b ph hu bi cc yu t nhit , acid,
kim mnh nh protein.
Enzyme l mt lp protein ng o c khp ni trong gii sinh vt, chng phn b
trong c th cng a dng, c Enzyme phn b trong t bo cht, l thnh phn cu trc ca
mng, trong ty lp th, trong mng ty lp th, c loi c nh, c loi di ng c nh trong
mu, trong sinh dch...
Ngoi tr mt nhm nh phn t RNA c hot tnh xc tc, cn tuyt i a s Enzyme
u c bn cht protein v s th hin hot tnh xc tc ph thuc vo cc bc cu trc t I
n IV ca phn t protein cng nh trng thi t nhin ca n.
Enzyme c khi lng phn t thay i rt rng t 12.000 Dal n hng triu Dal.
Mt s Enzyme th hin hot tnh xc tc khng cn s c mt ca cc yu t khc
ngoi phn t protein, l nhng Enzyme n gin.
Ngc li, nhng Enzyme phc tp, ngoi phn t protein cn c thm nhm ghp l
CoEnzyme. Phn CoEnzyme c bn cht rt khc nhau nhng trc ht v ng o hn c l
dn xut ca cc vitamin ri n cc ion kim loi ho tr 2 nh Fe
+2
, Mg
+2
,Mn
+2
, Zn
+2
Co
+2
...
Cc ion kim loi ny ng vai tr cofactor hoc cn s c mt v phi hp tc ng ca cc
phc hu c hoc phc hu c - kim loi lm yu t ng Enzyme.
Ngi ta gi phn protein ca Enzyme l apoEnzyme (hay apo-protein), cn cc yu t
khc gi l nhm ngoi Prosthetic v phc cha y c 2 yu t c gi l Enzyme hon
chnh (HoloEnzyme).
3. Trung tm hot ng ca Enzyme:
Trung tm hot ng ca Enzyme l ni tip xc gia Enzyme vi i tng tc ng
ca n (tc l c cht ), l ni Enzyme thc hin phn ng. Trung tm hot ng c hnh
thnh thng qua cu trc bc III ca phn t protein Enzyme, thng qua mt s gc acid
amin bnh thng nm xa nhau trong cu trc bc I c th c phn b li gn nhau, phi
hp vi nhau thc hin chc nng xc tc ca Enzyme. cc Enzyme phc tp th do cc
gc acid amin kt hp vi nhm ghp to nn.
V d trung tm hot ng ca chimotrypsin ca tuyn tu, t nht l bao gm gc serin
v tr 195 v gc histidin v tr 57. Nhng gc ny tuy xa nhau v cu trc bc I nhng li
gn k nhau v cu trc khng gian khi Enzyme chimotrypsinogen c hot ho bi Entero-
kinase (hnh 3.1).
Hnh 3. 1. M hnh cu trc ca Enzyme chimotrypsinogen, s hot ho Enzyme ny
l Entero-kinase ca tuyn rut
Cc gc acid amin thng tham gia vo trung tm hot ng l Cys vi nhm -SH, Ser,
Tyr, Tre vi nhm - OH; Lys, Arg vi nhm -NH
2
, Glu, Asp vi nhm COOH, His vi
nhm imidazole. Khi Enzyme c thm nhm ghp tc l coEnzyme th coEnzyme phn b
ngay trung tm hot ng.
Cng cn ch rng c nhng Enzyme c mt trung tm hot ng, nhng cng c
nhng Enzyme c hai hoc nhiu trung tm hot ng, v d alcol dehydrogenase gan c hai
trung tm hot ng, cn alcol dehydrogenase ca nm men c ti bn trung tm hot ng.
C th coi trung tm hot ng l phn quyt nh trong hot ng ca Enzyme nn mi
tc ng c nh hng ti Enzyme trc ht l nh hng ti trung tm hot ng nh hin
tng c ch, hot ho...Cc cht tc dng c th lm tng cng hot ca Enzyme th
ngi ta gi l cht hot ho, nu lm gim hoc t lit hot ca Enzyme th gi l cht c
ch. Nhng cht ny c th tc dng thng vo trung tm hot ng ca Enzyme nh mt s
ion kim loi: Cu
++
, Zn
++
, Mn
++
, Mg
++
, Co
++
, Ca
++
... c tc dng hot ho Enzyme do cc ion
ny tham gia trc tip vo trung tm hot ng vn chuyn in t hoc to thnh cu ni
gia c cht v Enzyme. Mt s cht c tc dng c ch Enzyme nh KCN, ditrec... chng c
th phng b hoc bt kn trung tm hot ng ca Enzyme
Cc yu t nh hng ti trung tm hot ng:
Nhit : l biu hin ni nng ca vt cht, biu hin s chuyn ng nhit ca cc
ion. Nhit thch hp cc Enzyme hot ng tt l nhit ca thn nhit (37-40
0
C).
Nhit cao qu lm cho chuyn ng nhit ca cc ion tng qu mnh lm t cc dy ni,
ph v cu trc bc III, do Enzyme b t lit hoc b ph hu hon ton. Nhit thp qu
(0
0
C) phn t khng chuyn ng, s va chm gia Enzyme vi c cht gim lm cho hot
tnh ca Enzyme gim hoc mt hn. Tc ng ca nhit cha su sc th Enzyme c th
phc hi nh khi nhit khng cao qu hoc thp qu. Nhit tng mc thch hp th c
tc dng kch thch hot ng ca Enzyme (st nh).
Gi tr Kcat ca tuyt i a s Enzyme gia tng khi nhit mi trng ca phn
ng gia tng cho n khi t gi tr xc nh th khng tng na v s gim hot tnh xc tc
khi nhit tip tc tng. Nhit m Enzyme t gi tr hot tnh cc i gi l nhit
ti u ca Enzyme.
pH: Mi Enzyme c mt vng pH hot ng tt nht ca mnh, ngoi vng
hot ca Enzyme b gim st hoc mt hn. Bn cht ca s nh hng ny l do nng
H
+
thay i nh hng n s phn ly ca cc gc to nn cu trc bc III ca Enzyme,
nh hng ti s phn ly, phn cc gia Enzyme v c cht... c ngha l pH nh hng ti
pKa ca cc nhm ion chc nng ca Enzyme, cng nh c cht. Mi Enzyme c mt pH ti
u v d: Chymotrypsin l 8,0; Trypsin l 2,0 v.v
Tc dng d lp th (Allosteric): l mt trong nhng kiu tc dng iu chnh
Hnh 3.2. S v kiu tc dng d lp th. Khi gn mt phn t tn hiu vo mt v tr
trong Enzyme dn n s thay i cu trc ca n, t thay i hot tnh ca Enzyme
hot ca Enzyme. Mt s cht tc ng khng trc tip vo trung tm hot ng m vo
mt v tr no ca Enzyme lm cho cu trc bc III ca n thay i cht t, t hot
ca Enzyme thay i, n c tnh cht iu chnh hot ca Enzyme, in hnh kiu tc ng
ny l cch tc ng ca cc hormone (hnh 3.2).
4. Cht phi hp ca Enzyme (cofactor).
Nhiu Enzyme trong qu trnh xc tc li i hi phi c s phi hp ca mt cht hu
c gi l coEnzyme hay nhm ph, nhiu trng hp i hi phi c kim loi tham gia vo c
ch xc tc. Nhng cht hu c c hiu v cc ion kim loi c vai tr nh vy c gi l
cht phi hp hay cht cng tc (Cofactor). Cc cht cng tc khi kt hp vo phn t
Enzyme b sung kh nng phn ng v kh nng xc tc cho phn t Enzyme. Thiu cc
cht ny thng Enzyme khng hot ng c. Cc cht hu c c th gn cht vo phn t
Enzyme hoc cng c th ch kt hp lng lo, xu th hin nay mun gi chung l coEnzyme.
CoEnzyme thng hot ng vi s lng rt nh so vi c cht v thng sau mi
phn ng c th tr li trng thi ban u tip tc tham gia phn ng. Nh vy coEnzyme
thc s tham gia vo c ch xc tc. Tuy nhin, mt s coEnzyme tham gia phn ng ging
nh nhng cht tham gia phn ng khc, cho nn theo quan nim ng hc cng nh v c
cht, nhng coEnzyme ny c th c coi l nhng c cht thng thng. Nhng nu
coEnzyme no gn cht vo Enzyme bng lin kt ng ho tr th hin nhin n ch ng
vai tr trong c ch xc tc m thi.
S lng coEnzyme tng i t, mt coEnzyme c th phi hp vi nhiu loi
Enzyme, v d NAD
+
, NADP
+
c th phi hp vi nhiu Enzyme kh hydro
(Dehydrogenase). Nhiu cht chuyn ho trung gian cng mang nhng c tnh ca
coEnzyme nh acid Ascorbic, glucose 1-6-diphosphate.v.v.
V cu trc ho hc, nhiu coEnzyme c cu trc ca mt nucleotide n hoc i hoc
mt phn cu to ca n l nucleotide, mt s coEnzyme l nhng nhm Hem. CoEnzyme c
lin h cht ch vi cc vitamin (bng 3.1). C th ng vt bc cao c kh nng tng hp cc
coEnzyme t cc vitamin. Nhng coEnzyme thng gp l nhng cht cng tc ca nhng
Enzyme oxy ho kh v nhng Enzyme vn chuyn nhm.
Cc coEnzyme oxy ho kh gm 5 nhm l: Nicotinamide, Flavin, Quinone,
Metaloporphyrin v nhm Protein st. Cc nhm ny khc nhau v th nng oxy ho kh, v
s in t c vn chuyn trong qu trnh chuyn t dng kh sang dng oxy ho. Ba nhm
u trao i ion Hydro v in t, cc phn ng do chng xc tc u thuc loi vn chuyn
Hydro. Hai nhm sau ch trao i in t v cc phn ng do chng xc tc thuc nhiu loi
khc nhau. Th nng oxy ho kh ca loi ny thay i rt nhiu, tu thuc vo cc phn t
protein m cht cng tc gn vo.
Cc coEnzyme vn chuyn nhm chia thnh hai nhm chnh:
Nhm mt bao gm CoEnzyme A, acid Lipoic v S-adenosyl-methionine. Phn hot
ng chnh ca cc phn t nhm ny l mt nguyn t lu hunh, nguyn t ny c kh
nng cha 10 in t lp ngoi cng, c vai tr nh ci ti ht in t, do lm tng kh
nng ion ho nguyn t Carbon lin kt vi n.
Nhm th hai gm Biotin, Thiamine pyrophosphate, Pyridoxal phosphate v acid Folic.
Tc dng ca nhng cht ny ch yu l nh mt h thng lin hp bao gm mt d nguyn
t. Vi tc dng ca d nguyn t, b phn ca coEnzyme c ion ho thnh anion. S ion
ho ny to ra giai on m u qu trnh phn ng.
Chng ta hy xem xt mt s CoEnzyme sau y:
Bng 3.1. Mi lin quan ca mt s vitamin vi CoEnzyme
CoEnzyme nicotinamide.
Trong loi ny thng gp 2 cht chnh l Nicotinamide Adenine Dinucleotid (NAD
+
)
v Nicotinamide Adenine Dinucleotide phosphate (NADP
+
). Hai coEnzyme ny c trong tt
c mi t bo. NAD
+
thng nhiu hn NADP
+
khong 10 ln.
Hai coEnzyme ny tham gia vo nhng phn ng oxy ho kh do cc Dehydrogenase
xc tc. Cc Enzyme ny rt c hiu vi NAD
+
hoc NADP
+
. Mt s Enzyme c th hot
ng vi c hai coEnzyme nhng mc c hiu vi tng coEnzyme th khc nhau. NAD
+
thng tham gia cc phn ng oxy ho kh cung cp nng lng cho c th. Cn NADP
+
thng tham gia vo cc phn ng sinh tng hp.
Cc phn ng c s tham gia ca cc coEnzyme ny thng l nhng phn ng lin
quan ti lin kt i gia carbon v oxy, gia carbon v nit v trong mt s trng hp l
gia carbon v carbon.
C ch hot ng ca hai coEnzyme ny ging nhau: Trong qu trnh oxy ho kh,
nhn niconamide trc tip tham gia phn ng, carbon v tr th 4 c kh nng nhng hoc
nhn mt nguyn t Hydro, phn cn li ca coEnzyme l kt hp vo Enzyme. Trong
phn ng ny, mt nguyn t hydro ca c cht gn ln nhn nicotinamide, cn mt
nguyn t hydro khc xut hin trong mi trng di dng proton v in t ca n kt
hp vo nhn nicotinamide v trung ho in tch dng ny (hnh 3.3).
CoEnzyme flavin.
Hnh 3.3. Cu to phn t v c ch hot ng ca coEnzyme Nicotinamide
Hnh 3.4. Cu to phn t ca FAD v c ch hot ng ca coEnzyme Flavin
Loi ny thng gp hai cht quen thuc l Flavin mononucleotide (FMN) v Flavin
Adenine Dinucleotide (FAD). Cc Enzyme kt hp vi coEnzyme flavin di tn chung l
flavoprotein. Ngoi tc dng vo lin kt gia carbon vi mt d nguyn t nh S, O, N
cc Enzyme flavoprotein cn tc dng vo nhiu loi lin kt khc.
C ch tc dng: Cc phn ng kh xy ra qua hai bc: Bc th nht mt nguyn
t hydro c gn ln N
1
ca flavin v lm gim i mt lin kt i, nhn ny mang mt in
t c thn N
5
, in t ny c gi n nh l do c tnh cng hng cao ca nhn ; Bc
2 mt nguyn t hydro na c kt hp vo N
5
v to nn coEnzyme dng kh (hnh 3.4).
CoEnzyme quinone.
CoEnzyme ny c gi l coEnzyme Q hay Ubiquinone. Trn thc t c hng lot
coEnzyme quinone u l dn xut ca benzo-quinone v u c mt lin kt nhnh di gm
nhiu gc terpen. Lin kt nhnh ny ca mi cht khc nhau (s n terpen khc nhau).
CoEnzyme Q loi ng vt c v thng c lin kt nhnh di ti 10 gc terpen gi
l coEnzyme Q
10
(n=10). Tt c nhng cht ny l nhng coEnzyme oxy ho kh. Cc cht
ny tham gia vo qu trnh oxy ho kh gia nhng Dehydrogenase v Cytocrom b trong
chui h hp t bo ca ty th. Vitamin K v E c xp vo loi cht ny (hnh 3.5).
Hnh 3.5. Cu to phn t v c ch hot ng ca coEnzyme Quinone
CoEnzyme hem.
Nhiu Enzyme cn s cng tc ca nhm Hem. v d: H thng Cytochrome, Catalase,
Peroxidase. Vai tr ch yu ca cc coEnzyme ny l vn chuyn in t nh kh nng bin
i thun nghch ca st gia trng thi Fe
2+
v Fe
3+.

Dng kh Dng Oxy ho.
CoEnzyme A (CoASH).
Hnh 3.6. Cu trc phn t CoEnzyme A.
Cu to ca coEnzyme ny gm c mt gc 3
,5
diphosphoadenosine lin kt vi mt
phn t 4- phosphopantethein. Phn pantethein c nhm thiol (-SH) hotng. CoEnzyme
ny vn chuyn nhm acyl (gc acid) v tham gia vo phn ln cc phn ng ngng t vi
cc phn t acetate hoc acid bo khc to ra nhng chui carbon di hn. Trong phn ng
ny acid bo phi c gn vo coEnzyme A qua lin kt thioester gia nhm carbonyl ca
acid bo v nhm thiol ca coEnzyme A. Trong dn cht ng ho tr ny, do tc dng ca
nguyn t lu hunh, cc in t c phn b li v do cc nguyn t bn cnh d dng
ion ho v to cho gc acyl mt hot tnh mi, ngha l gc acyl c hot ho. S hot ho
ny c th xy ra nhm carbonyl (hot ho u) hoc nhm methyl cui cng ca gc acyl
(hot ho ui) (hnh 3.6).
S- Adenosine methionine.
Methyl ho l mt phn ng rt quan trng v methionine l cht cung cp nhm
methyl quan trng nht.
Nhm methyl trong methionine c kt hp bng lin kt thioester c th nng vn
chuyn rt thp, v vy qu trnh vn chuyn nhm methyl phi qua mt giai on hot ho
trung gian bng cch gn mt phn t adenosine (ca ATP) vo nhm methionine. Trong
dng kt hp ny, nguyn t lu hunh ca methionine tr thnh ion sulfonium c tc dng
hot ho nhm methyl, chun b cho phn ng vn chuyn nhm methyl n cht tip nhn
(hnh3.7).
Hnh 3.7. Cu trc phn t S-Adenosine methionine
CoEnzyme lipoic (acid lipoic)
ht ny tham gia vo phn ng kh hydro ca acid pyruvic v mt s t phn ng cng loi.
lipoic c gn cht vo phn t Enzyme bng lin kt amide gia nhm carboxyl ca n v
nhm amin tn cng ca lysine (ca Enzyme). Phn hot ng ca coEnzyme ny l mt lin
kt disulfide (S-S). Lin kt ny c th m ra hoc kt hp vi cc phn t ca mt phn t
cht hu c, mt nguyn t lu hunh lin kt vi hydro v nguyn t lu hunh th hai lin
kt vi carbon. Trong phc hp multiEnzyme ca qu trnh kh carboxyl oxy ho acid
pyruvic, coEnzyme ny c vai tr phi hp cht ch vi coEnzyme Thiamine pyrophosphate
Hnh 3.8. Acid lipoic v c ch hot ng phi hp vi TTP
(TPP), nhm aldehyde (c to thnh sau khi tch CO
2
khi acid pyruvic) c chuyn t
TPP n coEnzyme lipoic, mt nguyn t lu hunh mang hydro v mt nguyn t lu hunh
th hai mang nhm acetyl. Nh vy acid lipoic va l coEnzyme vn chuyn nhm va l
coEnzyme oxy ho kh, n hot ng nh mt cnh tay di ng ca phc hp a Enzyme
(hnh 3.8).
CoEnzyme thiamine pyrophosphate.
Thiamine pyrophosphate ng vai tr coEnzyme trong mt lot cc phn ng phn ct
lin kt carbon carbon st nhm carbonyl, ni chung l ca acid cetonic. V tr xc tc
ch yu ca coEnzyme ny l carbon th hai ca nhn thiazol. Carbon v tr ny c khu
tr gia nguyn t S v nguyn t N c lin kt i v mang in tch dng, nn rt d ion
ho thnh carbanion i nhn (hnh 3.9).
CoEnzyme pyridoxal phosphate.
CoEnzyme ny l dn cht phosphoryl ho ca vitamin B
6
, thnh phn cu to c nhn
pyridin mang nhm aldehyde v tr para. Nhm ny l b phn trc tip hot ng ca
coEnzyme. Tu theo tng iu kin c th, coEnzyme ny tham gia vo cc phn ng vn
chuyn nhm amin, phn ng kh carboxyl hay phn ng ct gc R ca acid amin (hnh
3.10).
Hnh 3.9. Cu trc phn t CoEnzyme Thiamine Pyrophphate
CoEnzyme biotin.
CoEnzyme ny gm c mt nhn d vng Tetrahydrothiophen gn lin vi mt gc
ureido v mt lin kt bn l acid valeric. Biotin thng c kt hp vo apoEnzyme bng
lin kt amide gia nhm carboxyl ca n v nhm NH
2
ca lysine (ca apoEnzyme). Lin
kt bn ca coEnzyme cng vi lysine ca apoEnzyme to nn mt lin kt thng di 14A
0
di
ng rt d dng trong qa trnh xc tc.
Biotin l coEnzyme tham gia vo cc phn ng vn chuyn nhm carboxyl, qu trnh
ny gm hai bc: Bc 1- nhm CO
2
c gn vo N
1
ca biotin to nn carboxybiotin.
Bc 2 biotin chuyn nhm carboxyl n mt c cht khc v c cht ny c carboxyl
ho (hnh 3.11).
Hnh 3.10. Cu trc phn t v c ch hot ng ca coEnzyme pyridoxalphosphate.
Cc Enzyme cng tc vi biotin c th chia lm 3 nhm: Carboxylase, Decarboxylase,
Transcarboxylase.
Trong hnh 3.11 ta c:
(a) Cu trc phn t ca coEnzyme biotin.
(b) C ch hot ng.
R= H ---------> Biotin
R= -COO
-
-------> N-Carboxybiotin
Hnh 3.11. CoEnzyme Biotin.
5. c im hot tnh ca Enzyme.
Enzyme cng ging cc cht xc tc ho hc khc l lm tng tc phn ng, khng
mt i, khng tng ln trong qu trnh phn ng, n gip cho phn ng nhanh chng t ti
trng thi cn bng ng, n khng quyt nh chiu hng ca phn ng, nhng do trong c
th cc sn phm ca phn ng ny li l c cht ca phn ng tip theo nn phn ng hu
nh i theo mt chiu. Tuy nhin Enzyme c c im khc vi cc cht xc tc khc l:
So vi cc cht xc tc ho hc th Enzyme l cht xc tc c hiu xut cao nht (1,6 g
Amylase trong 1 gi thu phn c 175kg tinh bt).
Enzyme hot ng vi tnh c hiu ht sc cao, thng mi Enzyme ch xc tc cho
mt loi phn ng hay mt c cht ti hng ng phn quang hc.
Enzyme l cht xc tc c kh nng gia tng tc xc tc ti 10
6
10
7
ln vi c
hiu rt cao. S d c c tnh c hiu ny l do c s kt hp n khp v mt cu trc gia
Enzyme vi c cht (th hin bi cc gc, cc nhm ho hc).
Enzyme hot ng trong iu kin sinh l bnh thng, ng vt mu nng l nhit
ca c th, pH ca m bo, p sut kh quyn v mi trng nc.
6. Tn gi v phn loi
6.1. Tn gi
Enzyme c gi theo qui tc sau: Tn la tinh ca phn ng hoc c cht m Enzyme
tc dng + ui ase (aza). V d: Enzyme phn gii lipid c tn l lipase; phn gii tinh bt
(amylum) c tn l Amylase; Enzyme thc hin qu trnh oxy ho c tn l oxydase, bn cnh
vn c cc tn c gi theo thi quen lch s nh Enzyme pepsin, trypsin... y l cc
Enzyme protease.
6.2. Phn loi
V phn loi, Enzyme c chia lm 6 lp ln (bng 3.1) l:
Lp I: Enzyme oxy ho kh (oxydoreductase): thc hin cc phn ng oxy ho kh
hoc c lin quan.
Lp II: Enzyme vn chuyn (trans pherase): thc hin vn chuyn cc cht hoc cc
nhm ho hc.
Lp III: Enzyme thu phn (hydratase): thc hin cc phn ng thu phn hoc tng
hp c lin quan n nc.
Lp IV: Enzyme ng phn ho (isomerase, mutase): thc hin cc phn ng chuyn
dng ng phn ny sang dng ng phn khc.
Lp V: Enzyme liase: thc hin cc phn ng phn gii hoc tng hp nn cc lin kt
i.
Lp VI: Enzyme ligase (kinase, syntetase): thc hin cc phn ng phn gii hoc tng
hp nn cc cht c lin quan n nng lng ca ATP.
Bng 3.1. Phn loi Enzyme
S th t Lp Enzyme Phn ng xc tc
1. Oxidoreductase Chuyn (ion hydride: H hoc nguyn t H)
A + B A+B
2. Transferase Phn ng chuyn nhm A B +C A+B - C
3. Hydratase Phn ng thu phn - chuyn nhm chc cho phn t
nc
A-B+H
2
O A-H+B-OH
4. Isomerase Chuyn nhm chc trong phn t to cc dng ng
phn
X Y Y X

A- B A -B
5. Lyase Phn ng chuyn ho nh b sung nhm chc vo lin
kt i hoc to lin kt i nh ly i nhm chc
X Y

A- B A = B+X-Y
6. Ligase Tng hp hoc phn gii lin kt C- C, C-S, C-O v C-
N c lin quan n nng lng ca ATP
7. C ch xc tc ca Enzyme
7.1. Nguyn l v c ch xc tc ca Enzyme
Tnh xc tc sinh hc ca Enzyme th hin chnh ch vi mt nng rt nh
Enzyme cng c kh nng lm tng tc phn ng ln hng ngn vn ln. Cng nh cc
cht xc tc khc Enzyme khng tham gia vo sn phm cui cng ca phn ng, n ch lm
cho phn ng nhanh chng t ti trng thi cn bng ng. hiu c c ch xc tc ca
Enzyme cn nh li mt s iu kin nhit ho ng hc phn ng tin hnh. Tc phn
ng ho hc ph thuc vo nhiu yu t, l:
S va chm nhau ca cc cht tham gia phn ng nht l cc va chm hu hiu, kh
nng va chm ny ph thuc vo nng ca chng v s nhiu ng mnh (tc l ni nng
ca chng).
Nng lng hot ho ca cht tham gia phn ng: tc phn ng ho hc ni chung
c xc nh bi gi tr nng lng hot ho, tc l mc nng lng cc cht tham gia phn
ng phi t c, ct t cc lin kt cn thit v hnh thnh cc lin kt mi. Nng lng
hot ho cng ln th tc phn ng cng chm v ngc li, nng lng ny cng thp th
tc phn ng cng tng. Mun t ti nng lng hot ho th cn np cho phn t cht
mt ngun nng lng t bn ngoi di dng nhit nng, quang nng hoc in nng...
Cht xc tc (Enzyme) c tc dng thc y tc phn ng ho hc, v lm gim nng
lng hot ho phn ng.
Enzyme ch nh hng ln tc phn ng, khng nh hng ti cn bng phn ng.
Mt phn ng c xc tc bi Enzyme thng theo trnh t sau:
Trong : E = Enzyme; p = Sn phm phn ng (Product), ES v EP = Phc Enzyme
vi c cht v sn phm.
Bt k phn ng bin i S P no cng c th din t theo s thay i nng lng
phn ng m trong cc h sinh hc n thng c din t theo s thay i nng lng t do
G. Chng ta cng bit bt k cht no S hay P u c nng lng t do nn v ngi ta s
dng i lng G0 biu th s thay i nng lng t do chun m t thay i nng
lng t do ca phn ng iu kin chun tng ng vi nhit 298 K, p sut 1 atm
hoc 101,3 Kpa, nng c cht l 1M. Do phn ng sinh hc thng din ra vi cc cht c
nng nh hn rt nhiu so vi 1M v pH 7,0 nn thay v G0 bng G0, biu th s
thay i nng lng t do pH 7,0 tnh ton ng hc ca cc qu trnh bin i sinh hc.
S cn bng gia S v P phn nh s khc bit trng thi nn ca chng. Trng hp P
c trng thi nn t do thp hn S ngha l G0 ca phn ng l m (-) v cn bng phn
ng c xu hng v pha to P. S cn bng c li hng v pha to P khng c ngha l qu
trnh bin i S thnh P d dng xy ra v tc phn ng cn ph thuc vo cc thng s
khc na. Gia c cht tham gia phn ng v sn phm to ra tn ti hng ro cn nng lng
gi l trng thi chuyn tip. Trng thi ny khng biu th sn phm trung gian no, m ch
biu th thi im xy ra s bin i c bn bin S thnh P.
chnh lch gia trng thi nn v trng thi chuyn tip gi l nng lng hot ho
G. Trong Guncat biu th nng lng hot ho ca phn ng khng c xc tc (hnh
3.12). Nng lng hot ho cng cao tc phn ng cng thp v ngc li. Do , tc
phn ng gia tng khi nhit , p sut v nng cht tham gia phn ng gia tng. V cc
yu t ny lm tng chuyn ng hn lon ca cc cht tham gia phn ng v s lng cc
phn t c kch thch vt qua ro cn nng lng ng ngha vi s gia tng tc phn
ng. Mt khc, c th gia tng tc phn ng bng cch b sung cht xc tc lm gim mc
nng lng hot ho.

G
cat
Nng lng hot ho c xc tc.
G
Nng lng hot ho khng xc tc.

Hnh 3.12. So snh to ca phn ng bin i S
Do vy, trong nhng trng thi trung gian trn, trng thi no c mc nng lng hot
ho cao nht, th n s l bc gii hn tc ca phn ng.
7.2. Xc nh tc v cn bng phn ng.
Theo nhit ng hc, cn bng phn ng lin quan cht ch vi G0, cn tc phn
ng th lin quan ti G.
Trong qu trnh bin i S P, cn bng phn ng c xc nh bi hng s cn bng
Keq ; iu kin chun Keq s l Keq = [p] / [s] (3. 2)
Keq quan h vi G0 bng phng trnh:
G0 = - RT ln Keq (3.3)
Trong R = hng s kh (8,315 J/mol. K)
T = nhit tuyt i iu kin chun (298K)
Keq phn nh bin i nng lng t do chun, trong G0cng (-) th phn ng
cng d xy ra, nhng khng c ngha l G0cng m th tc phn ng cng ln.
Tc phn ng ph thuc vo nng cc cht tham gia phn ng v hng s tc
K. Nh vy, tc phn ng trong mt n v thi gian.
V = K[S] (3.4)
Theo (3.4) th V ch ph thuc vo nng ca 2 c cht th phn ng c gi l bc 2
vi:
V=K[S1] [S2] (3.5)
7.3. C ch xc tc ca Enzyme.
V c ch xc tc ca Enzyme c nhiu gi thit nhng u thng nht ch l qu
trnh xc tc bt u bng s kt hp gia Enzyme vi c cht to thnh phc hp trung
gian, c cht kt hp vi Enzyme phn trung tm hot ng, hin tng chn lc c hiu
c thc hin giai on ny. C cc thuyt gii thch c ch hot ng ca Enzyme nh
sau:
7.3.1. Thuyt hp cht trung gian: do Nensky xng v Langhenbec pht trin,
thuyt ny gii thch trng hp Enzyme v c cht l ng pha. Theo thuyt ny Enzyme to
vi c cht thnh nhng hp cht trung gian khng bn vng nh sn phm to ra vi mc
i hi nng lng hot ho thp hn bnh thng, ta c th hnh dung nh sau:
Gi s c phn ng: A + B AB tin hnh chm. Khi c Enzyme K th qu
trnh din ra nh sau: A + K AK vi mc nng lng thp.
AK + B AB + K cng vi mc nng lng thp.
Tm li l: A + B + K AK + B AB + K
Tc phn ng tng v n i theo con ng vng trnh mc nng lng hot ho
cao. Bng cch o mc nng lng hot ho, ngi ta cng thy c iu : V d: phn
ng phn gii H
2
O
2
H
2
O + O
2
c mc nng lng hot ho l 18 kcal/mol. Khi c
peroxydase th mc nng lng hot ho ch cn 2 kcal/mol. Bng quang ph hp ph cho
thy c s tn ti ca hp cht trung gian. Bnh thng quang ph hp ph ca peroxydase l
4 vch, khi cho tc dng vi H
2
O
2
n mt i 2 vch, khi H
2
O
2
phn gii ht n li c 4 vch
nh c. iu chng t c s tn ti ca hp cht trung gian peroxydase - H
2
O
2
. Nhng
nghin cu v trung tm hot ng ca Enzyme cng em li nhiu dn chng v hp cht
trung gian gia Enzyme vi c cht. S hp cht trung gian c trnh by hnh 3.13.
C cht Hp cht trung gian Sn phm Enzyme
Hnh 3.13. S hp cht trung gian
7.3.2. Thuyt hp ph: do Bailix xng (1906) sau c nhiu tc gi b xung.
Thuyt ny gii thch hin tng Enzyme vi c cht l khc pha. Nh trng thi phn tn cao
m din tch hp ph ca Enzyme l rt ln, lm ch thu ht c cht, c cht tp trung li lm
cho nng tng cao, cc va chm hu hiu tng, nn tc phn ng tng. Qu trnh hp
ph ny khng ch tun theo cc quy lut vt l n thun m n b chi phi bi cc yu t
ho hc phc tp dn n hin tng hp ph c chn lc gia Enzyme v c cht, ngoi ra
hin tng d tin hnh phn ng trn b mt Enzyme cn c ct ngha bng nhng bin
i trong nhng cu trc ca cc lin kt nguyn t c cht di nh hng ca lc trng
ca cc tng tc phn cc in... m phn t Enzyme em li, cho nn chng d phn ho
hoc lin kt vi nhau. Nh vy hp ph y cng c tnh chn lc, ch ng v rt c th
v nhng nh hng m mc nng lng hot ho c h thp to iu kin cho phn ng
d thc hin.
7.3.3. C ch xc tc acid base. Trong cc phn ng ho sinh lun c s hnh thnh
cc cht trung gian mang in th khng bn, d dng b phn r tr li trng thi ban u.
Tuy nhin, chng c th c n nh nh s trao i proton vi s tham gia ca H+, H
3
O+,
OH- trong mi trng nc. Trng hp ny gi l xc tc acid base, chng xy ra trong
mi trng phn ng ngoi nc cn c cc cht cho v nhn proton khc. Mt s acid amin
tham gia trung tm xc tc Enzyme nh Glu, Asp, Lys, Arg, Cys, His v Tyr ng vai tr lm
cht cho ( dng acid) hoc cht nhn proton ( dng Base) (hnh 3.14).
7.3.4. Xc tc thng qua to lin kt ho tr tm thi.
Cc lin kt ny tn ti trong khong thi gian rt ngn gia c cht v Enzyme, n
hot ho phn ng rt mnh. Nhiu gc acid amin v cofactor ca Enzyme ng vai tr l
nhm a nhn.
7.3.5. Xc tc thng qua ion kim loi. Cc Enzyme c cha kim loi th kim loi gip
nh hng c cht vo tm phn ng hoc gip n nh trng thi chuyn tip. Ngoi ra, kim
loi cn tham gia phn ng oxy ho kh. C ti 1/3 s Enzyme cn s tr gip ca ion kim
loi th hin hot tnh sinh hc ca mnh.
8. ng hc Enzyme.
8.1. Phng trnh ng hc Michaelis Menten.
Nm 1913, Michaelis v Menten a ra m hnh ng hc gii thch phn ng c
xc tc bi Enzyme v lp phng trnh phn nh quan h gia vn tc phn ng v nng
c cht S v Enzyme. im quan trng nht ca m hnh ny l trc khi phn ng xc tc
xy ra gia E v S c s to phc ES. Phc ny tip tc bin i to ra sn phm phn ng v
gii phng Enzyme tip tc chu trnh phn ng xc tc mi.
E + S E S P + S
k
3 k
1
k
2
( 3 . 6 )
Hnh 3.14. C ch
xc tc acid base.
K
1
, K
2
, K
3
l hng s tc ca cc vn tc phn ng tng ng V1, V2,V3. y K4
l hng s tc trong phn ng to phc ES t P v E l rt khng ng k nn c th b
qua. Do vn tc chuyn ho phc ES thnh P v E l:
V
0
= K3 [ES] (3.7)
s quyt nh mc phn ng chuyn ho S P. Trong thc t, vn tc ny ph
thuc vo nng ES. Nng ES cng cao th vn tc phn ng cng ln. Gi s k hiu:
[E0] = nng Enzyme ban u
[ES] = nng Enzyme- c cht
[E] = nng Enzyme t do khi t im cn bng.
Ta c: [E] = [E0] [ES]
Coi [S] l nng c cht ban u v cng c xem l nng c cht trong
trng thi cn bng ca phn ng. V trong thc t, nng c cht lun lun gp nhiu ln
Enzyme. Hn na, trong nghin cu ng hc ngi ta thng ch quan tm xc nh tc
phn ng ban u, khi lng c cht b chuyn ho cha ng k so vi nng ban u.
T (3.6) ta c:
a/ - Vn tc phn ng to phc ES l: K1 ([E0] [ES]) [S]
b/ - Vn tc phn ly phc ES l tng ca 2 phn ng.
ES phn ly thnh E v S vi hng s tc K2 v ES phn ly thnh E v P vi hng s
tc K3. Do vn tc phn ly phc ES l (K2 + K3) [ES]. Khi h thng t cn bng ta
c:
K1([E0] [ES]) [S] = (K2 +K3) [ES] (3.8)
T ta c: [ES] = K1 [E0] [S]/ K1 [S] + (K 2+ K 3)
Chia hai v phi cho K1 v d tnh ton ta thay K2+K 3 / K1 bng hng s Michaelis
Menten Km, ta c:
[ES] = [E0 ] [S] /Km + [S] (3.9)
Thay [ES] vo (3.7) ta c:
V0 = K 3[E0] [S] /Km + [S] (3.10)
Khi nng c cht ln tt c cc phn t Enzyme tham gia phn ng u to
phc vi S, lc y ta c:
[ES] = [E0] v theo l thuyt, khi phn ng s t vn tc cc i Vmax = K3[Eo]
Hnh 3.15. nh hng nng c cht i vi tc xc tc ban u.
T ta c: Vo = Vmax [S] /Km +[S] (3.11).
Phng trnh (3.11) c gi l phng trnh Michaelis Menten phn ng tng quan
nh hng gia tc ban u ca ph ng Vo, tc ti a Vmax, nng c cht ban u
[S] v hng s Km. Theo phng trnh trn, khi Vo = 1/2 Vmax th:
Vmax/2 = Vmax[S] /Km + [S] (3.12)
Chia 2 v cho Vmax ta c:
1/2 = [S]/ km + [S]. T ta c:
Km + [S] = 2[S]
Km = [S] khi V0 = 1/2 Vmax
Da vo phng trnh ny ngi ta dng c th hyperbol phn nh nh hng
nng c cht n vn tc ban u ca phn ng (hnh 3.15).
8.2. ngha ca Vmax v Km.
Theo suy lun: Hng s Km c gi tr tnh theo mol bng nng tnh theo mol ca c
cht thi im tc phn ng ban u do Enzyme xc tc Vo bng 1/2 Km. d dng
xc nh Km v Vmax ngi ta ly nghch o c hai v phng trnh Mchaelis- Menten:
1/V0 = Km +[S]/Vmax [S]
tch v phi v n gin tip s c phng trnh Lineweaver Burk
1/Vo = Km/Vmax 1/[S] +1/Vmax.
y l phng trnh tuyn tnh c dng ( y= ax +b ) vi th l ng thng ct trc
tung 1/Vmax, ct trc honh (-1/Km) v c nghing bng (km/Vmax). Phng trnh
ny cho php d dng xc nh gi tr Vmax v Km trong mt vi th nghim xc nh tc
Vo ca phn ng do Enzyme xc tc vi 1 s nng c cht ban u (hnh 3.16).
Hnh 3.16. Bin i Lineveaver-Burk.
Trong cc phn ng Enzyme nhiu bc, phn ln Enzyme dng EP, cho thun tin
ngi ta gi hng s gii hn tc phn ng l Kcat. Ngoi ra, biu th hot xc tc
ngi ta thng s dng khi nim s chu trnh quay ca Enzyme c k hiu l Kcat/ s
phn nh s phn t c cht bin i thnh sn phm P trong mt n v thi gian bi 1 phn
t Enzyme khi c bo ho bi c cht.
8.4. S c ch hot tnh Enzyme
C 2 nhm cht c ch Enzyme: c ch thun nghch v c ch khng thun nghch.
8.4.1. Nhm cht c ch thun nghch: Nhm ny c phn thnh 3 nhm ph:
c ch cnh tranh: Th hin s c ch bng cch cnh tranh trung tm xc tc Enzyme
vi c cht. Thng thng cc cht c ch cnh tranh c hnh dng ging c cht, do d
dng to phc EI (I = inhibidor) v ngn chn to phc ES.
V l c ch thun nghch nn c th hn ch nh hng ca cht cnh tranh bng cch
gia tng nng c cht.
c ch khng cnh tranh: Nhm ny c 2 nhm ph:
Nhm cht c ch khng cnh tranh: th hin c ch bng cch gn ln v tr gn tm
hot ng Enzyme nhng khng ngn cn c cht gn ln tm hot ng. Cht c ch khng
cnh tranh gn c ln Enzyme trng thi t do cng nh ln phc ES lm gim hot tnh
Enzyme, gim Vmax nhng hu nh khng nh hng i vi Km.
c ch bt cnh tranh: Cht c ch cng gn ln v tr nm gn tm hot ng
Enzyme, nhng ch gn khi phc ES c to thnh m khng gn ln Enzyme t do.
8.4.2. Nhm cht c ch khng thun nghch.
Nhm ny c ch Enzyme bng cch to lin kt ho tr vi Enzyme.
Trong nhm cht c ch khng thun nghch cn c mt s cht c ch kh c bit.
Bnh thng chng khng hot ng v ch bt u hot ng khi c gn ho tr vi tm
hot ng v lm mt hon ton hot tnh ca Enzyme. Cc cht c ch ny cn gi l cht c
ch t st.
9. Th d v phn ng xc tc Enzyme.
Ti nay ngi ta bit y hn 1.500 Enzyme khc nhau, trong mi Enzyme c
cu trc khng gian, c tnh v c ch xc tc ring bit. Tuy nhin, cc Enzyme ny thng
tp trung theo cc nhm c ch phn ng ging nhau v cng kh gn nhau v mt ngun gc
pht sinh v th t sp xp acid amin. Chng ta hy xt vi trng hp tiu biu sau y:
9.1. Enzyme protease Serine s dng Ser lm yu t xc tc hng nhn.
Trong nhm Enzyme ny c 3 Enzyme tiu biu l Trypsin, Elastase, v Chymotrypsin
-u l endopeptidase. Tuy xc tc phn gii cc lin kt peptide khc nhau: Trypsin ct lin
kt peptide nm cnh gc Lys, Arg. Chymotrypsin ct lin kt peptide nm cnh gc acid
amin nhn thm cn Elastase ct lin kt peptide nm cnh gc acid amin c kch thc nh
v khng phn cc.
Tuy nhin, chng u c trung tm hot ng cha His(57), Asp (102), Gly (103)v
Ser (195). C ch xc tc ca chymotrypsin ct lin kt peptide vi 6 giai on c trnh by
hnh di y (hnh 3.17):
1.To phc khi ng: Nguyn t O ca nhm carbonyl to lin kt hydrogen vi H
thuc nhm amide ca gc Gly(193) v Ser(195), cn Asp v His nm thng hng to lin kt
hydrogen vi nhm OH ca Ser(195).
2.To phc trung gian t din u tin: Ser (195) gii phng proton cho His (57) v tc
ng hng nhn vo nguyn t C ca nhm carbonyl c cht, lc ny His(57) ng vai tr
xc tc theo kiu acid base. S di chuyn In t (-) ca O thuc nhm carbonyl to ra phc
t din trung gian u tin gi l OXYANION l cht trung gian trng thi chuyn tip
khng n nh bi tng tc tnh in vi proton amide ca Ser(195) v Gly (193).
3.To phc Acyl-Enzyme trung gian v tch amin: Phc trung gian khng bn vng
c to thnh b phn r to ra phc trung gian bn vng hn, trong Ser(195) to lin kt
ester vi nhm COOH ca c cht v gii phng amin. C l His(57) ng vai tr tr gip
phn ng phn r.
4. To phc acyl- Enzyme trung gian vi 1 phn t nc.
5. Hnh thnh phc trung gian t din th 2.
6. To phc EP.
Ba bc phn ng sau lin quan ti qu trnh phn r phc acyl-Enzyme c hng
ngc li vi 3 bc u, ngoi tr phn t nc s thay th nhm NH
2
ca c cht.
9.2. Hexokinase xc tc phn ng vi 2 c cht:
Enzyme ny xc tc phn ng bin i Glucose v ATP thnh Glucose 6-phosphate v
ADP. N tn cng nguyn t P cui cng ca ATP nh nhm in (-) c mt trong trung tm
hot ng (B). Ngoi ra bn thn nhm P cui ca ATP lun c xu hng tch khi ATP.
iu ny cng lm cho qu trnh xc tc d dng xy ra hn (hnh 3.18)
10. Enzyme iu ho.
Enzyme iu ho thuc nhm Enzyme c bit c c ch hot ng khc vi a s cc
Enzyme bnh thng khc. Trong qu trnh trao i cht, cc chui phn ng ho hc c
xc tc bi cc Enzyme qua tng giai on theo th t nht nh gi l chu trnh. Trong mi
chu trnh phi c t nht 1 Enzyme iu chnh tc phn ng ca ton b chu trnh. Enzyme
ny gi l Enzyme iu ho. Thng trong cc chu trnh chuyn ho phn ng u tin c
xc tc bi Enzyme iu ho.
S d Enzyme iu ho c kh nng trn v hot tnh ca n c iu chnh bi nhm
cc cht iu ho c khi lng phn t nh (thng l bn thn cc cht trao i hoc cc
cofactor). Ta hy xem xt mt s c ch hot ng ca Enzyme iu ho.
10.1. Enzyme d lp th (Allosteric Enzyme).
Enzyme ny thay i hot tnh xc tc thng qua thay i cu hnh khng gian khi gn
vi cc cht iu ho c hiu ca n. C mt kiu iu ho rt ph bin i vi Enzyme d
lp th l iu ho c ch ngc (Feedback inhibidion). Bn cht ca n l Enzyme d lp th
xc tc phn ng u tin ca chui phn ng chuyn ho thng b c ch ngc bi chnh
sn phm ca chui phn ng.
Enzyme d lp th thng c nhiu tm iu ho. Do vy, n khc vi Enzyme bnh
thng ch: Enzyme d lp th ngoi tm hot ng gn c cht cn c mt hoc nhiu
tm iu ho gn cc yu t iu ho v cofactor. Cc tm gn ny nm cc v tr v
thm ch cc tiu n v khc nhau ca Enzyme, do vy Enzyme d lp th thng c kch
thc ln hn v cu trc khng gian phc tp hn.
Hnh 3.18. Phn
ng xc tc bi
Hexokinase
10.2. Enzyme iu ho ci bin nh to lin kt ho tr thun nghch.
Trong c ch iu ho ny, hot ng Enzyme c iu chnh nh s ci bin lin kt
ho tr ca phn t Enzyme. in hnh nht l phn ng gn nhm phosphate, nhm Adenyl,
nhm Uridyl, ADP Ribosyl v nhm Methyl.
10.3. Cc c ch khc iu ho hot tnh xc tc Enzyme.
Ngoi 2 c ch iu ho xc tc rt ph bin trn, cn c t nht 2 c ch khc: Mt s
Enzyme c iu ho nh gn hoc tch nhng phn t protein c hiu hoc c hot ho
t phn t Enzyme tin cht nh ct bt mt hay mt s on peptide. Trong thc tin, rt
nhiu Enzyme protease c hot ho t tin cht ca chng l Zymogen. in hnh l s
hot ho Trypsin v Chymotrypsin, hot ho hormone peptide v qu trnh Protease tham gia
xc tc qu trnh ng mu.
YU CU CN NM
CHNG III : ENZYME
Khi nim , bn cht ca enzyme. Trung tm hot ng ca enzyme. c im
hot tnh ca enzyme. Cc yu t nh hng n hot tnh ca enzym. C ch xc tc
ca enzyme.
CHNG III: EN ZYME
Cu 1: Trung tm hot ng ca enzym? Nhng yu t nh hng n trung tm ny?
Cu 2: C ch nh hng n hot tnh ca enzym bi nhit v pH?
Cu 3: C ch xc tc theo thuyt hp cht trung gian ca enzym?
Cu 4: C ch xc tc theo thuyt hp ph ca enzym?
CHNG IV
HO SINH HORMONE
1. i cng v Hormone
1.1. nh ngha.
Hormone: Danh t ny ln u tin c a ra nm 1904 bi Wiliam Bayliss v
Ernest Starling m t tc dng ca Secretin mt cht c sn xut bi t trng, c tc
dng kch thch s bi tit ca tu (ting Hylp, Harman c ngha l kch thch). Vit Nam
gi l Ni tit t - ch ngun gc tit ca hormone (cc cht do tuyn ni tit tit ra) hay cn
gi l Kch thch t- ch chc nng kch thch ca hormone.
*V mt ho hc: hormone l mt nhm cc hp cht hu c c bn cht rt a dng:
c th l protein nh Somatotropin thu trc tuyn yn c 200 gc acid amin; l polipeptide
nh Insuline ca tuyn tu c 51 acid amin; oligopeptide nh Oxitosine ca thu sau tuyn
yn c 8 acid amin; l dn xut ca acid amin nh Adrenalin - hormone ca min tu thng
thn l dn xut ca Tyrosine; l dn xut ca nhm Steroid nh Corticco Steroid - hormone
min v thng thn hay cc hormone sinh dc v.v. v c th l dn xut ca cc acid bo
nh Prostaglandin ca tuyn tin lit c bn cht l dn xut ca acid bo khng no (bng
4.1).
*V mt sinh hc: Hormone l nhng hp cht hu c c sn xut vi mt lng rt
nh bi nhng t bo c bit ch yu cc tuyn ni tit, gi nhim v iu chnh cc qu
trnh trao i cht, lm cho cc qu trnh tin hnh vi mt cng v mt chiu hng
thch hp vi nhu cu sng ca c th trong tng giai on, tng thi im nht nh.
1.2. Cc cch truyn thng tin ca t bo.
Cn phn bit nhng t bo ni tit vi nhng t bo khc v nhng cht bi tit ca
nhng t bo ny
1.2.1. T bo ni tit: l nhng t bo sn xut v bi tit trc tip vo mu nhng
cht c hot tnh sinh hc c gi l Hormone. V d t bo ca tuyn ty tit ra Insuline.

Bng 4.1: Mt s hormone v chc phn ca n
Hormone Ngun gc Chc phn
Vasopressin Yn sau Ti hp thu nc
Cortison V thng thn Lc cu thn
Calcidonin Gip trng c ch s huy ng Ca
2+
t xng
PTH Cn gip Huy ng Ca
2+
t xng, bi xut PO
4
Insuline Tuyn tu (T bo ) H ng huyt
Adrenalin Tu thng thn Tng ng huyt
Glucagon Tuyn tu (t bo ) Tng ng huyt
Cortisol V thng thn(b) Tng ng huyt
STH Tuyn yn trc Tng ng huyt, pht trin xng
T
4
, T
3
Tuyn gip trng Kch thch chuyn ho
FSH Tuyn yn trc Pht trin tuyn sinh dc
LH Tuyn yn trc Bi xut ca tuyn sinh dc
Estradiol Bung trng C quan sinh dc n
Progesteron Bung trng Lm
Testosteron Tinh hon C quan sinh dc nam
Prolactin Tuyn yn trc To sa
Hnh 4.1. S cc t bo ni tit, cn tit v t tit
Hnh 4.1. S cc t bo ni tit, cn tit v t tit
Prostaglandin Trong hu ht cc m Nhiu tc dng
Oxidoxin Yn sau Tng co bp c trn ca t cung v tuyn
v.
1.2.2. T bo thn kinh: Tit nhng hormone thn kinh (Neurohorrmone). V d
Vasopressin c tit ra bi cc t bo thn kinh vng di i trc tip vo mu nh h
thng thn kinh tuyn yn.
1.2.3. T bo cn tit-bng tit (paracrine): Tit nhng cht c tc dng trc tip n
nhng t bo gn k hoc khu tr ngay trong c quan ni tit, khng cn vn chuyn bng
mu. l nhng hormone ti ch, v d Somatostatin ca tuyn tu (Hnh 4.1).
Cng cn lu rng nhng cht dn truyn thn kinh khng thuc nhm hormone theo
ng nh ngha c in.
Nhng cht k trn gm hormone, hormone thn kinh, hormone ti ch v cht dn
truyn thn kinh c gi l nhng cht truyn tin th nht hay cht truyn tin ngoi t bo
( phn bit vi nhng cht truyn tin th hai hay cht truyn tin trong t bo).
Hormone c a vo mu, nhanh chng ti cc c quan tip nhn. Hormone c th di
chuyn xa vi khong cch hng mt hoc nhiu hn trc khi tip cn t bo nhn. Cn cc
cht dn truyn thn kinh ch di chuyn mt khong cch ngn chng vi micromet qua
synap n t bo thn kinh lin k hoc t bo nhn.
D khc nhau v phng din gii phu, cht dn truyn thn kinh v hormone rt
ging nhau v c ch tc dng sinh hc, n to nn mt h thng Thn kinh ni tit.
1.3. Ngun gc ca hormone
Hormone c nhiu ngun gc khc nhau:
Do cc tuyn ni tit (khng c ng tit) sn phm thm qua mao qun vo mu c
vn chuyn n mt b phn khc trong c th (thng gi l m bo ch, t bo ch)
pht huy tc dng. Trong c th ng vt i a s cc hormone l do cc tuyn ni tit tit
ra.
Ngoi tit: (cht tit khng c a vo mu) v d gastrin do vng h v ca d dy
tit ra c vo d dy nho trn trong khi thc n ln vng thn v kch thch vng thn
v tit dch v.
Ngun gc t thc vt: thc vt c rt nhiu cht kch thch t nh cc kch t sinh
trng thc y qa trnh sinh trng ca cy: v d nh Ausin; Indolaxetic, Giberein v.v.
mt s ht, c v cy cn c cc kch t sinh dc c pht huy tc dng i vi c th ng
vt, chng thng xut hin vo ma xun gy kch thch sinh theo ma cho ng vt n
c v chim mung.
1.4. Vai tr sinh hc ca hormone v mi lin h gia thn kinh v th dch
C th v ngoi cnh l mt khi thng nht m ngoi cnh lun lun thay i nh thi
tit thc n, nh sng v.v. thch ng c vi nhng bin i c th phi iu chnh
bng cch:
Tit dch (h n gin)
Thn kinh (h phc tp)
Hormone (th dch) cng vi h thn kinh tham gia iu chnh cc qu trnh trao i vt
cht ca c th. Trao i vt cht ca c th cng nh ca t bo l mt qu trnh phc tp
gm rt nhiu phn ng lin quan cht ch vi nhau. Bnh thng trong mt t bo trong mt
thi im c hng trm phn ng xy ra. Nhng phn ng do enzyme xc tc, nhng
enzyme ch gip cho phn ng tin hnh nhanh v c trnh t. Xt v mt tng qut enzyme
khng c tc dng iu chnh. Tc dng iu chnh ny l do h thng chuyn ho gip cho
nhng lot phn ng do enzyme xc tc c tin hnh ng lc, ng phng hng, ng
cng m m bo cn thit. H thng chuyn ho l hormone.
ng vt n bo cha c h thn kinh th s iu tit ch yu l th dch v hot
ng ca c th chng cn n gin. Qua qu trnh tin ho, c th ng vt xut hin h
thn kinh p ng nhng hot ng phc tp hn ca c th. Nhng trong qu trnh tin
ho ng vt vn gi c hai h thng v hai h thng ny hot ng phi hp nhau, s lin h
Tn hiu bn ngoi
hoc bn trong
Thn kinh trung ng
Vng di i
Hormon gii phng(ng)
Tuyn yn
Hormon ca tuyn yn
(g)
Tuyn ch
Hormon cui cng
M bo ch
Hnh 4.3. S tng quan v mi lin h gia hormone gii phng vng di i, tuyn yn
vi cc tuyn ch
Chu trnh kim sot
ngc ngn
Chu trnh kim
sot ngc di
Chu trnh kim sot
ngc ngn
Hnh 4.2. S v mi lin h gia thn kinh v th dch
Thn kinh trung ng
Vng di i
Cc hormone gii phng

GH TRH CRH Dopamin PRF gnRH
GIH PIF gnRIF
GH TSH ACTH -LTH PRL TSH LH
Pht trin xng Gan T. gip V thng -Endorbin Tuyn v B. trng B.trng
chuyn ho T.hon T.hon
Glucid, protein
T
3,
T
4
Thch nghi Gim au To sa Pht trin Rng trng
Tng ng vi stress nang Th vng
Huyt
Kch thch To tinh Progesteron
to testotteron trng
thng qua b phn di i (hypothalamus). Cc tuyn ni tit c mi lin h cht ch vi
nhau qua s iu tit chung ca tuyn yn, tuyn yn li chu s iu tit ca thn kinh trung
ng qua b phn di i, hnh thnh nn h thng hypothalamo - hypophysealis (thn
kinh- th dch).
So vi h thn kinh th hormone c hnh thnh sm hn, n hot ng chm hn
nhng n bao qut n tt c cc t bo. C th coi hormone l nhng tn hiu ho hc c
a ti t bo hng hot ng ca enzyme trong t bo theo chiu hng ng vi nhu
cu sng ca c th. Cn h thn kinh c hnh thnh sau hn n hot ng nhanh, chnh
xc hn nhng n khng bao qut n tt c cc t bo. S tng hp hay gii phng mt
hormone no u c kim sot mt cch cht ch bao gm ba giai on ca s tng tc
nh sau:
Hypothalamus gi vai tr ch o iu ho hot ng ca cc tuyn ni tit trc ht
hypothalamus tit ra cc tc nhn c tc ng kch thch gi l yu t gii phng RF
(Releasing factor) hoc l cc tc nhn c tc dng c ch IF (inhiliding factor). Cc tc nhn
ny tc ng n thu trc ca tuyn yn kch thch tit hormone cp I. Sau hormone
cp I ny s tc ng n cc tuyn ni tit khc, iu khin chng tit ra hormone cp II. Cc
hormone cp II c nhim v p ng li nhng i hi ca c th, ng thi chng c th
ngn chn s tit RF, IF ca hypothalamus hay ngn chn s tit hormone cp I theo c ch
iu ho ngc (Megative feedback ) (hnh 4.2, 4.3).
Tuyn yn
2. Phn loi hormone
Cn c phn loi hormone da vo bn cht ho hc ca hormone. Bn cht ho hc
ca hormone cng quyt nh tnh cht v c ch tc dng ca hormone nh tnh ho tan
trong nc, tc dng ln mng, ln gen... Cn c vo hormone c th c phn thnh bn
nhm chnh sau.
2.1. Hormone peptide
y l nhng hormone c t 3 acid amin tr ln, gm nhng hormone ca cc tuyn
vng di i, tuyn yn, tuyn tu... S tng hp cc hormone peptide thng xy ra li
ni cht, khi tng hp thng di dng pro-hormone, v d pro-Insuline dng ny n
cha c hot tnh. pro-Insuline gm ba chui: chui A gm 21 acid amin, chui B gm 30
acid amin. Hai chui ny c ni vi nhau bi 2 cu ni dissulfid v gia chng l chui C
c 30 acid amin. Khi c nhu cu v Insuline n c enzyme peptidase ct b chui C to
thnh Insuline c hot tnh.
Chui B
Phe Val Asp Gly His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu
ARG
S S Gly
Phe
S S Phe
Tyr
Chui A Thr
Ile Val Glu Gln Cys Cys Ala Ser Val Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Pro
S S
Hnh 4.4. Cu trc ca Insuline
Cc hormone peptide tan trong nc v c lu thng trong mu di dng t do, thi
gian p ng ngn (vi giy cho tc dng vi s tng ng huyt ca glucagon hoc chng
li niu ca vasopressin).
Hormone peptide khng thm nhp vo trong t bo ch m tc dng ln b mt t bo
ch thng qua cht cm th c hiu ca chng trn mng t bo.
2.2. Hormone l dn xut ca cc acid amin
Nhng hormone thuc nhm ny c khi lng phn t thp v thng l nhng dn
xut ca Tyrosine, gm nhng hormone ca min tu thng thn nh Adrenalin, Nor
adrenalin y l nhng hormone tan trong nc v nhng hormone ca tuyn gip trng nh
Triiodotyronin T
3
, Tetraiodtyronin T
4
(Thyroxin), chng t tan trong nc. S tng hp cc
hormone ny thng n gin v nhanh hn so vi nhng hormone peptide.
Cc hormone ny c lu thng trong mu di dng t do nh Adrenalin, Nor
adrenalin hoc c vn chuyn di dng kt hp vi protein nh hormone tuyn gip c
cht vn chuyn l TBG (Thyroxin binding globulin) vn chuyn Thyroxin T
3
, T
4
.
Thi gian p ng ca cc hormone ny rt ngn thng vi giy nh Adrenalin, Nor
adrenalin
Cc hormone ny cng khng thm nhp vo trong t bo ch m tc dng ln b mt
t bo ch thng qua cht cm th c hiu ca chng trn mng t bo.
2.3. Hormone Steroid
Cc hormone Steroid bao gm nhng hormone ca min v thng thn, ca tuyn sinh
dc. Cc hormone Steroid c tng hp t cholesterol. Chng c c tnh khng tan trong
nc, ch ho tan trong lipid, chng c lu thng trong mu thng nh cc yu t vn
chuyn c hiu, v d:
CBG (Corticosteroid binding globulin) vn chuyn cortisol, corticosteron, progesteron.
SBG (Sex hormone binding globulin) vn chuyn i vi cc hormone sinh dc
estradiol v testosteron.
Mt lng nh hormone thuc nhm ny lu trong trong mu di dng t do. Khi n
t bo ch hormone c tch khi protein vn chuyn sang dng t do. N xm nhp vo
trong t bo ch v kt hp vi cht cm th c hiu ca n to thnh hp cht trung gian
n tc dng ln DNA nhn ca t bo. Thi gian p ng ca hormone Steroid kh lu so
vi cc hormone peptide v hormone l dn xut ca acid amin.
2.4. Hormone l dn xut ca cc acid bo
Cc hormone thuc nhm ny thng pht huy tc dng ti ch (t vn chuyn xa t ni
chng c tit ra m c tc dng vi nhng t bo gn ni n c tit). i din nh
hormone prostaglandin (hnh 4.5).
O
||
COO
-
OH
Hnh 4.5. Cu to ca prostaglandin
3. C ch tc dng ca hormone
3.1. Hai nguyn l c bn v tc dng ca hormone:
Nguyn l th nht: Hormone di chuyn trong mu n mi c quan, nhng mi loi
hormone ch tc ng ln mt s c quan (hay t bo) chuyn bit nht nh. S d nh vy v
mi hormone khi n t bo ch s c phn bit bi cht tip nhn hay cht cm th
(Receptor) c trng ring ca mnh. Cht tip nhn hormone t bo ch c bn cht l
nhng prrotein. Chng khu tr ngay trn mng t bo hoc c phn b trong t bo
cht. Nhng hormone tan trong nc nh cc hormone c bn cht l protein, oligopeptide,
dn xut ca acid amin nh Insuline, glucagon, Adrenalin v.v. th cc Receptor ca chng
nh v ngay trn mng t bo. i vi cc hormone c bn cht Steroid hay cc hormone ho
tan trong lipid th cc Receptor ca chng phn b trong t bo cht. Khi cc hormone ny
xm nhp vo trong t bo chng thng kt hp vi cht tip nhn (Receptor) to thnh phc
hp trung gian hormone-Receptor, t cc phc hp ny s gy ra nhiu tc ng khc nhau.
Nguyn l th hai: Vic gn hormone vo cht tip nhn c hiu ca n to nn phn
t thng tin ni bo m sau n lm kch thch hoc gim nh hot tnh ho sinh c trng
ca m bo ch. i vi cc hormone ho tan trong nc, thng tin ni bo thng l 3
/
, 5
/
-
AMP vng hoc l 3
/
, 5
/
- GMP vng (thng tin th 2). Cn i vi cc hormone ho tan trong
lipid cc phc hp hormone-Receptor l cc thng ni bo.
3.2. C ch tc dng ca hormone
Trong nghin cu v c ch tc dng ca hormone th Adrenalin l cht u tin c
nghin cu c kt qu v c ch tc dng ln t bo gan mc phn t, xut pht t cng
trnh ca E.W. Sutherland v cng tc nm 1950. Sutherland c gii Nobel Y hc nm
1971 v pht minh ra AMP vng.
c tnh tc dng ca hormone l vi nng rt thp picomol (10
-12
mol), micromol
(10
-6
mol) nhng s pht huy tc dng li rt ln.
Khi nim v h thng thng tin th hai .
Cc hormone t cc tuyn ni tit c tit vo mu, t mu c a ti t bo ch,
chng phi chn cc t bo ch tc ng. iu kin ca mt t bo ch l phi c cc
Receptor cho hormone ( mng t bo hay bo tng hoc nhn t bo).
i vi cc hormone ho tan trong nc ( peptide v cc dn xut acid amin ) khng i
qua mng t bo m li gn vi cc Receptor mng t bo v to ra mt dng thc cc phn
ng Enzyme. Dng thc Adenylate dn n s tng AMP vng (AMPc) v s hot ho h
thng protein Kinase. l con ng chnh thng tin (hormone) t ngoi t bo vo trong t
bo ch .
S kt hp gia nhng thng tin th nht (hormone) vi cc Receptor s to ra nhng
tn hiu ho hc khc nhau trong t bo. Nhng tn hiu ny gi l thng tin th hai. Ngoi
AMP vng cn c mt s cht thuc thng tin th hai khc nh GMPvng (GMPc), Inosidol
Triphosphate (IP3), Diacylglycerol hay diglycerid (DG) v Ion Ca
2+
.
i vi cc hormone khng ho tan trong nc (Hormone Steroid, hormone sinh
dc...) chng c th i qua mng t bo gn vi cc Receptor ca chng trong t bo cht
hoc trong nhn t bo to thnh phc hp hormone-Receptor, th thng tin th hai (thng tin
ni bo) l phc hp hormone-Receptor.
C hai c ch tc dng c bn ca hormone l:
Tc dng ln mng
Tc dng ln gen
3.2.1. C ch tc dng ln mng: S tin ho ca sinh vt c mt bc quan trng l
vic hnh thnh ln mng, mt s chuyn bin v cht lng: T cht khng sng sang cht
sng. Bn thn mng l mt cu to chc nng hon chnh ca t bo, nn cc tc dng iu
chnh ca hormone phn ln l tc ng thng qua mng, trn mng c cc cu to cm th
(Receptor), cc cu to ny rt a dng, chc nng phong ph nhng nhn chung l chng c
cu trc c th ng vi chc nng, tnh c th ca n ht sc cao. Hormone l nhng yu t
i ti tc ng ln cc im cm th c th ca mnh. Cu trc ho hc ca hormone thng
ph hp tng ng vi cu trc ca cc im cm th. Khi tn hiu (cc phn t hormone)
n, im cm th tip nhn th qu trnh tip theo trong t bo l: a s chng tc ng ln
h thng enzyme Adenylatcyclase bin h thng enzyme ny t trng thi khng hot ng
sang trng thi hot ng hoc ngc li, v d nh tc ng ca Adrenalin nh sau:
Adrenalin
Adenylatcyclase ----------------------> Adenylatcyclase
(khng hot ng) (hot ng)
Di tc dng ca Adenylatcyclase n chuyn ho ATP 3
/
, 5
/
- AMP vng + PiPi
Mt s hormone nh atrial natriuretic factor (ANF), hay ni c t vi khun ca
E.coli... khi n im cm th ca mnh th n li tc ng ln h thng enzyme Guanylat-
cyclase (GC) chuyn GTP thnh 3
/
, 5
/
- GMP vng.
ANF cn gi l atriopeptin hay yu t bi xut Na
+
. ANF c bi tit bi t bo tm
nh ca tim khi c th tch mu tng. ANF c mu a ti thn, hot ho GC t bo ng
thu ca thn, GMP vng tng gy kch thch s bi xut Na
+
bi thn km theo bi xut nc.
S mt nc lm gim th tch mu v h p lc ca mu.
C trn ca mch mu cng cha cht th th ca ANF. ANF sau khi kt hp vi cht
th th ca n y s lm gin mch v h huyt p.
Mt th th GC tng t cng c mng t bo biu m ca rut. Th th ny c
hot ho bi ni c t ca vi khun E.coli. S tng GMP vng gy gim ti hp thu nc
biu m rut, dn n a chy c hiu do c t.
ATP
3
/ // /
, 5
/ // /
- AMPvng
Hnh 4.6. S hnh thnh cc thng tin ni bo AMPvng, GMPvng v tc dng truyn
tin qua trung gian l cc protein kinase tng ng ( A hoc G)

Nh vy l cc thng tin th hai (thng tin ni bo c hnh thnh) (Hnh 4.6).
T cc thng tin ni bo ny s tc ng ln h thng enzyme protein-kinase, ri t
tc ng ln h thng enzyme cn tc ng cui cng. ng ch l qu trnh tc ng ny
thc hin theo phn ng dy chuyn v c s khuych i. T mt phn t hormone c th
to ra hng trm phn t 3
/
, 5
/
- AMP vng v to thnh hng nghn phn t protein-kinase
hot ng v.v.(Hnh 4.7).
Nghin cu qu trnh iu chnh hm lng ng trong mu ta s thy v c ch tc
dng ln mng ca hormone. Hm lng glucose trong mu ca ng vt c v l n nh, n
giao ng trong mt phm vi nht nh gi l hng s ho sinh c th.
Hnh 4.7. S khuch i ca thng tin khi hormone kt hp vi Receptor ca mng t bo
ngi l: 80 - 120 mg%, ln: 80 - 120 mg%, tru b: 40 -70 mg%, gia cm:
150 - 300 mg%...
iu ho s n nh ny l do mt s hormone nh Insuline c tc dng lm gim hm
lng ng trong mu khi hm lng ng tng, Adrenalin v glucagon lm tng hm
lng ng trong mu khi hm lng ng ny gim. V d khi hm lng ng trong
mu gim th Adrenalin c tit ra chng n tc ng vo t bo c v t bo gan. t bo
gan qu trnh din ra nh sau: Khi n t bo gan chng tc ng ln im cm th ca n,
im cm th ny sau khi tip nhn Adrenalin s tc ng ln Adenylatcyclase chuyn
enzyme ny t trng thi khng hot ng sang trng thi hot ng, khi hot ng chuyn
ho ATP thnh 3
/
, 5
/
- AMP vng, 3
/
, 5
/
- AMP vng tc ng ln h thng enzyme protein-
kinase bin n thnh hot ng, h thng ny li tc ng ln enzyme phosphorylase chuyn
chng t trng thi b khng hot ng sang trng thi a hot ng, enzyme ny s chuyn
ho Glycogen thnh Glucose 1-p. Glucose 1-p c enzyme isomerase chuyn thnh Glucose
6-p. Glucose 6-p c enzyme phosphatase ct gc phosphate thnh Glucose a vo mu
(Hnh 4.8).
3
/
, 5
/
- AMP vng ngoi tc ng ln h thng enzyme phosphorylase qua h thng
protein-kinase I, n cn tc ng ln h thng protein-kinase II. H thng enzyme ny hot
ng s tc ng ln h thng enzyme glycogen syntetase, chuyn chng t trng thi hot
ng sang trng thi khng hot ng lm ngng qu trnh sinh tng hp glycogen t glucose.
Nh vy protein-kinase l mt enzyme cha kho trong lin h gia AMPvng vi h
thng enzyme phosphorylase v glycogen syntetase.

Enzyme protein-kinase l mt phc hp CR gm bn tiu phn, hai tiu phn xc tc C
(catalytique) v hai tiu phn iu ho R (regulatrice). Dng khng hot ng ca n, bn tiu
phn ny lin kt vi nhau, tiu phn iu ho c ch tiu phn xc tc. S iu ho hot
ng ca n l 3
/
, 5
/
- AMP vng. 3
/
, 5
/
- AMP vng gn vo tiu phn iu ho lm cho phc
hp CR tch ri nhau. Tiu phn C c gii phng v pht huy tc dng xc tc (Hnh 4.9).
Di tc dng ca tiu phn C, h thng enzyme phosphorylase s c chuyn t dng
dime (dng b) khng hot ng sang dng tetrame (dng a) hot ng. Enzyme ny hot ng
n s xc tin qu trnh phn gii glycogen thnh glucose a vo mu.

Hnh 4.8. S tc dng ca adrrenalin trong vic lm tng hm lng glucose trong
mu t bo gan
Tiu n v xc tc Tiu n v iu ho
Tiu n v xc tc (C) Phc hp AMP
c
v
hot ng tiu n v iu ho (R)
Hnh 4.9. S hot ho protein kinase ca AMP vng
Khi hot ng xong 3
/
, 5
/
- AMP vng b phn hu bi enzyme phosphodiesterase theo
phn ng thu phn:
phosphodiesterase
3
/
, 5
/
- AMP vng + H
2
O ---------------------------------> Adenozin 5
/
phosphate.
Hot tnh ca phosphodiesterase ph thuc vo Mg
+2
phn ng ny xy ra t bo cht.
Mt s cht nh cafein ca c ph, ch; nicotin ca thuc l... c tnh cht c ch enzyme
phosphodiesterase, dn n ko di s tn ti ca 3
/
, 5
/
- AMP vng lm tng qu trnh trao
i cht ca t bo gy nn s tnh to.
3
/
,5
/
- AMP vng b phn hu th cc tiu phn ca protein kinase li kt hp vi nhau
thnh phc hp ban u CR khng c hot tnh xc tc. Bng con ng ny cc h thng
enzyme do chng iu khin li tr li trng thi ngh bnh thng.
Mt s ln hormone lm tng nng ca 3
/
,5
/
- AMP vng trong cc m bo ch,
v chng c th kt hp vi cc Receptor ca n trn b mt ca t bo ch v kch thch
Adenylatcyclase gn trn mng. l cc hormone ca thy trc tuyn yn nh ACTH, LH,
FSH, TSH, cc hormone cn gip trng v calcidonin, hormone ca thu sau tuyn yn nh
Vazopresin lm tng 3
/
,5
/
- AMP vng trong thn. Mc d nhiu hormone c s kch thch to
3
/
,5
/
- AMP vng nhng mi hormone li c dng c hiu bi v n kch thch to 3
/
,5
/
-
AMP vng ch trong nhng t bo c cha cc Receptor b mt c hiu cho hormone .
Mt khc 3
/
,5
/
- AMP vng cng ch tn ti trong nhng t bo c kch thch v khng
a vo mu gy nn s kch thch chung cho tt c cc t bo. Song mt qu trnh phn
ng li c th c nhiu hormone kch thch. V d i vi lipase m m c th do cc
hormone Adrenalin, Glucagon, ACTH, TSH v.v.. cc hormone ny u lm tng s hnh
thnh 3
/
,5
/
- AMP vng trong m m v kch thch Lipase.
3
/
,5
/
- AMP vng cn l mt cht trao i trung gian (mediator) c hiu hoc mt thng
tin vin (messenger), mt dng khc ca h thng iu ho trong cc t bo. N tc dng
trung gian vo vic lm cm ng s tng hp Enzyme, tham gia vo s dn chuyn synap
trong h thn kinh, gi chc nng iu ho trong s phn chia t bo; l mt cht trung gian
(mediator) trong phn ng min dch v chng nhim trng ca cc m bo k c phn ng d
ng. c t Cholera gy s a chy t v lm mt dch trong ng tiu ho l do c t ny
gn vo cc Receptor c hiu trong t bo ng tiu ho to ra 3
/
,5
/
- AMP vng nng
cao. 3
/
,5
/
- AMP vng ny lm tng qu trnh bnh l do nh hng ti qu trnh vn
chuyn tch cc trong cc t bo ng tiu ho.
Chc nng ca 3
/
,5
/
- AMP vng trong cc t bo khc nhau c th b nh hng bi hai
yu t l Ca
2+
t do v Prostaglandin. Trong mt s trng hp Ca
2+
lm tng cng s tc
ng ca 3
/
,5
/
- AMP vng, trong mt s trng hp khc n li ng vai tr c ch.
Prostaglandin A1 c coi l thng tin vin trung gian gia Receptor-hormone b mt t bo
v Adenylatcyclase. Mt khc n li c ch Adenylatcyclase ca t bo ng tiu ho do n
gn vo v tr c hiu trn enzyme ny.
V Receptor mng: y l Receptor c phn b trn mng t bo, i tng tip nhn
ca n c bn cht l protein v nhng hp cht khc ho tan trong nc. Chng tip nhn cc
hormone ny ngay trn mng t bo ri chuyn thng tin vo trong t bo qua s tc ng ln
cc h thng enzyme to nn cc nucleotide vng v thng thng qua h thng protein G.
Protein G bao gm mt h G protein gm nhiu tiu n v nh , v . Cu to tng qut
ca n nh hnh 4.10.
Vai tr ca protein G c tc dng iu ho s hot ng gia hormone vi enzyme to
nn cc nucleotide vng thng qua s kt hp ca GTP hay GDP. Khi c mt ca hormone th
GTP kt hp vi tiu n v lm tiu phn ny tch khi phc hp , v v tr thnh
hot ng, n s hot ho Adenylatcyclase bin ATP thnh 3
/
,5
/
- AMP vng. Khi khng
c mt hormone, GDP s kt hp vi tiu n v qua phn ng thu phn GTP thnh GDP
v cc tiu n v , v ca protein G li kt hp vi nhau tr thnh khng hot ng
(hnh 4.11).
Nh vy s truyn thng tin t tn hiu hormone qua enzyme Adenylatcyclase gm 2
bc
Bc 1: Mt phn t hormone kt hp vi mt Receptor xc tc hot ho nhiu phn t
Gs.
Bc 2: Mt phn t Gs hot ho Adenylatcyclase xc tc s tng hp nhiu phn t
AMP vng. Hiu qu ca dng thc phn ng lin tip l s khuych i rt c ngha ca tn
hiu hormone .
AMP vng l mt truyn tin ni bo th hai trong h thng truyn tin, n c i sng
ngn v nhanh chng b phn hu bi phosphodiesterase thnh 5 AMP, cht ny khng c
tc dng ca cht truyn tin th hai, v tn hiu ni bo ch tn ti khi Receptor cn c lin
kt vi Adrenalin. Nng AMP vng tng hay gim l ph thuc vo nng hormone v
tc dng ca hormone cng thay i tu thuc tng m: Glucagon gy tng cao nng AMP
vng gan nhng t gy thay i nng AMP vng c.
Hnh 4.10. Cu to ca h thng Receptor v protein G
AMPc s tc dng trc tip trn protein kinase ph thuc AMPv, cn gi l protein kinase
A. Protein kinase A ny hot ho bi AMPc xc tc s phosphoryl ho phosphorylase. Cng cn
lu rng mt s hormone li c ch Adenylatcyclase lm gim nng AMPc v lm gim qu
trnh phosphoryl ho protein. Chng hn nh Somatostatin khi kt hp vi Receptor c hiu th
protein G c ch (Gi) c hot ho lm c ch Adenylatcyclase. Nh vy Somatostatin lm i
trng vi tc dng ca Glucagon.
Cc tn hiu ngoi t bo (tn hiu th nht ) hormone c th c tc dng hon ton khc
nhau nhng t bo hoc m khc nhau, tu thuc vo loi Receptor, loi protein G Gs hoc Gi
-c gn vi Receptor v mt lot cc enzyme c th c phoshoryl ho bi protein kinase ph
thuc AMP vng mi loi t bo hoc m .
1. Gs kt hp vi GDP b ngt, khng hot ng .
2. Gs tip xc vi phc hp Hormone Receptor, thay th lin kt vi GDP bng GTP .
3. Tiu phn - GTP c tch ra v hot ho Adenylatcyclase .
4. GTP b phn hu bi GTPase thnh GDP trong Gs. Gs() t ngt, tiu n v
khng hot ng kt hp li vi tiu n v v .
3.2.2. C ch tc ng ln gen.
T lu ngi ta nghin cu v s bin thi ca cn trng. iu g gy ra s bin
thi ny, l do hormone Ecdizon c ngun gc t Steroid. Thc t hormone ny nh
thc gen tng hp nhng protein cn thit v c ch cc gen khng cn thit khc trong qu
trnh bin thi ca cn trng.
Nhng cng trnh nghin cu gn y cho nhng hiu bit su sc v c ch ho
sinh ca cc hormone Steroid cng nh cc hormone ho tan trong lipid khc. Cc hormone
Steroid bao gm Estrogen hay l hormone n tnh trong quan trng nht l Estradiol v
Estron, Androgen hay hormone nam tnh nh Testosterone, Dihydrotestosterone; hormone
thai nghn Progesteron; hormone Steroid ca v thng thn nh Cortiol, Corticosterone
(hnh 4.12). Cc hormone gii tnh tc ng rng trn cc c quan gii tnh, cc hormone ca
v thng thn thng c tc dng su ln s trao i cht ca nhiu m bo, nht l s trao
i protein.
Hnh 4.11. S hot ng iu ho ca protein G
Hnh 4.12. Cng thc ca mt s hormone Steroid
Ngi ta chng minh rng cc hormone Steroid gn vi cht tip nhn c hiu ca
n trong t bo cht to thnh phc hp trung gian Receptor-hormone ri xm nhp vo nhn
t bo. Phc hp trung gian Receptor-hormone s ng vai tr gii c ch gen ng thi lm
tng hot tnh ca m-RNA polimelase. Gen c gii phng s tham gia vo qu trnh sao
chp to ra cc m-RNA, t cc m-RNA ny thng qua qu trnh phin dch to ra cc
enzyme hoc protein chc nng tng ng. Chnh nhng cht ny s xc tin cc qu trnh
iu chnh trong t bo (hnh 4.13). E.V. Jensen v cng s nghin cu Estrogen, ng
nghin cu s phn ca Estradiol phng x c tim vo ng vt ci cha trng thnh vi
mt liu lng nh, nhng hormone nh du ny c nh v vo t cung v m o, l
cc ch tc ng ca Esterogen. Esterogen nh du khng nhng tm thy t bo cht m
cn tm thy nhn t bo n c nh v chromatin. Cc nghin cu ca J.Gorski
chng minh protein tip nhn Esterogen c mt t bo cht dng dime c lng 4S khi
gn vi Esterogen n chuyn sang dng c lng 5S. Phc hp Receptor- Estrogen 5S c
tm thy nhn t bo n c nh v choromatin.
Thng qua cc quan im tng t ngi ta tm ra cc protein cht tip nhn ca
cc hormone Steroid khc nh Receptor cho Androgen trong tin lit tuyn, cc Receptor
hormone v thng thn, ca progesteron v.v.. O Mallay v cng s thc hin cc nghin
cu tm hiu s tc ng ca n tip theo qu trnh gn ca progesteron l s di chuyn ca
phc hp progesteron - Receptor t t bo cht vo nhn t bo, phc hp ny gn vi
chromatin gy s tng hot tnh ca m-RNA polimerase v tng qu trnh hnh thnh m-RNA
cho mt vi protein to nn mt lng ln protein vi trng nh albumin trng.
Hnh 4. 13. M hnh chung v c ch tc dng ca hormone Steroid
Bc 1: Hormone Steroid kt hp vi protein vn chuyn n t bo ch, ti y n tch khi
protein vn chuyn sang dng t do.
Bc 2: Vo trong t bo cht hoc nhn t bo bng khuch tn t do.
Bc 3: Kt hp vi Receptor bo tng (trng hp cc corticoid chuyn ho ng nh
cortisol) hoc Receptor trong nhn nh progesteron.
Bc 4: Hot ho Receptor: kt hp vi Receptor lm tch protein c ch Receptor ( bo tng)
hoc kt hp vi Receptor lm l im tc ng ca Receptor (trong nhn).
Bc 5: Sau qu trnh hot ho, Receptor t bo tng vo nhn
Bc 6: Kt hp vi DNA ca nhn vng c i lc cao vi DNA. v tr ny, phc (H-R) hot
ho polymerase, kch thch s sao chp, to thnh m-RNA.
Bc 7: m-RNA mi c tng ra ngoi nhn vo bo tng thc hin s tng hp protein
mi.
Bc 8: Protein mi c tng hp lm thay i chc phn v chuyn ho ca t bo.
V c ch tc dng ln gen c hai gi thit:
Ga thit th nht theo quan im ca Jacob v Moned v thuyt operon, gi thit ny
cho rng hormone Steroid s thm nhp vo t bo cht v kt hp vi protein tip nhn to
thnh phc hp. Phc hp ny di chuyn vo nhn gii phng d th bng cch kt
hp vi cht c ch ang bm trn phn gen khi ng (operator) lm v hiu ho cht c ch
ny, gii phng gen khi ng v qu trnh tng hp m-RNA c bt u. Nh vy
trong qu trnh ny hormone ng vai tr l cht gii phng (hnh 4.14).
Hnh 4. 14. S c ch tc dng ln gen ( Theo Jacob v Mon
Gi thit th hai: (theo Langan (1968) ng gii thch vai tr gii phng d th ca
hormone thng qua hot ng trung gian ca 3
/
5
/
- AMP
c
. Langan cho rng cht c ch trong
operon l histon- mt protein kim tnh mang in dng, ngc li operator mang in tch
m (v n l acidnucleic) do histon bm vo operator theo lc ht tnh in. Khi phc hp
hormone Receptor xm nhp vo t bo ch chng s hot ho enzyme adenylaxyclase
chuyn ho ATP thnh 3
/
5
/
- AMP
c
. 3
/
5
/
- AMP
c
li hot ho enzyme histonkinase lc ny
histon c phosphoryl ho sang dng histonphosphate. Cht ny mang in tch m do
chng b y khi operator. Kt qu tip theo ging nh gi thit I (hnh 4.15)
4. Mt s hormone v vai tr ca chng
4.1. Adrenalin v v Nor adrenalin
Adrenalin v v Nor adrenalin l hai hormone ca min tu thng thn c bn cht l
dn xut ca acid amin Tyrosine, c vai tr iu ho hm lng ng trong mu khi hm
lng ng ny gim. Nor adrenalin c chc nng ging nh Adrenalin nhng c hot lc
thp hn.
Qu trnh tng hp Adrenalin v Nor adrenalin nh sau:

Kh cacboxyl Hydroxyl ho Metyl ho
Tyrosine ------------> Tyramin ------------> Noradrenalin --------> Adrenalin
- CO
2
+ 2 OH + CH
3

Tyrosine Tyramin Noradrenalin Adrenalin
Hnh 4.15. S c ch tc dng ln gen (theo Langan)
Khi Adrenalin c tit vo mu n s gy ln mt lot p ng ng vt c xng
sng nh tng p lc ca mu nht l vnh ngoi vi, tng nhp tim, tng co bp tim, tng
lng mu i ra v tng huyt p. c trn, n lm th gin c t cung, c bng quang, c
hng, c chu trnh ca rut v c bao bc tiu ph qun ca phi.
Tc dng ni bt v quan trng nht v mt ho sinh ca Adrenalin lm tng tc
phn gii glycogen c to lactat v tng s phn gii glycogen gan to ra glucose
a vo mu lm n nh hm lng ng trong mu khi hm lng ny b gim. Hiu
ng ny nm 1950 c E.W. Sutherland pht hin khi ng trn Adrenalin vi m gan
c ct nh nhng cn nguyn vn th thy glucose xut hin trong mi trng dch treo.
Cng t quan st ny ngi ta tm ra 3
/
,5
/
- AMP vng v c ch tc dng ca Adrenalin
vi cc cng trnh nghin cu ca C.F. Cori, E.G. Krebs, E.H.Fisher, E.W. Sutherland.
Adrenazin chng nhng kch thch s phn gii glycogen m n cn c ch s tng hp
glycogen thng qua vic c ch h thng enzyme glycogen-syntetase. Kt qu u nhm mc
ch tng hm lng glucose trong mu. Ngoi tc ng thc y s phn gii glycogen gan
to thnh glucose, c, xng to thnh lactat, n cn kch thch lipase trong cc t
bo lipid phn gii triacylglyxerol to thnh cc acid bo gn vi abumin huyt thanh.
V c ch tc ng ca Adrenalin v Nor adrenalin l tc ng ln mng, thng qua cc
Receptor c hiu ca chng, t tc ng ln h thng enzyme Adenylatcyclase to
thnh 3
/
,5
/
- AMP vng.
Receptor ca Adrenalin t bo ch c hai loi v . Tu theo mi loi m
Adrenalin c tc dng khc nhau. i vi Receptor t bo da, s p ng ca Adrenalin
th hin s co lin kt (s s hi lm mt b ti nht), trong khi vi Receptor , s p
ng ca Adrenalin li l s dn mch (s hng phn lm m ng hng).
Khi ngng tit Adrenalin ca min tu thng thn th vic gn Adrenalin ln mng t
bo cng b gin on. 3
/
,5
/
- AMP vng khng c to ra na, s cn li th b phn hu bi
enzyme phosphodiesterase. Cc tiu n v ca protein kinase li kt hp tr li thnh phc
hp khng c hot tnh xc tc v mi trng thi tr li bnh thng. Adrenarin c phn
gii gan do enzyme monoamin oxydase.
4.2. Glucagon:
Glucagon cn c gi l hyper glycemia-glycogenolytic hormone (hormone lm tng
s phn gii glycogen).
Glucagon l hormone do t bo anpha ca o Langerhans ca tuyn tu tit ra, n l
mt polipeptide gm 29 gc acid amin:
H
2
N - His. Ser. Glu. Gly. Tyr. Phe. Tyr. Ser. Asp. Tyr. Ser. Lyz. Tyr. Leu.Asp. Ser.
Arg.Arg. Ala. Glu. ASP. Phe. Val. Glu. Try. Leu. Met. ASP. Tyr.
Khi mi tit ra dng proglucagon khng c hot tnh c thm 8 gc acid amin u
COOH, tc l c 37 acid amin. Trc khi vo mu n t ct b 8 gc acid amin ny v tr
thnh glucagon c hot tnh. Tc dng ca glucagon ging nh Adrenalin nhng chng ch
pht huy tc dng gan, n phn gii glycogen gan y mc glucose huyt v mc bnh
thng, khi hm lng glucose trong mu gim. Glucagon khng pht huy tc dng c. C
ch tc dng ca n ging nh Adrenalin thng qua 3
/
,5
/
- AMP vng. Glucagon c phn
gii ch yu gan.
4.3 Insuline
Insuline l mt hormone do t bo ca o Langerhans ca tuyn tu tit ra. N gi
vai tr quan trng trong qu trnh iu ho hm lng ng trong mu, n lm gim hm
lng ng khi hm lng ny tng.
4.3.1. Cu to ho hc, s tng hp, d tr v s tit ca Insuline
Cu trc ho hc ca Insuline c xc nh t nm 1953 do Sanger (gii thng
Nobel 1958). Insuline l mt hormone protein gm hai chui vi 51 acid amin (KLPT: 5.700
dalton). Khi mi tit ra di dng proInsuline. ProInsuline gm 3 chui: Chui A gm 21
acid amin, chui B gm 30 acid amin, gia 2 chui ny c hai cu ni disulfid. chui A c
1 cu disulfid. Gia chui A v B l chui C. Chui C gm c 30 acid amin, n c ni vi
chui A v B bi 2 cp acid amin kim tnh (arg.arg v arg.Lyz) (hnh 4.16). ProInsuline
khng c hot tnh. Khi c nhu cu v Insuline n c enzyme peptinase ct b chui C v
to thnh Insuline c hot tnh. Insuline nhng ng vt khc nhau th khc nhau ch yu
chui A v tp trung vo cc acid amin 8,9,10, 12 v 14, cn chui B hu nh ging nhau,
khc nhau ch yu acid amin 30. Do c th dng khc loi song hiu qu khng cao.
S tng hp Insuline.
Polypeptide u tin sn sinh ra Insuline l pre-proinsuline (tin-tin Insuline). Pre-
proInsuline c cha thm mt chui khi u gm 23 acid amin. Chui ny c tc dng nh
mt chui tn hiu hay cn gi l chui khi u gip cho Insuline c tng hp bi
polyribosom. S ct ngn pre-proinsuline thnh proinsuline xy ra trong li ni cht nguyn
sinh. Sau proinsuline c chuyn ti cc b cha ca b my Golgi. n c ct
chui peptide C. S to thnh Insuline t proinsuline tip tc nang bi tit. y chng
c kt tinh vi Zn
2+
theo mt trnh t nht nh. Khi nhn c tn hiu no gy ra s
tng ng huyt, lc ny cc b cha s gii phng Insuline v chui C vo mu bi hin
tng m bo.
Ion Ca
2+
gi vai tr quan trng trong vic gii phng Insuline. Trong mu Insuline v
peptide C chim khong 94%, cn proinsuline chim khong 6%. Lc bnh thng nng
Insuline trong mu v trong cc m rt thp n ni nhng phng php tiu chun hoc cc
thc nghim sinh hc kh thc hin hoc xem xt vic tit cng nh ng dng ca n. Tuy
nhin bng phng php ng v phng x cc nhy ngi ta thy mu c cha khong 0,4
g Insuline trong mt ml lit. Sau khi n thc n giu ng Insuline c th tng 3-4 ln so vi
mc k trn. Tuyn tu bnh thng ca ngi c cha khong 10 g Insuline, nhng lng
tit vo mu hng ngy ch khong t 1-2g. S gii phng Insuline khi tuyn tu ph thuc
vo nng glucose trong mu v mt s yu t khc. Khi glucose huyt tng cao hn bnh
thng th cc b tit tin ti gn mng nguyn sinh cht ca t bo tun vo mu Insuline
(hnh 4.17).
Chui B
Phe Val Asp Gly His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu
ARG
S S Gly
Phe
S S Phe
Tyr
Chui A Thr
Ile Val Glu Gln Cys Cys Ala Ser Val Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Pro
Gly S S Lys
Arg Ala
Lys Arg
Gly Arg
Pro Glu
Pro Chui C Val
Gly Glu Leu Gly Gly Ala Gly Pro Gly Gly Ala Leu Glu Leu Ala Gly Val Llu Pro Gly Glu
Hnh 4.16. Cng thc cu to ca Proinsuline
Nng Insuline trong mu sau li gim ti mc bnh thng trong chu trnh na
gi hoc 2 gi sau ba n. Khi tit vo mu Insuline c vn chuyn bi 1 loi protein v
mt phn vi mng ca hng cu. Sau khi hot ng xong Insuline b phn hu bi
Insulinease, qu trnh ny ch yu din ra gan v thn. S gii phng Insuline cng c
kch thch bi mc tng ca acid amin v mt s yu t c hiu tit ra t d dy v rut.
M hnh 4.17. S tng hp v bi tit Insuline t bo ca tuyn tu
4.3.2. Tc ng ca Insuline ln m bo ch
Tc dng r rng nht ca Insuline vi ng vt c v l gim nhanh chng hm lng
glucose trong mu khi hm lng ny tng, do vic tng cng vn chuyn glucose vo mu
qua t bo c, gan, lipid. Insuline c tc dng chuyn dng ca enzyme glycogen syntetase t
khng hot ng sang trng thi hot ng xc tin qu trnh sinh tng hp glycogen t
glucose t bo c, t bo gan. ng thi n c ch s phn gii lipid. Mt enzyme khc
chu tc ng r rt ca Insuline l Hexokinase - enzyme c vai tr hot ho glucosse.
Glucose sau khi c hot ho s i vo con ng cung cp nng lng cho t bo v mt
phn to nguyn liu cho qu trnh tng hp lipid. Insuline cn thc y s tng hp protein
t cc acid amin, ng thi n ngn cn nhm hormone Corticosteroid, do qu trnh sinh
mi glucose b dng li.
V c ch tc ng ca Insuline l c ch tc dng ln mng thng qua cht tip nhn
c hiu ca n mng t bo ch. Cuatracasas v cng s tch chit c cc protein
Receptor ca Insuline t cc t bo lipid khi dng cc cht ty khng ion v tinh khit
c chng bng phng php sc k i lc trn cc ht Insuline-agarose. Bng sc k kh i
lc vi tnh c hiu cao ca phn ng gia Insuline vi cht tip nhn Insuline ngi ta
thu c nhng phn t cht tip nhn Insuline ho tan, v tinh khit c trn 250.000
nhm protein cht tip nhn Insuline c khi lng phn t khong 300.000 dal. Nh vy
Insuline c nhiu cht tip nhn.
Hnh 4.18. S cu trc ca cht tip nhn Insuline
Cht tip nhn ca Insuline l protein kinase c hiu vi Tyrosine, n vn chuyn mt
gc phosphate t ATP phosphoryl ho gc OH ca Tyrosine. Bn thn cht tip nhn ny
l mt mt glycoproteid, gm 2 chui (KLPT 130.000 dal). Chui nm mt ngoi mng
v cha mt v tr c hiu nhn din Insuline v kt hp vi n v 2 chui (KLPT
95.000 dal) nm gia mng, vi gc carboxyl (-COOH) pha dch bo tng. Chui c
vng hot ng Tyrosine-kinase (hnh 4.18)
Hnh 4.19. C ch vn chuyn glucosse qua mng t bo ca Insuline
Hnh 4.19. C ch vn chuyn glucosse qua mng t bo ca Insuline
Khi Insuline kt hp vi chui , chui s xc tc cho phn ng phosphoryl ho gc
tyrrozin c hiu ca bn thn mnh. Phn ng t phosphoryl ho v tr xc tc ca chui
lm tng kh nng phosphoryl nhng gc Tyrosine ca nhng protein bo tng ca t
bo ch. S kt hp ca Insuline vi cht tip nhn ca n lm tng tc vn chuyn
glucosse qua mng t bo (hnh 4.19).
Tc ng ca Insuline l tri ngc vi 4 hormone: glucagon, Adrenalin,
Glucocorticosteroid v hormone sinh trng ca tuyn yn. Ngoi s iu ho trao i
glucid, Insuline cn nh hng gin tip n cc qu trnh trao i dinh dng khc. Khi
thiu Insuline th ngoi s lm tng hm lng ng trong mu gy nn chng dia betes
mellidus (bnh ng niu), n cn lm gim hm lng glycogen c, gan, th xton trong
mu tng ln do s xy ho lipid tng, mt khc s tng hp chng li gim, tc phn gii
protein cng tng, iu ny c th hin tng lng nit bi tit theo nc tiu v c s
chuyn ho cc acid amin thnh glucose. Ngi ta c th gii thch s tng phn gii lipid v
protein l do t bo thiu nng lng. V khi thiu Insuline s lm gim thm thu glucose
ca t bo (hnh 4.19), lm gim hot lc ca enzyme Hexokinase. Do tha ng m t
bo li thiu nng lng. T bo phi ly nng lng t lipid v protein.
S gim xy ho glucose c chng minh qua th nghim vi cc ng v phng x.
Ngi ta a glucose c nh du bng C
14
phng x vo ng vt thiu Insuline, bng
con ng o hot tnh phng x ca kh CO
2
th ra c th xc nh c s oxy ho glucose
trong c th. Ngi ta ch thy mt phn rt nh ca C
14
trong kh CO
2
th ra, khi con vt
c tim Insuline th C
14
trong kh CO
2
th ra tng ln r rt.
4.4. Tc trao i cht c bn v hormone tuyn gip.
Tc trao i cht c bn (BMR) l tc tiu th oxy c o trn i tng sng
trng thi ngh hon ton nhng khng phi l trng thi ng. Cch ny c thc hin
trng thi sau ba n t nht l 2 gi. BMR c biu hin bng kilocalori nhit lng c
to ra hoc th tch oxy c tiu th bi 1 m
2
trong 1 gi. V n quan h trc tip gia nng
lng gii phng t s t chy cc cht dinh dng v lng oxy c tiu th, iu ny
c th hin qua phng trnh h hp RQ (Respiratory quaotient).
CO
2
RQ = -------
O
2
Ch s RQ ca mt s cht dinh dng nh sau (bng 4.2).
Bng 4.2. Ch s RQ ca mt s cht dinh dng
Nhin liu RQ W to ra ca 1g
nhin liu (Kcal)
Lng O
2
tiu tn
(lit)
Glucid 1,00 4,18 5,05
Lipid 0,71 9,46 4,69
Protein 0,80 4,32 4,46

Hormone iu ho trao i cht c bn l hormone ca tuyn gip bao gm 2 cht chnh
sau l:
Triiodotyronin T
3
(L 3,5, 3
/
triiodotyronin) v Tetraiodtyronin (Thyroxin) T
4
(L 3,5,3
/
5
/
- tetraiodotyronin)
Khi gim hot ng ca tuyn gip th s trao i cht c bn gim xung, s bi tit
nit gim. Ngc li khi tng hot ng ca tuyn gip th s trao i cht c bn tng, s bi
tit nit tng. Nhng thay i trong vic sn xut hormone ca tuyn gip ca con ngi u
dn ti nhng trng thi bnh l sau:
Khi nhc nng tuyn gip dn n chng n n v ph nim (myxoedema) tr
nh, cn ngi ln l ph nim. Nhng nt c trng ca bnh l tm vc ln, pht trin
chm, tnh lnh lng, ni chm, hot ng tr c thp, mt trn, li to, mi sng dy. Ngoi
ra cn c triu chng ph, n mt ngon.
Khi u nng tuyn gip l kt qu ca s sn xut hormone tng ln ca tuyn gip. Cc
triu chng ca trng thi ny l s trao i cht c bn tng cao, c th gy i nhanh, nhp
tim cao, tng tc chy mu, i khi xy ra li mt, bn thn tuyn gip tng to ln
(Struma).
Bnh bu c l do s ln ln vi mc cao ca tuyn gip. C s ca bnh ny l s
xm nhp khng y iod vo c th, do vy m lp biu b tuyn gip tng mt cch u,
bnh ny thng gp cc a phng m trong thc n, nc ung thiu iod.
Hot ng tng ln hay gim xung ca tuyn gip ph thuc vo yu t c nh hng
ti nhng hot ng ca n: H thn kinh trung ng nh hng n s trao i cht bng s
thay i hot ng ca tuyn gip, n tc ng thng qua hormone tyreotropin (TSH) ca
tuyn yn, hormone ny mt mt lm tng s tch lu iod trong tuyn gip mt khc c th
lm tng cc t bo ni tit hipeplazi ca tuyn gip t lm tng s hot ng ca tuyn
ny.
S tiu th oxy ca hu ht cc m bo, u b nh hng ca hormone tuyn gip tr
no, tc tiu th xy ca no khng b nh hng bi trng thi ca tuyn gip.
Thyroxin v 3,5,3
/
triiodtyronin l nhng dn xut iod ca Tyrosine. Mc d Thyroxin
c to ra nhiu hn triiodtyronin nhng triiodtyronin li c hot tnh cao hn 5-10 ln.
Ngi ta chng minh c rng cc iodua khi xm nhp vo c th u c tuyn
gip thu ht rt mnh, so vi nng ca cc iodua trong mu th nng ca chng trong
tuyn gip ln hn ti 25-500 ln. T cc iodua, nh kh nng oxy ho ca tuyn gip to
thnh iod. T cc iod thu c ny di nh hng ca enzyme c hiu m n iod ho
(IOD) cc gc Tyrosine ca tireo Globulin. Cn nh rng iu ny khng xy ra i vi
Tyrosine t do trong tuyn gip m n ch ring cho Tyrosine trong protein ca tireoglobulin.
Tireo globulin c iod ho s c catepxin c hiu ca tuyn gip phn gii to
thnh ng thi Thyroxin v triiodtyronin. mu Thyroxin v triiodtyronin c lin kt vi
cht vt chuyn l TBG (Thyroxin binding globulin). Sau khi hot ng xong chng c
phn gii bi enzyme dehydrogenase gii phng iod, iod ny c xm nhp li ti s
dng.
mt s trng hp chng n n c di truyn v nhng ngi ny khng c
nhng enzyme c hiu tham gia trong qu trnh sn xut hormone ca tuyn gip nh trng
hp khng c enzyme oxy ho cc iodua thnh iod, mt s trng hp li khng c enzyme
ngng t cc iod tironin thnh Thyroxin, hoc khng c enzyme dehydrogenase nn khng c
qu trnh ti s dng c iod, kt qu l mt iod dn n thiu Thyroxin.
V c ch tc dng: C ch chnh xc v s kch thch tiu th oxy ca Thyroxin cha
c r, nhng ngi ta bit Thyroxin thc y s lm tng nng ca mt vi enzyme
c lin quan n h hp, c bit l glyxerol -3-phosphate dehydrogenase ca ty th, mt
enzyme dehydrogenase c chc nng trong chui h hp. Ngi ta thy rng trong trng
hp nhng con chut b u nng tuyn gip th ch s P/O gim (tc l nng lng i vo tch
lu to thnh ATP gim v to ra nhit nng tng). Tc dng ny cng c chng minh c
trong invidro, khi cho thm Thyroxin hoc triiodtyronin th t s P/O trong cc ty th ca gan
gim xung, trong khi s s dng oxy li tng ln. Ngoi ra Thyroxin cn gy nn s bin
thi ca nng nc, bng phng php phng x ngi ta thy rng Thyroxin phng x gn rt
mnh vi chromatin t bo gan ca nng nc, iu dn ti gi nh cho rng chc nng
ca Thyroxin lm ni lng cc gen c hiu.
YU CU CN NM
CHNG IV : HORMONE
Khi nim, vai tr sinh hc ca hormone v mi lin h thn kinh -th dch
Phn loi hormone. C ch tc dng ca hormone
Cu 1: Khi nim, bn cht v vai tr ca hormone?
Cu 2: Hormone l g? Vai tr sinh hc ca Hormon?
Cu 3: Phn loi hormone? Cho bit nguyn l v c ch tc dng ca hormone?
Cu 4: Receptor v cc thng tin ni bo?
Cu 5: C ch tc dng thng qua mng ca hormon?
Cu 6: C ch tc dng thng qua gen ca hormone?

CHNG V
TRAO I VT CHT V NNG LNG
1. Trao i vt cht l g?
Bt c mt sinh vt no cng tn ti trong mt mi trng nht nh, c khng gian v
thi gian nht nh v c quan h cht ch vi mi trng m n sng. Sinh vt v mi trng
l mt h thng thng nht, n chu s chi phi ca mi trng, da vo mi trng sng,
ng thi chng tc ng vo mi trng, gy nh hng ti mi trng. Hin tng trao i
i li ngi ta gi l trao i vt cht (t..v.c). Sinh vt mun tn ti c l nh trao i
vt cht. Qu trnh ny tin hnh khng ngng t lc hnh thnh c th dng phi bo n
lc gi v cht. Trao i vt cht l tiu chun quan trng nht ca hin tng sng (tr trng
thi tim sinh). Gii v c cng c t..v.c nhng qua n b hao mn. Tri li thng qua
t..v.c m gii sinh vt sinh si ny n v pht trin. S khc bit v cht lng ny xut pht
t kh nng t..v.c sinh vt c s chn lc v ci bin cc yu t ngoi cnh, n hp thu
nhng yu t cn thit ca mi trng v bin ho nhng yu t thnh dng thch hp cho
c th pht trin.
Trao i vt cht bao hm nhng ni dung g? Sinh vt thc hin t..v.c. vi mi
trng m n sng, n ly t mi trng nhng yu t dinh dng, kh O
2
, H
2
O, khong.. mt
cch c chn lc v o thi ra mi trng nhng yu t khng cn thit t trong c th, trong
qu trnh tip nhn v o thi sinh vt tc ng qua li vi ngoi cnh theo hai hng, hai
qu trnh gn cht vi nhau l qu trnh ng ho v qu trnh di ho.
Qu trnh ng ho gm nhng bc sau:
Chn lc nhng yu t t bn ngoi (lc ny chn lc c tnh cht th qua th gic,
thnh gic, xc gic, v gic...nh con vt n thc n)
X l hp thu (qu trnh tiu ho hp thu), sau qu trnh ny cc yu t ngoi cnh
c chuyn vo ni m.
T cc yu t chn lc , sinh vt kin to nn nhng yu t ca c th (enzyme,khng
th...) duy tr s tn ti v pht trin.
Qu trnh ng ho c tnh cht xy dng, thng qua qu trnh ny cc yu t ngoi
cnh bin thnh cc yu t ca c th. Cc nguyn liu thc n ly t mi trng bn
ngoi vo bin thnh nhng cht thch hp, c trng cho c th. T nhng yu t , sinh
vt xy dng ci to cc m bo, cc hot cht ca c th. i vi ngi v gia sc, qu trnh
ng ho l qu trnh s dng cc nguyn liu t thc n thu c to nn cc m bo.
Song song vi qu trnh xy dng ny, trong c th sinh vt lun lun c qu trnh th
hai, l qu trnh d ho.
Qu trnh d ho:
T trong c th ngay t bc chn lc x l hp thu c th sinh vt loi thi
nhng yu t khng cn thit, qu trnh ny c tip tc thc hin trong tng t bo loi
thi nhng yu t khng cn thit gi ci ra ngoi di dng nhng cht o thi. Qu trnh
phn gii cc cht c hin tng gii phng nng lng, nng lng ny c dng vo cc
qu trnh sng ca c th.
Hai qu trnh ny xt khi qut th c v mu thun, nhng xt v logic th y l hai
qu trnh mu thun nhng thng nht vi nhau, l hai mt khng kht ca mt vn . y l
hai qu trnh tin hnh song song tri ngc nhau, nhng h tr ln nhau, khng c ng ho
th khng c d ho v ngc li. Tht vy, qu trnh ng ho to ra mi thnh phn ca c
th trong c nhng enzyme xc tc. C nhng enzyme ny th nhng phn ng phn gii
ca qu trnh d ho mi tin hnh c, nhng mi phn ng tng hp c th u cn n
nng lng c sn sinh ra do qu trnh d ho.
Ngoi cnh (mi trng) i vi mt sinh vt l tt c nhng g bao quanh sinh vt ,
gm nhng yu t thun li cng nh yu t cn tr s tn ti ca n. Mun duy tr v pht
trin, mi ng vt phi thch nghi, phi khai thc c nhng yu t cn thit cho s tn ti.
ng ho v d ho c c th tng loi, ging, gii, tin ti tng c th sinh vt.
Cch ng ho, d ho c trng ngi ta gi l kiu trao i vt cht (k.t..v.c). Vy kiu
trao i vt cht l cch s l tip thu cc iu kin ngoi cnh mt cch c th, cch thc
hin cc phn ng ho sinh c th. Chnh kiu trao i vt cht l c s ca khi nim loi
v ging, loi ging khc nhau l do kiu trao i vt cht khc nhau. Nhng bin i trong
tin ho chnh l nhng bin i v k.t..v.c.
Kiu trao i vt cht c nn tng vt cht c th l cc h thng enzyme hay ni khc
i kiu trao i vt cht c quyt nh bi cc h thng enzyme , enzyme c bn cht l
protein nn chnh protein quyt nh kiu trao i vt cht. Enzyme hay protein l h thng c
kh nng bin i thch nghi thng qua nhng nh hng ko di ca ngoi cnh, chnh l
nn tng ca s tin ho, ca lai to ging. Khi iu kin mi trng n nh th kiu hot
ng ca cc h thng enzyme n nh v c lu li trong h thng di truyn, trong cu
trc ca DNA, nn kiu trao i vt cht l mt h thng n nh ch khng c nh v c th
thay i tu theo mc thay i ca mi trng.
Qu trnh trao i vt cht ng vt c th hin s sau (Hnh 5.1).
2. Trao i nng lng
Mt sinh vt mun tn ti c cn phi c nng lng. C th sng khc c bn vi
vt khng sng l i hi s chi ph lin tc v nng lng thc hin qu trnh sng. Sng
l qu trnh chng li Antropi
S
(
S
= q/T - nguyn l th hai ca nhit ng hc). Antropi
l hm trng thi, n ch chiu hng din bin ca cc qu trnh. Chiu hng ca cc qu
trnh t din l lun hng v pha t ti trng thi cn bng, tc l theo chiu hng th
tiu kh nng sinh ra cng, hay l san bng tha s cng (tha s khng c cng tnh nh
nhit , nng , p sut...) tc l lm cho Antropi t ti cc i. Qu trnh sng cng tun
th theo quy lut ny, do c th sinh vt mun duy tr trng thi sng th i hi phi c
nng lng duy tr Antropi trng thi cc tiu. Mun vy n phi khai thc nng lng t
cc yu t ngoi cnh nh thc n, nc ung.
Sinh vt l mt h thng m, trong c th bao gi cng tin hnh ng thi hai loi
phn ng to nhit v thu nhit, nn Antropi bao gi cng trng thi cc tiu.
Trong nhit ng hc ta bit: G = H + T. S. Trong G l bin i nng lng
t do ca h thng (tc l nng lng c kh nng sinh ra cng); H l nhit lng to ra hay
thu vo h thng, T l nhit tuyt i ca qu trnh. S l bin i Antropi. Do c th l
mt h thng m c trng thi n nh nn S coi bng 0. Do bin i nng lng t do
ca qu trnh gn ging nh hiu qu nhit tc l G H v trong thc hnh ngi ta nh
gi gi tr nng lng ca qu trnh qua nhit lng (n v l Jun, calo..).
Hnh 5.1. S ca qu trnh trao i vt cht ng vt
Giai on I
(Tiu ho, hp thu)
Giai oan II
( Chuyn ho trung gian)

Giai on III
( Oxy ho)
Protein Glucid Lipid
Acid amin ng n
(Glucose)
Glyceral Acid bo
Acid Pyruvic
Acetyl CoA
Chu trnh
Krebs
CO
2
2H
+
H
2
O
Chui h hp
ATP
2.1. Sinh vt sng bng nng lng g? Tt c sinh vt trn tri t u sng bng
nng lng chuyn i in t ca nguyn t hydro, theo con ng oxy ho kh.
Da theo cch khai thc nng lng t ngun dinh dng hu c cha cacbon, ngi ta
chia sinh vt thnh hai nhm:
Nhm t dng (Autotrophe): Nhm ny gm c quang dng: sng bng nng lng
nh sng mt tri v ho dng: sng bng nng lng ho hc (oxy ha S, F
e
...)
Nhm d dng (Heterotrophe): sng bng nng lng ca sinh vt khc.
Nhn chung ngun gc nng lng m sinh vt trn tri t s dng l nng lng nh
sng mt tri thng qua qu trnh quang hp ca cy xanh (dip lc) m quang nng bin
thnh ho nng:
h
6 CO
2
+ 6 H
2
O -------------- > C
6
H
12
O
6
+ 6 O
2
Dip lc
Xt v mt nng lng C
6
H
12
O
6
l vt cha nng lng (d tr ho nng). Trong qu
trnh quang hp, nng lng ca lng t nh sng chuyn cho e ca dip lc, e ca dip
lc nhn c h chuyn ln mc nng lng cao hn, t trng thi mc nng lng cao
n di chuyn qua cc thnh vin ca qu trnh phosphoryl ho-quang ho nh feredoxyl,
xytocrom b, f... Trong qu trnh chuyn dch nh vy n "nh" nng lng, nng lng ny
c cc thnh vin trn tch lu vo ATP (bin ADP thnh ATP), khi tr v mc nng lng
thp (mc nng lng ban u) n tr li dip lc. T cc ATP ny m t bo cy xanh tng
hp c C
6
H
12
O
6
t CO
2
v H
2
O (trong pha ti ).
Hydro nm trong phn t nc c in t mc nng lng thp, khi phn t ng
in t ca n mc nng lng cao hn, chnh nng lng nh sng c tch lu in
t c mc nng lng cao ny. Ton b qu trnh khai thc nng lng sinh vt d dng
ch l qu trnh a in t c mc nng lng cao tr v bc nng lng ban u. S nng
lng d tha c chuyn sang cc dng cn cho qu trnh sng (nhit nng, ATP...).
Qu trnh khai thc nng lng ny c gi l qu trnh oxy ho kh sinh hc v c thc
hin bi mt c ch gi l chui h hp hay cn gi l s h hp m bo.
2.2. S h hp m bo (qu trnh oxy ha-kh sinh hc)
y l cch khai thc nng lng cc hp cht hu c bao qut nht ca sinh vt d
dng, trong e cao nng ca hp cht hu c c h thp dn mc nng lng, s nng
lng d tr c gii phng ra v c ct gi di hnh thc thch ng tu theo tng sinh
vt m trc ht l vo cc lin kt phosphoryl cao nng ( P ).
Qu trnh oxy ha kh sinh hc l g? bn cht n khng khc g cc qu trnh oxy ha
kh ho hc tc l qu trnh trao i in t:
A
-e
+ B A
+
+ B
-e
( A l cht kh, B l cht oxy ha ).
Tuy nhin qu trnh oxy ha-kh sinh hc, s d l sinh hc v:
Qu trnh din ra t t, do nng lng to ra khng mnh lit, khng o t, bin i
nng lng t do ca h thng khng ln, khng gy nh hng ti mi trng t bo.
Qu trnh xy ra do enzyme xc tc, do mt h thng enzyme b tr lin hon vi nhau
thnh mt chui, mt dy chuyn nn c tn gi l chui h hp.
Qu trnh din ra trong mi trng nc (mi trng hot ng ca enzyme).
Nng lng to ra phn ln c ct gi vo cc lin kt cao nng nh ATP, UTP... S
tch lu hay to nhit ph thuc vo yu cu ca m bo.
Chui h hp c phn b mng trong ca ty lp th, mng ca dip lp th, mng
ca vi sinh vt.
Ty lp th (midochondrie) c th v nh trm in ca c th. Cu to ca n gm mng
ngoi (khng c vai tr v nng lng), mng trong gm nhiu np gp tng din tch, n
lin quan ti s lng chui h hp iu ny ph thuc vo chc nng ca tng loi m bo.
Gia hai lp mng l khong khng gian v trong cng l phn cht nn, y c DNA ring
ca ty lp th (hnh 5.2.).
Hnh 5.2. Cu to ca ty lp th ( midochondrie)
Cc thnh vin ca chui h hp:
Mt s enzyme dehydrogenase: ng vi cc c cht khc nhau c cc coenzyme NAD
+
,
NADP
+
, FAD
+
...
H thng vn chuyn in t bao gm:
H thng ubiquinon (UQ).
H thng cytocrome nh b, c
1
, c, a. a
3
...
Nhm st khng hem (Feredoxin).
Chui h hp c biu din theo s sau (hnh 5.3).
S
H
H
NAD+
NADH2 FAD+
FADH2 UQ
UQ
H+
H+ H+
H+
H+ H+
H+
H+
H+
H+
e
e
H+
H+
e
e
e
e
e e e
e
Xyt b Xytc1
Xytc Xytaa3
1/2 O
O- H2O
e
e
e
e
e
e
e
e e
e
Hnh 5.3. S ca chui h hp
C cht l cht cho cc cp H
+
cao nng, cho nng lng v d cc acid bo, cc phn t
ng...
R CH CH
H
COOH
H
----------> cp hydro c th cho
Trc ht c cht b tch H
+
do enzyme Dehydrogenase tng ng, thng bt u t
Dehydrogenase c nhm ghp l NAD
+
(Nicotin amid Adenin Dinucleotide) (hnh 5.4).
NAD
+
sau khi nhn cp H
+
v e thnh NADH
2
, n li tr thnh i tng tc ng ca
enzyme Dehydrogenase c nhm ghp l FAD
+
(Flavin Adenin Dinucleotide) (hnh 5.5).
Hnh 5.4. NAD nhn cp Proton v in t
Hnh 5.5. FAD nhn cp Proton v in t
FAD
+
nhn c cp H
+
chuyn thnh FADH
2
, FADH
2
li chuyn cp H
+
v e cho UQ
(hnh 5.6).
Hnh 5.6. Ubiquinone nhn cp Proton v in t
T UQ cp H
+
i ra ngoi mi trng, cp e i qua h thng cytocrome. Cytocrome
nhn e, nguyn t st t Fe
+3
thnh Fe
+2
, n cytocrome a
3
n s hot ho 1/2O
2
thnh O
-
, O
-
kt hp vi cp H
+
t UQ chuyn vo thnh H
2
O.
Hnh 5.7. St trong cytocrome dng oxy ho v dng kh.
cc loi vi khun ym kh, cht nhn cp Proton v e khng phi l O
2
m mi loi vi
khun ym kh c cht nhn c trng ring. V d t bo men ru cht nhn l aldehyt
axetic tr thnh ru ethylic.
CH
3
- CHO + NADH
2
CH
3
- CH
2
OH + NAD
+
Chui h hp phn b mng trong ca ty lp th v mt khng gian y l ni tip xc
vi phn cht nn l ni thc hin qu trnh oxy ho cc hp cht hu c.
Mt s enzyme nh xantin oxydase sau khi nhn cp e v Proton n chuyn cho O
2
to
thnh H
2
O
2
- l cht cn giu v nng lng, y l cht c i vi c th v n phn ly to
ra oxy nguyn t [O]. Oxy nguyn t c tnh oxy ho cao lm ph v cc mng sinh vt, c
th gii c chng bng cch tit enzyme catalase phn gii chng thnh nc v oxy phn t:
Catalase
2 H
2
O
2
-------------------> 2H
2
O + O
2
2.3. Qu trnh phosphoryl ho (qu trnh tch lu nng lng)
Nng lng gii phng ra trong qu trnh h hp m bo, mt phn to ra di dng
nhit nng si m c th, mt phn c tch lu li thng qua qu trnh phosphoryl ho.
y l qu trnh quan trng v thng qua to ra cc hp cht cao nng m in hnh l
cht ATP (Adenozin triphosphate) (hnh 5.8).
Hnh 5.8. Cu trc phn t ATP
Gc acid phosphoric mt i mt nhm OH th gi l gc phosphoryl
P O
OH
OH
HO
p O
OH
OH
~
- OH
Acid phosphoric Gc phosphoryl
Khi n nhn mt cht no th cht gi l cht c phosphoryl ho, v d cht A:
p O
OH
OH
~
A
+
p O
OH
OH
~ A
Qu trnh phosphoryl ho c thc hin bi enzyme phosphopherase (enzyme vn
chuyn phosphate) hay cn gi l kinase. Qu trnh tch lu nng lng trong c th ng vt
thng qua phn ng phosphoryl ho c thc hin theo 2 cch:
Cch 1: phosphoryl ho bc c cht: V d t acid 1,3 di P glyxeric (hnh 5.9).

Hnh 5.9. Phosphoryl ho bc c cht
Qu trnh tch gc phosphate cao nng ( P) t c cht khng qua qu trnh trao i e,
qu trnh ny hiu qu khai thc nng lng khng cao.
Cch 2: phosphoryl ho - oxy ho ( qu trnh to ATP do s chuyn i e xy ra trong
chui h hp). Vn t ra l nng lng c gii phng ra trong qu trnh h hp t cc
cp e cao nng lm th no gn c vo gc phosphoryl ( P) bin ADP thnh ATP?
Qu trnh phosphoryl ho - oxy ho l mt qu trnh rt c o trong h thng khai
thc nng lng ca t nhin. Ngi ta xc nh c v tr thc hin qu trnh ny, l
mng trong ca ty lp th, mng ca dip lp th, mng ca VSV. tt c nhng mng ny
u c mt cu trc c bit gi l cu trc hnh nm, ty lp th cu trc ny hng vo bn
trong cht nn, dip lp th hng ra bn ngoi.
Mng thc hin qu trnh phosphoryl ho - oxy ho gi l mng "hp din"
(couphingmembrane) tc l mng thc hin ng thi hai qu trnh: oxy ho cho nng lng
v phosphoryl ho tch lu nng lng (hnh 5.10).
c im ca mng hp din l: Trong mng t l protein/lipid = 2/1; Chiu dy ca
mng n nh v bng khong 70-90 A
0
; Trong mng c cha chui h hp ng thi c
cha h thng enzyme thc hin qu trnh phosphoryl ho, tc l qu trnh tch lu nng
lng do qu trnh oxy ho gii phng ra. Qu trnh to ra ATP nn h thng enzyme ny
c gi l adenozin triphosphatase (hay l ATPase). Hai qu trnh oxy ho v phosphoryl
ho bao gi cng tin hnh ng thi trong mng hp din nn ngi ta gi l 2 qu trnh
"hp din".
Bng phng php o th nng oxy ho hon nguyn v qua h s h hp P/O (P dng
este ho v O tiu th, ngi ta thy rng mi cp e v Proton qua chui h hp mang
nng lng lp c 3 ATP (P/O = 3), tc l:
2e + 2 H
+
+ O ------- > H
2
O O = 1
3ADP + 3H
3
PO
4
------- > 3ATP P = 3
Ngha l khi dng mt nguyn t oxy cho qu trnh h hp th c th thu c 3 ATP.
Ngi ta cng xc nh c 3 v tr to ra ATP, l: NAD FAD, Cytocrome b
cytocrome c
1
v cytocrome a a
3
.
T H
3
PO
4
lm th no thnh gc phosphoryl cao nng ( P) v to thnh ATP? c
nhiu gi thit nh l thuyt mng hp din ho hc ca Lehninger nm 1972 (c hp cht
ho hc trung gian X,Y,Z no nhn nng lng ca qu trnh oxy ho ri chuyn cho gc
phosphoryl); Thuyt bin hnh cu trc (c s bin hnh cu trc ca mt loi protein no
to ra th nng ri chuyn cho gc phosphoryl), nhng u khng c tnh thuyt phc.
Thuyt phc hn c l thuyt ho thm thu do Peter Midchell xng nm 1962 v c
Skonlatsov chng minh nm 1972.
Theo thuyt ho thm thu ca Peter Midchell th cp Proton c tch ra t c cht do
enzyme Dehydrogenase, sau khi n UQ c quay tr li mi trng ngoi, cp e c vn
chuyn tip xuyn qua mng vo trong. Nh vy nh hot ng ca chui h hp to nn 2
h qu quan trng l:
Th hiu in tch (gradien e), mng tr thnh mt ci t in vi in th 90-140 von,
vi chiu dy 70-90 A
0
th y l mt cht cch in tuyt vi nht trong t nhin.
Gradien nng H
+
, qu trnh oxy ho cng mnh th hm lng H
+
mt ngoi mng
cng ln, chnh gradien nng H
+
l nhn t tch li nng lng nhiu nht, n l ng lc
chnh gy l qu trnh tng hp ATP.

Hnh 5.10. Cu trc ca mng hp din v qu trnh phosphoryl ho-oxy ho
Hnh 5.11. Qu trnh to ATP theo thuyt ho thm thu ca Peter Midchell lp th
Nh vy hot ng ho hc dn ti hin tng bn thm ca mng v in tch (nn
gi l ho thm thu), nng lng ca qu trnh oxy ho tch lu li di dng u tin l mt
gradien nng H
+
v e.
Nhng t th hiu lm th no tch li ATP? Ngi ta thy rng cu trc hnh
nm ca mng c mt h thng H
+
translocase vn chuyn H
+
t mt ngoi mng vo trong
lm gim gradien nng H
+
, h thng ny c 2 yu t F
1
v F
0
, H
+
i qua yu t F
0
v F
1
.
Khi qua F
1
th to ra ATP t ADP v Pi. Mt cp H
+
qua h thng H
+
translocase cho ra 1
ATP v 1 cp e cho 3 ATP.
Vn to ra ATP khi H
+
qua h thng H
+
translocase nh th no? c hai gi thit:
Gi thit trc tip ca Peter Midchell: Theo thuyt ny khi cp H
+
i qua F
0
n tc ng
vo 1 oxy ca H
3
PO
4
to thnh H
2
O v gc phosphoryl cao nng ( P), F
1
c sn ADP n
s kt hp vi gc phosphoryl cao nng ny ( P) to thnh ATP (hnh 5.11).
Gi thit gin tip ca Boyer: Theo thyt ny vic vn chuyn H
+
t bn ngoi vo
khng c tc dng trc tip to ra ATP m n tc dng ln ATPase phn F
l
lm bin i cu
trc ca n lm cho ATP c sn c thot ra ngoi.
YU CU CN NM
CHNG V: TRAO I VT CHT V NNG LNG
Khi nim, ni dung ca trao i vt cht, kiu trao i vt cht. Khi nim v
trao i nng lng. Nng lng sng ca sinh vt. S h hp m bo. Qu trnh
photphoryl ho.
Cu 1: Khi nim v trao i vt cht ng vt? Cho bit s ca qu trnh ny?
Cu 2: Th no l kiu trao i vt cht ng vt? C s vt cht ca n?
Cu 3: Trnh by qu trnh oxy ho kh sinh hc ng vt (s h hp m bo)?
Cu 4: Trnh by qu trnh photphryl ho - oxi ho?
Cu 5: Nu vn tt cc qu trnh sinh ho ch yu to ATP m bo ng vt?
CHNG VI
GLUCID V QU TRNH CHUYN HO GLUCID
1. Khi nim v vai tr v glucid
Glucid l nhng hp cht hydratcacbon c cha nhm aldehyt hoc ceton cc
monosacarid hoc to thnh nhng cht nh vy khi b thu phn. L nhng cht ng bt,
cht x, l ngun dinh dng quan trng hng ngy ca mi c th sinh vt. Trong thc vt
glucid chim 80-90% vt cht kh, chng c to ra do qu trnh quang hp, c th ng vt
khng c kh nng ny m phi thu nhn trc tip glucid t thc vt. Glucid ch chim 2% vt
cht kh ca ng vt, nhng n ng vai tr quan trng
Vai tr: c hai vai tr ch yu ca glucid i vi ng vt l:
Vai tr v nng lng: 1 g glucid khi oxy ho hon ton cho 4,1 kcalo. i vi ngi
v gia sc ni chung glucid cung cp 60-70% nhu cu v nng lng cho c th, i vi loi
nhai li nh tru b d cu th hu ht nhu cu v nng lng l t glucid. Glucid l cht d
tr nng lng u tin (trc protein v lipid), l sn phm u tin ca qu trnh quang hp,
l ngun nng lng trc tip d dng khai thc v t gy bin c nguy hi cho c th.
Vai tr v to hnh:
T glucose c th chuyn ho thnh acid glucoronic l cht kh c s mt ca c th
T glucose c th amin ho thnh glucozamin hoc tip tc c acetyl ho thnh
acetyl glucozamin, y l 2 cht quan trong trong cu trc mng, n to ra yu t ch nh tnh
khng nguyn ca mng (v d mng ca hng cu).
Hnh 6.1. S chuyn ho ca Glucose thnh cc hp cht cu to
Acid hyalucoronic l cht "xi mng" c tc dng gn cc t bo vi nhau, khi cht ny
b phn hu th m bo b tan r, enzyme phn hu chng l hyalucoronidase (enzyme ny c
tnh c hiu theo loi).
Heparin l cht chng ng mu.
Cc ng ribose v desoxiribose l thnh phn cu to ca acid nucleic.
2. Phn loi
Glucid c phn loi thnh hai nhm ln: Monosaccharide (ose, ng n) v loi
ozid (loi a ng)
2.1. Monosaccharide (ose, ng n) l n v cu to ca glucid khng b thu phn
thnh cht n gin hn. Tu theo s carbon trong lin kt hydrocarbon m ngi ta phn
thnh cc nhm:
2.1.1. Triose: (C
3
H
6
O
3
). i din l glyxerose (glyxeraldehydeyt)
2.1.2. Tetrose: (C
4
H
8
O
4
). i din l erytrose, treose
O
C
C
CH
2
OH
OH H
H
O
C
C
C
OH H
H
D . Gl yx e r o se
CH
2
OH
OH H
O
C
C
C
H HO
H
CH
2
OH
OH H
D . e r yt r o se D . t r e o s e
2.1.3. Pentose: (C
5
H
10
O
5
). i din l ribose, desoxyribose, arabinose, xylose
O
C
C
C
H H
H
C
OH H
CH
2
OH
OH
H
O
C
C
C
OH H
H
C
OH H
CH
2
OH
OH
H
O
C
C
C
H HO
H
C
OH H
CH
2
OH
OH
H
O
C
C
C
OH H
H
C
H HO
CH
2
OH
OH
H
D.ribose D.desoxiribose
D.arabinose D.xylose
2.1.4. Hexose ((C
6
H
12
O
6
). i din l glucose, galactose, alose, manose
O
C
C
C
OH H
H
C
H HO
C
OH
H
CH
2
OH
OH H
O
C
C
C
OH H
H
C
OH H
C
H
HO
CH
2
OH
H HO
O
C
C
C
OH H
H
C
OH H
C
OH
H
CH
2
OH
OH H
O
C
C
C
H HO
H
C
H HO
C
OH
H
CH
2
OH
OH H
O
C
C
C
OH H
H
C
H HO
C
H
HO
CH
2
OH
OH H
D.alose D.glucose
D.manose
D.galactose
Ngoi nhng cht monose c nhm aldehydeyt k trn cn c loi monose cha nhm
ceton nh ribulose, fructose
CH
2
OH
C
C
O
C
H HO
C
OH
H
CH
2
OH
OH H
D.fructose
CH
2
OH
C
C
O
C
OH H
CH
2
OH
OH
H
D.ribose
2.2. Loi ozid (loi a ng): l nhng glucid phc tp do nhiu ng n ghp li. Loi ny
gm hai nhm ln l holozid v heterozid.
2.2.1. Holozid: l loi a ng khi thu phn cho ra ng n, nn cn gi l glucid
n thun. Nhm ny gm c:
Oligosaccarid (Oliose): c cu trc n gin gm t hai n ba ng n nn cn gi
l disaccarid, trisaccarid.
Polysaccarid (polyose): c cu trc phc tp gm nhiu ng n to thnh. Nhng
i din chnh l tinh bt, Glycogen, Cellulose, Hemicellulose...
2.2.2. Heterozid: l loi a ng khng thun nht, c cu to phn t v thnh phn
phc tp. Ngoi cc ng n cn c cc dn xut ca ng n nh Hexozamin,
Hexosunfat... i din nh mucopolysaccarid, cht in hnh nh acid hyaluronic. Loi ny
c trong dch bao khp, trong thu tinh th ca mt v trong nhiu m bo khc. Khi lng
phn t khong 200-500 ngn Dal, ho tan trong dung dch rt nht. Nh tnh ny nn acid
hyaluronic c v nh cht xi mng gn cc t bo trong m. em thu phn cht ny
ngi ta c acetyl glucozamin v acid glucoronic. Cng thc cu to nh sau:
COOH
O
CH
2
OH
NH CO CH
3
O
O
O
3. Tiu ho, hp thu v d tr glucid ng vt.
3.1. Tiu ho, hp thu tinh bt
Tinh bt l cht d tr glucid ca thc vt, c nhiu trong cc ht ng cc, cc loi c
nh khoai sn..., n l ngun nng lng chnh ca ng vt. Thnh phn ca tinh bt gm:
Amylose chim 20% khi lng tinh bt v Amylopectin chim 80% khi lng tinh bt.
Chng u c cu to t cc -D - glucose. Amylose cc phn t glucose lin kt vi
nhau bng lin kt -D - glucoside 1-4. Amylopectin ngoi lin kt -D - glucoside 1-4,
cc phn t ng cn lin kt vi nhau bng lin kt -D - glucoside 1-6, khong cch gia
cc lin kt glucoside 1-6 l t 20 n 25 phn t glucose. Cc phn t glucose trong
Amylose dng thuyn n to cho Amylose c dng xon l xo v to thnh phc mu xanh
vi iod nn iod l thuc th ca tinh bt.
Qu trnh tiu ho tinh bt l qu trnh thu phn bi enzyme glucozydase1-4
(Amylase) v glucozydase 1-6. C 4 loi glucozydase:
- Amylase: do tuyn nc bt v tuyn tu tit ra c tc dng ct lin kt glucoside 1-
4. di tc dng ca enzyme ny tinh bt b phn gii thnh maltose v cc dng dextrin.
- Amylase: c thc vt, trong cc ht ng cc lc ny mm, di tc dng ca
enzyme ny tinh bt b phn gii thnh maltose.
- Amylase: c ch yu gan v vi sinh vt, c tc dng ct lin kt glucoside 1-4, ct
tng phn t mt, sn phm ca n l glucose.
Glucozydase 1-6: c hot lc yu nc bt, mnh tuyn tu, n ct lin kt
glucoside 1-6.
ming: Tinh bt b tc dng c hc do b nhai, nho trn, trng n. Qu trnh ny
lm tng din tch tip xc gia enzyme vi c cht, ngoi ra tinh bt b - Amylase do tuyn
nc bt tit ra tc dng, enzyme ny cn c ion Ca
++
tham gia v c hot ho bi ion Cl
-
,
n hot ng trong mi trng gn trung tnh pH = 6,7 - 7,2. Di tc dng ca - Amylase
tinh bt b thu phn thnh ng maltose, v cc dng dextrin. Trong nc bt cn c
enzyme maltase thu phn maltose thnh glucose.
d dy: khng c enzyme tiu ho tinh bt, s tiu ho tinh bt b nh tr v mi
trng acid y do dch v lm t lit Amylase ca nc bt a xung. Song vi loi d
dy ln v n nhiu mt lc nh ln th phn tinh bt gia khi thc n vn b tiu ho do
HCl cha thm vo.
rut non: y l ni tiu ho kt thc tinh bt. Ngoi Amylase, glucozydase 1-6,
tuyn tu cn tit ra enzyme maltase, saccarase, lactase. Enzyme maltase thu phn ng
maltose, saccarase thu phn ng saccarose, lactase thu phn ng lactose. Di tc
dng ca cc enzyme k trn tinh bt v cc loi a ng khc bin thnh cc ng n
glucose, fructose, galactose.
Maltose +H
2
O ------------------> 2D-glucose
Maltase
Lactose +H
2
O -------------------> D-galactose +D-glucose
Lactase
Sacarose +H
2
O --------------------> D-fructose +D-glucose
Sacarase
Trehalose +H
2
O --------------------> 2D-glucose
Trehalase
T cc ng n , chng c hp thu qua t bo vch rut vo mu. Qu trnh hp
thu ng din ra theo 2 cch:
Hp thu th ng (theo s chnh lch v nng ), qu trnh ny khng tn nng lng.
Hp thu ch ng (ngc gradien nng ) qu trnh ny tiu tn nng lng ca ATP.
Tuy nhin c 2 cch u cn c vt mang, vt mang thng l protein.
Qu trnh hp thu ch ng thng gn lin vi h thng bm Na v K.
Khi cc ng n vo t bo vch rut, ti y chng c ng nht ho thnh
glucose, nh enzyme isomerase. Glucose qua t bo vch rut vo mao mch v h tnh mch,
qua tnh mch ca v gan, tu theo yu cu m glucose s bin thnh fructose,
galactose... gan glucose t thc n vo c s l theo 2 hng:
Phn ln theo hng chuyn ho thnh lipid, mt phn chuyn ho thnh glycogen
d tr
S dng vo cc nhu cu nh nng lng, to thnh cc hp cht cu to... Qu trnh s
dng, glucose c th vo mu ch ti cc m bo.
3.2. Sinh tng hp glycogen
Cu to ca glycogen: Glycogen l cht d tr glucid ca ng vt, c th coi
glycogen nh l "tinh bt" ca ng vt, v n cng gm 2 lin kt -D 1-4 v -D 1-6
glucoside, nhng n khc tinh bt ch l s r nhnh rm rp hn, c cch 8-10 phn t
glucase c mt lin kt nhnh -D 1-6. Glycogen c nhiu gan ( chim 5-7% khi lng
ca gan) c n chim 2% khi lng ca c, do khi lng c l ln nn glycogen c c
l chnh. Hm lng ny c th bin ng ph thuc vo dinh dng v trng thi sinh l
(i, no, lao ng, ng, thc...)
gan, c v nhiu m bo khc c h thng enzyme chuyn ho glucose thnh
glycogen. Trong t bo h thng enzyme phn b t bo cht v qu trnh sinh tng hp
glycogen din ra t bo cht. Di tc dng ca cc enzyme hexokinase, mutase v
transglucozydase mt lot cc phn ng din ra nh sau:
1/ Hot ho glucose do tc dng ca gluco-kinase
2/ ng phn ho di tc dng ca enzyme mutase
O
CH
2
-O-P
O
CH
2
-OH
O-P
Gluco 6-P
Mutase
Gluco-1-P
3/ Hot ho Glucose vi UTP
O
H OH
H H
H H
H
2
C O P O
O-
O
P
O-
O
P -O
O-
O
P O
O-
O
P -O
O-
O
P -O
O-
O
O
CH
2
-OH
O-P
O
NH
O N
UTP
Gluco-1-P
+

4/ To Amylose: Di tc dng ca enzyme glycogensyntetase (hay trans glucozydase
1-4) n phn t UDP- glucose lin kt vi nhau theo lin kt 1-4 glucoside to thnh chui
amylose.
5/ To Glycogen: Di tc dng ca enzyme transglucozydase 1-6, chui Amylose c
cch 8-10 phn t glucose s c lin kt 1-4 chuyn thnh lin kt 1-6. Kt qu to thnh phn
t glycogen c nhnh r rm rp, cc phn t ny tch t li trong t bo thnh ht.
Enzyme trans glucozydase 1- 4 tn ti 2 trng thi:
Dng I: Independant (c lp, t ch) trng thi ny c hot lc.
Dng D: Dependant (ph thuc) khng c hot lc. Hai dng ny c th chuyn ho cho
nhau, t dng I nu c phosphoryl ho th s chuyn thnh dng D v ngc li. iu khin
qu trnh ny l hormone Insuline ca tuyn tu. Hormone ny c vai tr chuyn ho enzyme
ny t dng D sang dng I lm tng cng qu trnh tng hp glycogen t lm gim hm
lng ng trong mu.
+ ATP
Dng I < ===== > Dng D
- ATP
3.3. S phn gii glycogen
Khi nhu cu v nng lng ca c th tng ln, lng glucose s b huy ng v hm
lng ca n trong mu b h xung, lc gan s gii phng glucose t glycogen a
vo mu, gi cho hm lng glucose trong mu c n nh. Qu trnh phn gii glycogen
c cng xy ra nhng n ch chuyn ho n dng glucose 6-P ri a vo qu trnh s dng
ch khng thnh glucose t do a vo mu.
Glycogen gan c phn gii theo 2 cch:
Cch 1: Phn gii theo con ng thu phn bi tc dng ca enzyme - Amylase vi
s tham gia ca nc, cch phn gii ny khng ng k.
Cch 2: Phn gii theo con ng phosphoryl ho (phosphorolysis: phospho phn),
cch phn gii ny l ch yu.
Qu trnh ny c thc hin bi mt h thng enzyme m ch yu l enzyme
phosphorylase "a". Di tc dng ca enzyme ny qu trnh phn gii din ra nh sau:
phosphorylase "a" mutase phosphatease
Gly + H
3
PO
4
----------------------> Gl 1-P ----------> Gl 6-P ----------------- > Gl + H
3
PO
4
Glucose c tch khi cc nhnh ca glycogen qua hot ng ca 2 enzyme: glycogen
phosphorylase v phosphoglucomutase. Glycogen phosphorylase xc tc phn ng ct lin
kt ion -1-4 glucoside. 2 gc glucose trong glycogen di s tn cng bi phosphate v c,
tch gc glucose cui cng to thnh -D- glucose 1- phosphate (hnh 6.2). Phn ng
phospho phn ny xy ra s huy ng bn trong t bo ca glycogen d tr, khc vi s thu
phn lin kt glucoside bi amylase khi thoi ha glycogen. Trong phospho phn, mt s
nng lng ca lin kt glucoside c gi trong s hnh thnh este phosphate, glucose 1-
phosphate.
Pyridoxal phosphate l yu t cn thit trong phn ng
glycogen phosphorylase; nhm phosphate ca n hot ng
nh l s xc tc acid chung, lm tng s tn cng bi Pi trn
lin kt glucoside. Hon ton khc vai tr ca yu t pyridoxal
phosphate trong trao i acid amin.
Glycogen phosphorylase tn cng lp li trn cc u
khng kh ca cc nhnh glycogen n im cn 4 gc
glucose ca im nhnh (1-6). y s ngng hot ng ca
glycogen phosphorylase. S thoi ha tip tc c th xy ra.
Glycogen b b gy gn cc im nhnh ( -1- 6) sau khi loi cc gc glucose u
khng kh bi glycogen phosphorylase (hnh 6.2). Cc gc glucose gn nhnh c loi b
tip bc hai nh hot ng ca enzyme loi nhnh. u tin hot tnh transferase ca
enzyme thay i v tr cn tr ca 3 gc glucose k t nhnh gn u khng kh, chng c
tn cng li trong lin kt (1- 4). Sau gc glucose n l c loi ra bi hot ng
enzyme (1-6) glucosidase. Ch sau khi hot ng ca enzyme loi nhnh oligo ( 1-6) n
Hnh 6.2: Loi gc glucose u cui khng kh ca chui glycogen bi hot ng
ca glycogen phosphorylase. Qu trnh ny c lp i lp li, kt qu l loi gc
glucose cho n khi cn 4 gc glucose tnh t im nhnh ( hnh 6.3).
( 1-4) glucotransferase, n xc tc cho 2 phn ng loi nhnh glucose-1-phosphate, sn
phm cui ca phn ng glycogen phosphorylase s c bin i thnh glucose-6-
phosphate bi phosphoglucomutase, y l phn ng thun nghch.
Glucose-1-phosphate glucose 6-phosphate
Phosphoglucomutase i hi yu t glucose 1,6-diphosphate, vai tr ca n tng t
nh 2,3-diphosphoglycerate trong phn ng xc tc bi phosphoglycerate mutase (hnh 6.2).
Phosphoglucomutase ging phosphoglycerate mutase, chu trnh gia dng phosphoryl ha v
khng phosphoryl ha. Tuy nhin trong phopshoglucomutase nhm hydroxyl ca gc Ser
trong trung tm hot ng thc hin phosphoryl ha trong vng xc tc.
Enzyme phosphorylase tn ti 2 trng thi:
Trng thi hot ho (phosphorylase "a") trng thi ny n tn ti cu trc bc 4 gm
4 tiu phn (tetrame).
Trng thi c ch (phosphorylase "b") trng thi ny n tn ti cu trc 2 tiu phn
(dime). Hai trng thi ny c th chuyn ho cho nhau, t dng "b" nu c phosphoryl ho
th s chuyn thnh dng "a" v ngc li.
Hnh 6.3: Glycogen b b gy gn cc im nhnh -1- 6

Protein kinase li chu s tc dng ca 3
/
,5
/
- AMP vng di s iu tit ca Adrenalin
v glucagon.
3.4. S tiu ho v hp thu cht x
Cht x bao gm nhiu nhm, trong ch yu l cellulose v hemicellulose, ngoi ra
cn c lignin (v bc t bo). T l cc loi ny khc nhau cc loi rau c v tui ca
chng. Loi c non hemi cellulose chim 30-40%, cellulose chim 60-70%. Khi c gi
cellulose chim 90% cn hemi cellulose ch chim 5-10%.
V cu to: cellulose c cu to t -glucose, cc phn t - glucose lin kt vi nhau
bng lin kt - glucosid 1-4. Cc phn t -glucose trong cellulose dng gh lm cho
cellulose c cu trc hnh si.
O
CH
2
OH
O
O
CH
2
HO
O
CH
2
O
n
Hemicellulose l cht c cu to t cc ng n khng phi glucose nh: pentose,
hexose loi manose, galactose, fructose,...
CHO
C
C
C
C
CH
2
-OH
H OH
OH
H
OH H
OH
H
CHO
C
C
C
C
CH
2
-OH
OH H
OH
OH
OH H
OH
H
CH
2
-OH
C
C
C
C
CH
2
-OH
O
OH
H
OH H
OH
H
Galactose
Fructose
Manose
Lignin: l hp cht phc tp, thnh phn ch yu l cc acid xut pht t ng, n
khng tiu ho c.
Cht x, bn thn ng vt khng th tiu ho c v chng khng tit ra enzyme tiu
ho cht x (enzyme cellulase). Nhng trong qu trnh tin ho ca sinh vt, phn ln ng
vt n c nh tru, b, d, cu, th, ngng... hnh thnh mt kh nng thch nghi, l s
cng sinh gia chng vi vi sinh vt (VSV), ch c VSV mi c enzyme tiu ho cht x
(enzyme cellulase). S cng sinh ny c tin hnh ng tiu ho m in hnh l d c loi
nhai li, manh trng nga, th, ngng....
S tiu ho cht x d c
Trong qu trnh tin ho, d c khng ch l ni cha thc n, m d c cn tham gia rt
tch cc vo qu trnh tiu ho, c th coi d c l mt ti ln men cht x. Qu trnh theo
s sau:
Cellulase (VSV) Isomelase(VSV) ln men (VSV)
Cellulose -------------> -glucose <=========> -glucose ------------> cc acid bo bay hi
Cc acid bo bay hi l sn phm ca qu trnh ln men, y l ngun nng lng chnh
cho loi nhai li (chim 60-80% nhu cu v nng lng ca loi nhai li). Qu trnh tiu ho
ny c thc hin bi h VSV trong d c.
H VSV trong d c
V s lng l rt ln: nhm vi khun (Bacteria) c ti 10
9
con/gam cht cha d c,
nhm nguyn sinh ng vt (Protozoa) c ti 10
5
- 10
6
con/gam cht cha d c.
V chng loi chia lm 3 lp ln:
Vi khun (Bacteria) bao gm: Trc khun (Bacteria bacillus); Cu khun (Coccus);
Xon khun( Spirochera). Vi khun chim s lng ln nht trong h VSV d c, phn ln
chng l cc VSV k kh, l nhm ng vai tr chnh trong tiu ho d c, chng c tc
dng phn gii cellulose thnh cc acid bo bay hi.
Nhm nguyn sinh ng vt (Protozoa): nhm ny cng c hng trm chng loi khc
nhau, c tc dng phn gii cellulose v ng bt thnh cc dng ng d tiu, tch lu
Hnh 6.4. Cu to ca tho phc trng (protozoa)
trong t bo (hnh 6.4). Nhc im ca nhm ny l chng khng c kh nng s dng NH
3
nh vi khun, ngun nit p ng nhu cu ca chng ch yu l t thc n v vi khun nn
chng nut rt nhiu vi khun, c nhiu quan im cho rng nu c ch nhm ny s lm tng
qu trnh ln men xellolose do vi khun khng b dit.
Nm (Fungi): bao gm nm men v nm mc. Ngi ta cho rng nm c vai tr xm
nhp v tiu ho thnh phn cu trc t bo thc vt, lm gim bn cht ca cu trc ny
gp phn lm tng s ph v ca cc mnh thc n khi c nhai li, t to iu kin cho
vi khun bm vo phn gii cellulose. Mt s nm men c th ln men ng glucose,
chuyn ho chng thnh CO
2
v H
2
O v tng hp thnh nhiu loi vitamin nhm B.
Di tc dng ca h VSV d c, cht x b phn gii thnh - glucose. - glucose i
theo 2 hng:
Tch lu thnh glycogen trong protozoa, y l con ng ph.
Ln men l con ng ch yu. Ln men l qu trnh phn gii glucose mt cch phc
tp din ra trong iu kin ym kh. Qu trnh ny din ra trong t bo VSV. Trong qu trnh
ny phn t ng glucose bin thnh cc acid bo bay hi. i vi bn thn t bo VSV y
l cch khai thc nng lng sng, qu trnh ln men l qu trnh to ATP cho VSV, cn
cc acid bo bay hi l sn phm thi loi ca VSV sau khi dng glucose. Nhng acid bo
ny l nhng cht dinh dng ht sc quyt nh i vi ng vt nhai li sau khi c hp
thu vo mu.
T l v hm lng cc acid bo bay hi ph thuc vo hot ng ca VSV, m s hot
ng ny li ph thuc vo ngun thc n v pH ca d c. Trong iu kin ti u: pH d c
bng 6-7 th nhng chng VSV ln men acid axetic l ch yu, hm lng acid ny l 60%,
ri n acid propionic: 20%, acid butylic: 10%, acid valeic: 5% v acid lactic l rt t.
Yu t lm cho pH ca d c n nh l nh cc mui bicacbonat ca nc bt ca loi
nhai li (nc bt loi nhai li c hm lng bicacbonat rt cao, lng nc bt tit ra li
nhiu (100lit/ngy m). Cc bicabonat vo d c lm trung ho acid bo to ra trong qu
trnh ln men:
NaHCO
3
+ H
+
--------- > Na
+
+ H
2
CO
3
---- > H
2
O + CO
2
Nh vy lng CO
2
sinh ra kh nhiu, v l do no m khng c CO
2
ra kp th
s sinh ra chng chng hi d c.
D c hay nhng xoang tiu ho nh vy l ni l tng cho h VSV hot ng v
c cc iu kin ti u l:
Nhit : 38-39
o
C
Ym kh.
m: 45-65% ( m ny do nc ung v nc bt ).
pH thch hp: 6,5-7,5. pH ny c th thay i do nhiu yu t nht l do thc n: nu n
thc n d tiu th qu trnh ln men mnh, lng acid bo tng ln pH s gim, n thc n
chua pH cng gim, thc n nhiu protein pH s tng... Khi pH thay i do thc n th t l
cc acid bo bay hi s thay i v ko theo s thay i pH cng mnh. Nu acid lactic tng
ln s sinh ra a chy, acid butyric tng s sinh ra th ceton huyt...
Cc acid bo c hnh thnh d c, chng thm qua vch d c vo mu v c s
dng trc tip vo qu trnh dinh dng ca loi nhai li nh cung cp nng lng, tng hp
cc acid amin, tng hp lipid sa v mt phn tr thnh glucose gan.
4. S chuyn ho trung gian ca glucose
4.1. Khi qut v s chuyn ho trung gian ca glucose
Glucose c mu ch ti cc m bo v c a vo t bo nh h thng vn chuyn
tch cc. t bo cht glucose c phn gii dng vo cc nhu cu ca t bo m trc
ht l nhu cu v nng lng. Trong c th ni s dng glucose nhiu nht l c bp.
Xt v mt chuyn ho glucose c th sinh vt c hai kiu: Phn gii ym kh v phn
gii hiu kh. Hai cch phn gii ny c bit cht ch VSV. VSV phn gii ym kh khi c
O
2
th khng sng c, nu l hiu kh th thiu O
2
cng khng sng c. Gia hai gii
c mt gii trung gian dng c c hai cch phn gii trn l m bo ng vt.
VSV s phn gii ym kh glucose gi l s ln men, cn m bo ng vt gi l s
ng phn. Hai qu trnh ging nhau ch l u phn gii glucose trong iu kin ym
kh v u khai thc nng lng to ATP cho t bo, n khc nhau ch l s ln men din ra
trong t bo VSV, sn phm cui cng l nhng sn phm ln men nh ru ethylic (ln men
ru), acid axetic (ln men dm), acid lactic (ln men sa chua)... cn qu trnh ng phn
ch cho ra mt sn phm duy nht l acid lactic:
C
6
H
12
O
6
--------> 2 C
3
H
6
O
3
+ Q
4.2. Cch phn gii ym kh glucose m bo ng vt - Qu trnh ng phn
(glycolysis)
Trong qu trnh ng phn (glycolysis - ting Hylp glykys ngha l ngt v lysis
ngha l phn tch) phn t glucose c phn gii trong cc phn ng xc tc bi enzyme
thnh 2 phn t pyruvate ri chuyn thnh 2 phn t acid lactic km theo nng lng c
gii phng dng ATP. Cho n nay qa trnh ng phn c nghin cu k lng.
S pht hin u tin ca Eduard Buchner (nm 1897) v s ln men nh dch chit ca
t bo nm men, cc nghin cu chi tit bi Fridz Lipmann v Herman Kalekar (nm 1941)
v vai tr trao i cht ca cc hp cht cao nng nh ATP trong qu trnh trao i. Cc phn
ng ca qu trnh ln men v ng phn trong dch chit ca nm men v c l trung tm
nghin cu ha sinh v cc enzyme tham gia xc tc cc qu trnh ny cng nghin cu k lng.
Trong c th ng vt c iu kin ym kh xy ra qu trnh ng phn, l
nhng m bo mch mu b chn p, mu khng lu thng ti, nht l nhng lc lao ng,
iu kin ym kh cng tng v qu trnh ng phn din ra cng mnh.
4.2.1. Qu trnh ng phn gm 2 pha.
B gy glucose 6 carbon thnh 2 phn t pyruvate 3 carbon xy ra trong 10 bc, 5
bc u c gi l pha chun b (hnh 6.5a). Trong cc phn ng ny, glucose u tin b
phosphoryl ho nhm Hydroxyl C-6 (bcO). D-glucose-6-phosphate sau to thnh D-
fructose-6-phosphate (bc O), tip tc b phosphoryl ha, ln ny l C-1, to thnh
fructose-1,6-diphosphate (bcO). i vi c 2 ln phosphoryl ha, ATP l cht cho
phosphate.
Fructose-1,6-diphosphate tip tc to thnh 2 phn t 3 carbon, dihydroxyacetone
phosphate v glyceraldehyde-3-phosphate (bcO). Dihydroxylacetone phosphate c ng
phn ha thnh phn t glyceraldehyde 3- phosphate th 2 (bcO), y l bc cui cng
trong pha u tin ca qu trnh ng phn. Nh vy pha ny s dng 2 phn t ATP
hot ha phn t glucose v ct thnh 2 phn t 3 carbon.
Hnh 6.5. Hai pha ca quy trnh ng phn..
Nng lng tr li trong pha hon tr ca qu trnh ng phn (hnh 6.5): Mi phn t
glyceraldehyde- 3- phosphate b oxy ha v b phosphoryl ha bi phosphate v c (khng
bi ATP) to thnh 1,3-diphosphoglycerate (bcO). Nng lng c gii phng cng nh
2 phn t 1,3- diphosphoglycerate hnh thnh 2 phn t pyruvate (bcO v bc n G).
Nng lng ny c thc hin bi cp phosphoryl ha ca 4 phn t ADP thnh ATP, tr i
2 phn t ATP c s dng trong pha chun b. Nng lng ca pha hon tr to thnh 2
phn t NADH
2
trn mt phn t glucose.
Trong cc phn ng lin tc ca qu trnh ng phn, ba loi bin i ha hc ng
lu c bit: (1) s thoi ha ca b khung carbon ca glucose thnh pyruvate, (2) s
phosphoryl ha ca ADP thnh ATP bi hp cht phosphate nng lng cao to trong qu
trnh ng phn, v (3) s chuyn cc nguyn t hydro hoc cc in t n NAD
+
to
thnh NADH
2
. S phn gii sn phm pyruvate ph thuc vo loi t bo v cc trng hp
trao i cht.
Phn gii pyruvate: C 3 hng trao i ca pyruvate c to thnh bi qu trnh
ng phn. Trong cc m hoc c th hiu kh th qu trnh ng phn tip tc ch bc
u trong s thoi ha ca glucose (hnh 6.6). Pyruvate c oxy ha, mt mt nhm CO
2
,
to thnh nhm acetyl ca acetyl CoA. Sau oxy ha phc cht n CO
2
v H
2
O qua mt
chui phn ng ca chu trnh Krebs (Chu trnh acid xitric) xy ra trong ty th. Nng lng t
cc phn ng chuyn in t dn n tng hp ATP trong ty th.
Hnh 6.6: Ba kh
nng phn gii trao i
cht ca pyruvate c
to thnh trong pha hon
tr ca qu trnh ng
phn. Pyruvate cng l
cht tin thn trong nhiu
phn ng ym kh.
Con ng th hai
i vi s trao i pyruvate
l s kh n thnh lactate.
Khi m c, xng co c
mnh phi lm vic trong
iu kin ym kh,
pyruvate khng th b oxy
ha v thiu oxy. Di iu
kin , pyruvate b kh
thnh lactate. Chc chn
cc m v cc loi t bo
(vng mc, no, hng cu)
c s bin i glucose
thnh lactate thm ch di
iu kin hiu kh. Lactate cng l sn phm ca qu trnh ng phn di iu kin ym
kh trong vi sinh vt khi xy ra s ln men acid lactic (hnh 6.6).
Con ng th 3 i vi s trao i ca pyruvate dn n to ethanol. Trong mt s
m thc vt v trong ng vt khng xng sng, sinh vt n bo v vi sinh vt nh nm
men bia, pyruvate c bin i ym kh to thnh ethanol v CO
2
, qu trnh ny c gi l
s ln men ru (alcohol) hay ethanol (hnh 6.6)
4.2.2. Pha chun b ca qu trnh ng phn cn ATP.
Pha ny xy ra 5 phn ng:
1. S phosphoryl ha ca glucose.
Trong bc u tin ca qu trnh ng phn glucose c phosphoryl ha C-6
thnh glucose-6-phosphate. ATP l cht cho phosphate (Hnh 6.7).

Phn ng ny xy ra trong t bo v c xc tc bi hexokinase. Tn chung kinase
c s dng cho cc enzyme xc tc chuyn nhm phosphate cui cng t ATP n mt s
cht nhn hexose, trong trng hp ca hexokinase cc kinase nm trong lp transferase.
Hexokinase xc tc s phosphoryl ha khng ch ca D-glucose m cn ca cc
hexokinase khc, nh D-fructose v D-mannose. Hexokinase. Cng ging nh nhiu kinase
khc n cn Mg
2+
cho s hot ng, v c cht thc s ca enzyme khng phi l ATP
4-
m
l phc hp MgATP
2-
(xem hnh 6.8).

Hnh 6.7. Phosphoryl ho glucose
Hnh 6.8: S to thnh phc hp
Mg
2+
Hexokinase c mt trong cc t bo
ca tt c cc loi. T bo gan cng c
dng hexokinase gi l hexokinaseD
hoc glucokinase. Cc hexokinase khc
nhau trong ng hc v cc c tnh
iu ho.
2. S bin i ca glucose - 6- phosphate thnh fructose-6-phosphate.
Phosphohexose isomerase (phosphoglucose isomerase) xc tc s ng phn ha ca
aldolase, glucose - 6 - phosphate thnh fructose 6- phosphate(hnh 6.9).
Hnh 6. 9. ng phn ho glucose 6 - phosphate
y l phn ng thun nghch nn s thay i nng lng t do nh. Phosphohexose
isomerase cng cn Mg
2+
v c bit cho glucose 6-phosphate.
3. S phosphoryl ho fructose 6-phosphate thnh fructose 1,6-diphosphate
Hnh 6.10. phosphoryl ho fructose 6- phosphate
y l phn ng th 2 quan trng ca qu trnh ng phn, phosphofructokinase-1 xc
tc chuyn nhm phosphate t ATP n fructose 6- phosphate thnh fructose-1,6-diphosphate
(hnh 6.10).
Phn ng ny l khng thun nghch di cc iu kin t bo. Enyme xc tc c gi
l phosphofructokinase 1 (PRK-1) phn bit n vi enzyme th 2 (PFK-2) xc tc cho s to
thnh fructose 2,6-diphosphate t fructose 6-phosphate.
Trong mt s vi khun v vi sinh vt n bo v trong c thc vt, c
phosphofructokinase s dng pyrophosphate (PPi) m khng s dng ATP nh l cht cho
nhm phosphate trong s tng hp ca fructose 1,6 diphosphate.
Fructose-6-phosphate + PPi
+ 2
Mg
Fructose-1,6-diphosphate + Pi (
' 0
G = -
14KJ/mol)
Phosphofructokinase 1 ging hexokinase l enzyme iu ho, n l im chnh ca s
iu ho trong qu trnh ng phn. Hot tnh ca PFK-1 tng khi s cung cp ATP ca t
bo suy gim hoc khi c s vt tri ca cc sn phm ATP b b gy nh ADP v AMP.
Enzyme c ch mi khi t bo c nhiu ATP v khi n c cung cp tt bi cc nhin liu
khc nh acid bo. Fructose 2,6-diphosphate, tng t cu trc i vi sn phm ca phn
ng ny, nhng khng phi l cht trung gian trong qu trnh ng phn, m l cht kch
thch c hiu lc ca c hai enzyme ph thuc ATP v ph thuc PPi.
4. Ct fructose 1,6- diphosphate
Enzyme fructose-1,6-diphosphate aldolase thng c gi n gin l aldolase, xc
tc tr li s ngng t aldol. Fructose-1,6- diphosphate c ct thnh 2 triose phosphate
khc nhau l glyceraldehyde 3- phosphate v dihydroxyacetone phosphate (hnh 6.11)
Hnh 6.11. Ct Fructose 1,6- diphosphate
Aldolase ca m ng vt c xng sng khng i hi cation ha tr hai, nhng trong
nhiu vi sinh vt aldolase l enzyme c Zn
2+
. Mc du phn ng aldose c s thay i nng
lng t do chun ln trong hng ct, trong cc t bo n c th tin hnh nhanh chng theo
cc hng khc nhau. Trong sut qu trnh ng phn cc sn phm phn ng (2 triose
phosphate) c di chuyn nhanh bi bc 2 tip theo, phn ng hng theo chiu ct.
5. S chuyn ha ln nhau ca cc triose phosphate.
Ch mt trong 2 triose phosphate c to thnh l aldose glyceral dehyde3-phosphate
c th c bin i vi cc bc phn ng tip ca qu trnh ng phn. Tuy nhin,
dihydroxy acetone phosphate li nhanh chng bin i thnh glyceraldehyde-3-phosphate bi
enzyme th 5 ca qu trnh ng phn, triose phosphate isomerase (hnh 6.12). Phn ng
ny kt thc pha chun b ca qu trnh ng phn, trong phn t hexose b phosphoryl
ha v tr C-1 v C-6 v sau to thnh 2 phn t glyceral dehyde-3-phosphate. Cc
hexose khc nh D- fructose, D-manose v D-galactose cng bin i thnh glyceral dehyde
3- phosphate.
Hnh 6.12. S chuyn ha ln nhau ca cc triose phosphate
4.2.3. Pha hon tr ca qu trnh ng phn to ATP.
Pha hon tr ca qu trnh ng phn bao gm s bin i nng lng cc bc
phosphoryl ha trong mt s nng lng t do ca phn t glucose b bin i to thnh
ATP. Cn nh rng mt phn t glucose to thnh 2 phn t glyceral dehyde-3 phosphate. C
2 phn t ny sau i vo pha th 2 ca qu trnh ng phn. S bin i 2 phn t
glyceral dehyde -3 phosphate thnh 2 phn t pyruvate km theo s to thnh 4 phn t ATP
t ADP. V c 2 phn t ATP c s dng trong pha chun b ca qu trnh ng phn
phosphoryl ha 2 u cui ca phn t hexose.
6. S oxy ha glyceral dehyde-3- phosphate thnh 1,3 disphospho glycerate.
Giai on u trong pha hon tr ca qu trnh ng phn l s oxy ho, s bin i
Hnh 6.13. S oxy ho glyceral dehyde-3- phosphate
glyceral dehyde-3- phosphate thnh 1,3 diphosphate glycerate c xc tc bi glyceral
dehyde-3 phosphate dehydrogenase (hnh 6.13). y l phn ng u tin ca cc phn ng
bin i nng lng ca qu trnh ng phn dn n s hnh thnh ATP. Nhm aldehyde
ca glyceraldehyde 3- phosphate c dehydrogenase ha, khng to thnh nhm carboxyl t
do m to thnh acid carboxylic anhydride vi acid phosphoric. Loi ny ca anhydride c
gi l acyl phosphate c nng lng t do chun rt cao khi thu phn (
' 0
G = -49,3 KJ/ mol).
Rt nhiu nng lng t do ca s oxy ha nhm aldehyde ca glyceraldehyde-3-phosphate
c bin i bi s to thnh ca nhm acyl phosphate C-1 ca 1,3-diphosphate glyxerate.
Hnh 6.14: (a) M t chi tit phn ng glyceraldehyde-3-phosphate dehydrogenase. Trong
bc (1) to thnh lin kt ha tr thiohemiacetal gia c cht v nhm sulfhydryl ca gc cys trong
trung tm hot ng ca enzyme. Cht trung gian c cht ny b oxy ha bi NAD
+
(bc (2) bin i
n thnh cht trung gian lin kt ha tr acyl-enzyme, thioester. (bc (3)) Lin kt gia nhm acyl v
nhm thiol ca enzyme. Trong bc (4) lin kt thioester tri qua phn ng phn ly acid phosphoric
(tn cng bi Pi), gii phng enzyme t do v to thnh acyl phosphate (1,3-diphosphate glyceral) (b)
Iodoacetate l cht c ch c hiu qu ca glyceraldehyde -3- phosphate dehydrogenase v n to
thnh lin kt cng ha tr vi nhm -SH ch yu ca trung tm hot ng enzyme, lm n bt hot.
Cht nhn hydrogen trong phn ng glyceraldehyde-3-phosphate dehydrogenase l
coenzyme NAD
+
, dng oxy ha ca nicotinamide adenine dinucleotide. S kh NAD
+
c
tin hnh bi enzyme chuyn ion hydrro (:H
-
) t nhm aldehyde ca glyceral dehyde 3
phosphate n chu trnh nicotinamide ca NAD
+
to thnh coenzyme dng kh. Nguyn t
hydro khc ca phn t c cht xut hin trong dung dch nh H
+
(hnh 6.14 a).
S oxy ha glyceral dehyde-3-phosphate bao gm sn phm trung gian trong c cht
l lin kt cng ha tr vi enzyme (hnh 6.14a). Nhm aldehyde ca glyceral dehyde-3-
phosphate phn ng u tin vi nhm SH ca Cys ch yu trong trung tm hot ng ca
enzyme. Phn ng ny tng ng vi s to thnh ca hemiacetal nhng trong trng hp
ny sn phm l thiohemiacetal. S pht hin ra glyceral dehyde-3-phosphate dehydrogenase
b c ch bi iodoacetate (hnh 6.14 b) l rt quan trng trong lch s nghin cu qu trnh
ng phn.
NADH
2
to thnh trong bc ny ca qu trnh ng phn phi c oxy ha li thnh
NAD
+
. Cc t bo c s lng gii hn NAD
+
v qu trnh ng phn c th thiu n mt
na NAD
+
l do NADH
2
khng c oxy ha tr li. Cc phn ng trong NAD
+
c
phc hi ym kh s c miu t chi tit sau.
7. Chuyn phosphate t 1,3 diphosphoglycerate n ADP.
Enzyme phosphoglycerat kinase chuyn gc phosphate nng lng cao t nhm
carboxyl ca 1,3 diphosphoglycerate n ADP, to thnh ATP v phosphoglycerate (hnh
6.15).
Hnh 6.15. To ATP t 1,3 diphosphoglycerate
8. S bin i ca 3-phosphoglycerate thnh 2-phosphoglycerate.
Enzyme phosphoglycerate mutase xc tc chuyn thun nghch nhm phosphate gia
C-2 v C-3 ca glycerate Mg
2+
(hnh 6.16).

9. S loi nc ca 2-phosphoglycerate thnh phoshoenolpyruvate.
Phn ng ng phn th hai to ra hp cht vi kh nng chuyn nhm phosphate
mc cao c xc tc bi enolase. Enzyme ny lm tng kh nng loi phn t nc ca
phosphoglycerate to thnh phosphoenolpyruvate (hnh 6.17)
10. Chuyn gc phosphate t phosphoenolpyruvate n ADP.
Bc cui cng trong qu trnh ng phn l chuyn gc phosphate t
phosphoenolpyruvate n ADP, xc tc bi pyruvate kinase (hnh 6.18).
Hnh 6.18. To ATP t phosphoenolpyruvate
Trong phn ng ny, s phosphoryl ha c cht - sn phm pyruvate xut hin u tin
dng enol. Dng enol nhanh chng h bin v khng tn ti m to thnh dng ceto ca
Hnh 6.17. To phosphoenolpyruvate
Hnh 6.16. To 2-phosphoglycerate
pyruvate, dng ny chim u th pH7. Phn ng pyruvate kinase v c bn khng thun
nghch di iu kin ni bo. Pyruvate kinase i hi c K
+
v Mg
2+
hoc Mn
2+
. N gi v
tr quan trng ca s iu ho (hnh 6.19).

Hnh 6.19. S h bin ca pyruvate
4.2.4. S cn bng tng th v lm tng ATP
Chng ta c th xy dng s cn bng i vi qu trnh ng phn tnh ton cho (1)
s phn khung carbon ca glucose, (2) s i vo ca Pi v NAD
+
v s i ra ca ATP v (3)
con ng ca cc in t trong cc phn ng oxy ha kh pha tay tri ca s cn bng gii
thiu tt c s i vo ca ATP, NAD
+
, ADP v Pi (tham kho hnh 6.5) v pha tay phi gii
thiu tt c s i ra (cn lu rng mi phn t glucose to thnh 2 phn t glyceral dehyde-
3-phosphate):
Qu trnh ng phn c iu ho cht ch.
Khi nghin cu s ln men ca glucose bi nm men, Louis Pasteus pht hin ra
rng c tc v tng s glucose tiu th tng ln nhiu ln di iu kin k kh. Nhng
nghin cu sau c cho thy chnh s khc nhau ln v tc ca qu trnh ng phn
di iu kin k kh v hiu kh l c s ha sinh ca hiu ng Pasteus.
S to thnh ATP t qu trnh ng phn di iu kin k kh (2ATP vi mt phn
t glucose) l nh hn nhiu khi oxy ha phn t glucose n CO
2
di iu kin hiu kh (38
hoc 39 ATP cho mt phn t glucose). Nh vy, khong 19 ln glucose nhiu hn b tiu th
iu kin k kh so vi hiu kh to thnh cng lng ATP.
S bin i lin tc ca glucose qua con ng ng phn c iu ho thc hin
hng s mc ATP (p ng yu cu ca cc hp cht trung gian ca ng phn phc v
vai tr sinh tng hp). S yu cu iu chnh tc qu trnh ng phn c thc hin bi
s iu ho ca 2 enzyme ng phn: phosphofructokinase-1 v pyruvate kinase. C 2
enzyme c iu ho allosteric giao ng tng giy trong s cn bng ca t bo gia s to
thnh v s tiu th ATP.
Glucose + 2ATP + 2NAD + 4ADP+ 2Pi 2pyruvate + 2ADP + 2H
+
+ 4ATP + 2H
2
O
Nu cn bng 2 pha, chng ta nhn c cn bng tng th i vi qu trnh ng
phn di cc iu kin hiu kh.
Glucose + 2NAD
+
+ 2ADP + 2Pi 2 pyruvate + 2NADH
2
+ 2H
+
+ 2ATP + 2H
2
O
Hai phn t NADH
2
to thnh bi qu trnh ng phn trong t bo l iu kin hiu
kh ti oxy ha thnh NAD
+
bi s chuyn in t ca chng n chui h hp, m trong cc
t bo nhn chun l ty th. y cc in t cui cng c chuyn n O
2
.
2NADH
2
+ 2H
+
+O
2
2NAD
+
+ 2H
2
O
in t chuyn t NADH
2
n O
2
trong ty th cung cp nng lng cho tng hp ATP
bi s phosphoryl ha trongchui h hp.
Tng th ca qu trnh mt phn t glucose to thnh 2 phn t pyruvate (con ng
carbon). Hai phn t ADP v 2Pi c bin i thnh 2 phn t ATP (con ng cc nhm
phosphate) 4in t (2 ion hydride) c chuyn t 2 phn t glyceraldehydeyt-3- phosphate
n 2NAD
+
(con ng in t).
4.2.5. Bin i pyruvate di iu kin k kh v hiu kh.
Pyruvate l sn phm ca qu trnh ng phn, n ng vai tr quan trng trong s d
ha saccharide. Di iu kin hiu kh, pyruvate b oxy ha thnh acetate, n i vo chu
trnh acid citric v b oxy ha thnh CO
2
v nc. NADH
2
c to thnh bi s loi hydro
ca glyceral dehyde-3-phosphate, c ti oxy ha thnh NAD
+
bi chuyn in t ca n
n O
2
trong qu trnh h hp ca ty th.
Tuy nhin, di cc iu kin ym kh (v d nh c, xng hot ng nhiu, hay cc
thc vt ngp di nc hoc cc vi khun ln men lactic, NADH c to ra bi qu trnh
ng phn khng th l ti oxy ha bi O
2
. S thiu ht ti to NAD
+
c th lm cho t bo
khng c cht nhn in t oxy ha glyceraldehyde-3-phosphate v cc phn ng khc.
Cc t bo sm nht trong s pht trin ca s sng trong khng kh hu nh khng c
oxy v c cc chin lc pht trin xy ra ngoi qu trnh ng phn di cc iu kin hiu
kh. Tt nht l duy tr c kh nng NAD
+
ti to lin tc sut qu trnh k kh bi chuyn
cc in t t NADH
2
n sn phm kh cui cng nh lactate hoc alcohol.
Pyruvate l cht nhn in t cui cng trong s ln men acid lactic.
Khi cc m ng vt khng c cung cp y oxy oxy ha hiu kh pyruvate
v NADH
2
c to thnh trong qu trnh ng phn, NAD
+
s c ti to li t NADH
2
bi s kh ca pyruvate thnh lactate. Trong nhng m khc nhau v cc loi t bo (vng
mc, no, hng cu) cng to ra lactate t glucose di cc iu kin hiu kh; lactate l sn
phm chnh ca s trao i cht trong hng cu. S kh pyruvate c xc tc bi lactac
dehydrogenase to thnh L-izomer ca acid lactic (latate pH7) (hnh 6.20).
Ni chung s cn bng ca phn ng ny thin nhiu v s to thnh lactate bi s thay
i nng lng t do chun m tnh ln.
Trong qu trnh ng phn, s dehydrogen ha ca 2 phn t glyceraldehyde-3-
phosphate t mt phn t glucose to thnh 2 phn t NADH
2
. NADH
2
c dng kh 2
phn t pyruvate thnh 2 phn t lactate v 2 phn t NAD
+
. NADH
2+
khng a cp Proton
vo chui h hp.
Mc d c 2 bc oxy ha kh bin i glucose thnh lactate, khng c s thay i gi
tr trong bc oxy ha ca carbon: trong glucose (C
6
H
12
O
6
) v acid lactic (C
3
H
6
O
3
), t l H:
C l nh nhau. Tuy nhin, mt s nng lng ca phn t glucose c tch ra bi s bin
i ca n thnh lactate, cho s to thnh 2 phn t ATP. Lactate c to thnh bi cc
c hot ng ca cc ng vt c xng sng c th ti to li, n chuyn ra trong mu ri
n gan, y n c bin i thnh glucose. Bn cht ca hin tng ny nh sau: nhng
vn ng vin chy nc rt, oxy khng cung cp cho t bo oxy ha pyruvate to
thnh ATP, m c lc phi s dng glycogen d tr nh l nhin liu to thnh ATP
bi s ng phn, vi lactate nh l sn phm cui cng. Vn ng vin chy nc rt,
lactate trong mu c nng rt cao, n bin i chm chp tr li glucose. Vo thi gian
ngh, oxy li c cung cp cho qu trnh oxy ha hon ton to ATP ti to li
glucose v glycogen gan t lactate hon tr li glycogen mn trc . Chu trnh
bin i glucose thnh lactate v t lactate v li glucose gan c gi l chu trnh Cori
mang tn v chng nh bc hc Carl v Gerty Cori nghin cu qu trnh ny vo nhng
nm 1930 v 1940.
Nhiu vi sinh vt ln men glucose v cc hexose khc to thnh lactate. V d
lactobacilli v streptococci ln men lactose trong sa thnh acid lactic. S phn ly acid lactic
thnh lactate v H
+
trong hn hp ln men pH thp loi casein v cc protein sa khc v
Hnh 6.20. S kh pyruvat thnh lactat
xy ra s kt ta. Di cc iu kin thch hp, n ng cc thnh fomat hoc sa chua, ph
thuc vo vi sinh vt c lin quan
4.2.6. Qu trnh ng phn c th tm tt bng 11 phn ng sau:
1/ Hot ho glucose 2/ ng phn ho
3/ Hot ho Fructose 6-P 4 v 5/ Tc dng ca Aldose v ng phn ho
6/ Dn lin kt
7/ Phosphoryl ho 8/ ng phn ho
9/ Dn lin kt (loi nc) 10/ Phosphoryl ho
11/ Kh to lactat
4.2.7. ngha ca qu trnh ng phn:
ngha v nng lng: qu trnh ng phn din ra trong m bo ng vt trong
iu kin m bo thiu oxy do mu cung cp khng y . Trong qu trnh ny phn t
glucose b phn gii thnh 2 phn t acid lactic v t bo thu c 2ATP tng ng 20kcal.
Khi oxy ho hon ton th mt phn t glucose cho 686 kcal, nh vy hiu sut ca qu trnh
ng phn l rt thp ( 3%). Do acid lactic hay ni chung l cc sn phm ca qu trnh
ln men l cn cha rt nhiu nng lng. Trong thc t khi ng vt hot ng i hi rt
nhiu nng lng m iu kin ym kh li tng ln, cho nn qu trnh ng phn xy ra rt
mnh v mt s lng rt ln phn t glucose b v thnh acid lactic. Do nhng m bo,
bp tht hot ng trong iu kin ym kh lu, acid lactic sinh ra nhiu, b ng gy ri
lon trao i cht cc b , lm thay i pH ca m bo nh hng ti trng thi keo ca
protein, y l nguyn nhn gy nn trng thi mi mt.
ngha v sinh tng hp: Qu trnh ng phn ngoi vic khai thc nng lng, n
cn to ra nguyn liu tng hp lipid l phospho glyceral v acetyl coenzymeA:
Acid pyruvic ----------- > Acetyl coenzymeA, y l nguyn liu tng hp acid bo.
4.2.8. Acid lactic v vng Cori
Acid lactic b ng m bo l nguyn nhn gy ra s mi mt ca c th v khi
ng n gy nh hng ti trng thi keo ca c, cho nn trong c th c mt c ch gii
thot s ng acid lactic. Khi c th ngh ngi, mu c lu thng bnh thng th acid
lactic ng t cc m bo s chuyn ra mu, t mu chuyn v gan, thm vo cc t bo
gan, y c mt h thng enzyme gn ging nh h thng enzyme i ngc li qu trnh
ng phn tng hp t acid lactic thnh glucose v t glucose ny c th li thnh glycogen
ri li thnh glucose a vo mu ch ti cc m bo. l con ng gii thot acid
lactic ng m bo v tit kim c ngun glucid ca c th. Acid lactic khng b o
thi ra ngoi nh cc cht c khc. Qu trnh c biu din bng vng Cori (hnh 6.21.).
C Mu Gan
Glucose <--------------- Glucose < ----------- Glucose

Glucogen

Glucose

Acid lactic ---------- > Acid lactic ----------- > Acid lactic
Hnh 6.21. Vng Cori
bp tht khi iu kin cung cp oxy c ci thin th khong 4/5 lng acid lactic
hnh thnh c a ra mu v gan cn 1/5 c th oxy ho ngay theo con ng phn gii
hiu kh. C th c tp luyn nhiu th chu trnh Cori hot ng tt, thi gian gii thot acid
lactic khi c bp nhanh nn lu mi.
4.3. Qu trnh ln men ru ethylic
Qu trnh ln men ru ethylic do t bo saccharomyces cerevisiae thc hin. Khi
glucose c a vo t bo th h thng enzyme phn gii glucose ca n hot ng v to
ra ATP cho t bo cn sn phm cui cng l ru ethylic c tng ra ngoi mi trng.
Nm men v mt s vi sinh vt khc ln men glucose thnh ru ethylic v CO
2
.
Glucose c bin i thnh pyruvate ging nh qu trnh ng phn v pyruvate c bin
i thnh ru ethylic v CO
2
. Qu trnh gm 2 bc.
Bc th nht, pyruvate b kh carboxyl, c xc tc bi pyruvate decarboxylase.
Pyruvate decarboxylase i hi Mg
2+
v c s lin kt vi coenzyme thiamin pyrophosphate
(TPP).
Bc th 2, acetaldehyde c kh thnh ethanol vi NADH
2
nhn c t
dehydrogenase ha glyceraldehyde3-phosphate qua hot ng ca alcohol dehydrogenase.
Ethanol v CO
2
, thay cho lactate, v vy chng l sn phm cui cng ca s ln men ru
(hnh 6.22). Tng quan s cn bng ca s ln men l:
Glucose + 2 ADP + 2 Pi 2 ethanol + 2 CO
2
+ 2 ATP + 2 H
2
O
Trong s ln men ru ethylic khng c s thay i c gi tr v t l nguyn t hydro
vi carbon khi glucose c ln men (t l H: C = 12/6 =2) thnh 2 ethanol v 2 CO
2
(t l
Hnh 6.22. S to thnh
ru ethylic
H=C kt hp =12/6=2). Nh vy trong qu trnh ln men, t l H: C ca cc cht tham gia
phn ng ha hc v cc sn phm gi nguyn nh nhau.
Pyruvate decarboxylase c trong nm men bia v bnh m v trong tt c cc c th
khc nhau, n lm tng s ln men alcohol, chng cng c trong mt s thc vt. CO
2
c
to thnh bi s decarboxyl ha pyruvate trong nm men bia m bo c tnh bo ho
carbonate ca champagne. S n ca bnh m khi nng l do CO
2
c lin quan n pyruvate
decarboxylase khi trn nm men vi ng. Enzyme ny khng c mt trong cc m ng vt
c xng sng v mt s c th khc nh vi khun ln men lactic.
Alcohol dehydrogenase c trong nhiu c th k c ngi.
4.4. S ln men vi sinh vt to cc sn phm c gi tr thng mi.
Lactate v ethanol l cc sn phm ph bin ca s ln men vi sinh vt, ngoi ra cn c
nhng sn phm ln men khc cng c to ra. Nm 1910 Chaim Waizann (sau ny tr
thnh tng thng u tin ca Israel) pht hin ra vi khun Clostridium acetobutylicum ln
men tinh bt thnh butanol v acetone. Pht hin ny m ra lnh vc ln men cng nghip,
trong cc nguyn liu giu polysaccharide (th d tinh bt ng hoc r ng) c s
dng nui cy cc vi sinh vt c bit cho s ln men chng thnh cc sn phm c gi tr
ln: cc acid formic, acetic, propionic,bytyric v succinic, glycerol, isopropanol, butanol v
butanediol.
4.5. Cc monosaccharide khc c th i vo con ng ng phn.
Trong hu ht cc c th, cc hexose khc cng c th i vo ng phn sau khi c
phosphoryl ha.
D- Fructose dng t do c nhiu trong qu v c to thnh khi thu phn sacarose
trong rut non c th phosphryl ha bi hexokinase. Hexokinase ny hot ng trn nhiu
hexose khc nhau.
Fructose + ATP
+ 2
Mg
fructose -6-phosphate + ADP
Hnh 6.23. S chuyn ho Fructose-1-phosphate
Trong c v thn ca ng vt c xng sng, con ng ny l ch yu. Tuy nhin,
trong gan fructose li i vo qu trnh ng phn bng mt con ng khc. Enzyme
fructokinase ca gan xc tc s phosphoryl ho C1 ch khng phi C6.
Fructose-1-phosphate sau b ct to thnh glyceraldehyde v dihydroxyacetone
phosphate bi fructose-1-phosphate aldolase (hnh 6.23).
Dihydroxyacetone phosphate c bin i thnh glyceraldehyde-3-phosphate bi
enzyme ng phn triose phosphate isomerase. Glyceraldehyde c phosphoryl ha bi
ATP v triose kinase thnh glyceraldehyde-3-phosphate:
Glyceraldehyde +ATP
+ 2
Mg
Glyceraldehyde-3-phosphate +ADP.
V vy c 2 sn phm ca s thu phn fructose i vo con ng ng phn l
glyceraldehyde-3-phosphate.
D-Galactose c phn gii bi s thu phn ca disaccharide lactose (ng sa), u
tin b phosphoryl ha C-1 do ATP di s xc tc ca enzyme galactokinase:
Galactose + ATP Galactose-1-phosphate + ADP
Galactose-1-phosphate sau c bin i thnh epimer ca n C-4 thnh glucose-
1-phosphate bi mt lot phn ng trong c s tham gia ca uridine diphosphate (UDP)
nh l cht mang tng t coenzyme (coenzyme like) ca cc nhm hexose (hnh 6.24).
C mt s bnh di truyn ngi, trong s trao i galactose b nh hng. Trong
phn ln dng chung ca galactosemia, enzyme galactose 1-phosphate uridinetransferase
(hnh 6.24) b khim khuyt di truyn, ngn tr s bin i galactose thnh glucose. Nhng
dng khc nhau ca galactosemia khi galactokinase ca chng hoc UDP glucose 4-
epimerase b khim khuyt di truyn.
D-Mannose tng ln khi phn gii nhiu polysaccharide v glucoprotein c trong thc
phm c th b phosphoryl ha C-6 bi hexokinase:
Mannose + ATP
+ 2
Mg
Mannose -6-phosphate + ADP
Mannose 6-phosphate sau c ng phn ha bi hot ng ca phosphomannose
isomerase to thnh fructose-6-phosphate, cht trung gian ca qu trnh ng phn.
Hnh 6.24. Con
ng bin i D-
galactose thnh D-
glucose. Qu trnh bin
i qua dn xut ng
nucleotide, UDP-galactose
c to thnh khi
galactose-1-phosphate
chuyn cho glucose-1-
phosphate t UDP-
glucose. UDP-galactose
sau c bin i bi
UDP-glucose-4-epimerase
thnh UDP-glucose. UDP-
glucose c m vng qua
1 vng khc ca chnh
phn ng. Tc dng ca
chu trnh ny l s bin
i galactose-1-phosphate,
khng to thnh hoc tiu
th UDP-galactose hoc
UDP-glucose.
5. S oxy ho glucose trong iu kin c oxy
Khi vic np oxy t mu ca m bo c y th s chuyn ho trung gian
glucose s i theo hng khc, nhn chung khi c mt oxy th c 2 cch phn gii glucose:
1. Oxy ho theo chu trnh Krebs.
2. Oxy ho theo chu trnh pentose phosphate.
Kh nng th 2 khng phi c tt c cc m bo, m ch c mt s m bo nh m
lipid, tuyn thng thn, tuyn sinh dc... l nhng ni m qu trnh oxy ho gn cht vi qu
trnh tng hp cc cht nh acid bo, cc hormone. V oxy ho theo chu trnh pentose
Hnh 6.25. Tng qut cc con ng ca cc hexose, cc disaccharide v cc polysaccharide i
vo trung tm con ng ng phn.
phosphate vi mc ch chnh l to ra cc ng lng kh NADPH
2
cho qu trnh sinh tng
hp... Trong iu kin bnh thng th kh nng 1 l ch yu.
5.1. Oxy ho theo chu trnh Krebs. (Chu trnh acid citric, chu trnh cc acid
tricacboxylic)
Phn ln cc t bo nhn chun v cc vi khun hiu kh thc hin khai thc nng
lng bng con ng oxy ha cc nhin liu sinh vt ca chng bng con ng oxy ho
theo chu trnh Krebs to thnh CO
2
v H
2
O. Oxy ho theo chu trnh Krebs th pyruvate
c hnh thnh trong qu trnh phn gii glucose khng b kh thnh lactate, ethanol hoc
mt s sn phm ln men khc nh xy ra trong iu kin k kh, m c thay th bng s
kh thnh CO
2
v H
2
O pha hiu kh ca qu trnh trao i cht, gi l qu trnh h hp.
Qu trnh h hp xy ra vi 3 bc chnh (hnh 6.26). Trong bc u tin, cc phn t
nhin liu (glucose, acid bo v mt s acid amin) c oxy ha thnh acetyl-coenzyme A
(acetyl-CoA). Bc th hai, cc nhm acetyl-CoA ny c i vo chu trnh acid citric, chu
trnh ny oxy ha chng thnh CO
2
. Nng lng c gii phng ra bi qu trnh oxy ha
c tn ti trong NADH
2
v FADH
2
. Bc th 3 ca qu trnh h hp l cc cofactor
NADH
2
v FADH
2
i vo chui h hp, cc proton (H
+
) v in t ca n c vn chuyn
trong cc thnh vin ca chui h hp, nng lng ca chng c nh dn v cui cng kh
O
2
thnh H
2
O. Trong qu trnh ny in t chuyn v bc nng lng thp (bc nng
lng ban u) s nng lng gii phng ra ch yu c tch lu vo ATP. Qu trnh ny
c gi l phosphoryl ha. Qu trnh h hp phc tp hn qu trnh ng phn v l bc
tin ha ca sinh vt.
Bc th 3 ca qu trnh l s h hp m bo tc l qu trnh chuyn in t v
phosphoryl ha oxy ha c trnh by chng V. Trong chng ny chng ta xem xt
qu trnh oxy ha hon ton phn t pyruvate v chu trnh acid citric, cn c gi l chu
trnh acid tricarboxylic hay chu trnh Krebs. Chng ta xem xt cc phn ng trong chu trnh
v cc enzyme xc tc cho chng. Bi v cc phn ng trung gian ca chu trnh acid citric
thng c s dng nh cc tin cht sinh tng hp, mt s phn ng trung gian ny quan
trng chu trnh tip tc hot ng.
5.1.1. S to thnh acetate.
Chu trnh Krebs l con ng oxy ho khng ch vi ng m cn l con ng oxy
ho vi tt c cc hp cht hu c t thc n a vo
cc sinh vt hiu kh, glucose v cc ng khc, cc acid bo v hu ht cc acid
amin b oxy ha hon ton thnh CO
2
v H
2
O bng chu trnh acid citric. Trc khi chng c
th i vo chu trnh th chng phi c chuyn thnh acetylCoA l cht ch yu i vo chu
trnh acid citric. Nhiu carbon ca acid amin cng i vo chu trnh bng cch ny hoc phn
gii thnh cc cht trung gian khc ca chu trnh. Trc ht chng ta xt qu trnh chuyn ho
t pyruvate do qu trnh ng phn to ra thnh acetyl-CoA v CO
2
bi tp hp ca 3
enzyme, gi l phc hp pyruvate dehydrogenase, nh v trong th ht si ca cc t bo
nhn chun v t bo cht ca t bo nhn x.
Phc hp pyruvate dehydrogenase, c nghin cu rt k, l mt phc hp c 5
cofactor tham gia vo phn ng, tt c cc coenzyme u c bt ngun t cc vitamin.
Phc hp pyruvate dehydrogenase l dng gc cho 2 phc hp enzyme quan trng khc l:
Hnh 6.26: Qu
trnh trao i cht ca
protein, lipde v glucide
xy ra trong 3 bc ca
qu trnh h hp t bo.
bc 1: oxy ha cc
acid bo, glucose v mt
s acid amin to acetyl-
CoA. Bc 2 xy ho
acetyl-CoA bng chu
trnh acid citric bao gm
4 bc, trong cc cp
H cao nng v in t
b tch ra. Bc 3: Cc
cp H cao nng v in
t ny c mang bi
NADH
2
v FADH
2
i
vo chui h hp
mng trong ca ty th
(hoc mng sinh cht
vi khun)- trong chui
h hp chng kh O
2
thnh H
2
O. cp proton
v in t ny iu
khin qu trnh tng hp
ATP trong qu trnh
phosphoryl ha oxy ha.
-cetoglutarat dehydeogenase (ca chu trnh acid citric) v chui m -cetoacid
dehydeogenase c pht trin trong s thoi ho ca mt vi acid amin.
Hnh 6.27. Phn ng tng qut c xc tc bi phc hp pyruvate dehydrogenase
Pyruvate b oxy ha thnh acetyl-CoA v CO
2
Hnh 6.28. Cu trc ca coenzyme A. Mt nhm hydroxyl ca acid pantotenic kt hp
vi mt phn na ADP c sa i bi mt lin kt phosphate este v nhm carboxyl ca
n c gn vo -mercapto ethylamine trong lin kt amide. Nhm hydroxyl v tr 3 ca
phn na ADP c nhm phosphate khng c mt trong ADP ca chnh n. Nhm SH ca
na mercapto thylamine nh dng mt thioeste vi acetate trong acetyl-CoA.
Phn ng tng qut c xc tc bi phc hp pyruvate dehydrogenase l decarboxy
ha oxy ha, mt qu trnh oxy ha khng thun nghch trong nhm carboxyl chuyn t
pyruvate nh mt phn t CO
2
v 2 carbon cn li to nhm acetyl-CoA (hnh 6.27).
NADH
2
c hnh thnh trong phn ng ny mang cp proton v in t ca n vo
chui h hp (hnh 6.26) ti O
2
hoc trong cc vi sinh vt k kh, ti mt cht nhn in t
tip theo chng hn nh lu hunh. in t ny chuyn ti oxy cui cng to ra 3 phn t
ATP trn mt cp in t. Tnh khng thun nghch ca phn ng pyruvate dehydrogenase
c chng minh bi cc th nghim nh du ng v: CO
2
c nh du phng x
khng th gn li vi acetyl CoA.
Phc hp pyruvate dehydrogenase cn 5 coenzyme.
S kh hydro v decarboxyl ha pyruvate acetyl-CoA (hnh 6.27) cn ti s tham gia
ca cc enzyme vi 5 coenzyme khc nhau hoc cc nhm ph l thiamin pyrophosphate
(TPP), flavin adenine dinucleotide (FAD), coenzymeA (CoA), nicotinamide adenine
dinucleotide (NAD) v lipoate. Bn vitamin l cc thnh phn trng yu ca h thng ny l:
thiamin (B
1
) trong TPP, riboflavin (B
2
) trong FAD, niaxin trong NAD v pantotenate trong
coenzyme A.
Nhm thiol phn ng:
Coenzyme A c mt nhm thiol (-SH) hot ng (hnh 6.28), vai tr ca n nh mt
cht mang acyl trong cc phn ng trao i cht. Cc nhm acyl c lin kt vi nhm thiol
to thnh thioeste. V nng lng t do ca qu trnh thu phn tng i cao nn cc thioeste
c mt nhm acyl c kh nng chuyn cho cc nhm acyl ca chng ti cc phn t cht nhn
khc nhau. Nhm acyl c gn vo Coenzyme A v vy hot ha nhm chuyn.
Hnh 6.29. Acid lipoic trong lin kt amide vi chui bn ca mt phn Lys l nhm
prosthetic ca dihydrolipoyl transacetylase (E
2
). Nhm lipoyl dng oxy ha (disulfide) hoc
dng kh (didhiol) v c th hot ng nh mt cht mang c nhm hydro v nhm acetyl
(hoc acyl khc)
Cofactor th 5 cho phn ng pyruvate dehydrogenase l lipoate (hnh 6.29), c 2 nhm
thiol, c hai u ng vai tr nh cofactor. dng lipoate kh th c 2 nguyn t lu hunh
u c mt trong cc nhm SH nhng cc sn phm oxy ha mt lin kt disunfide (-S-S)
ging nh gia 2 nhm Cys trong mt protein. V kh nng tham gia cc phn ng oxy ha
kh nn lipoate c th p ng c hai nh mt cht mang in t v cht mang acyl, c hai
chc nng ny u quan trng trong hot ng ca phc hp pyruvate dehydrogenase.
Phc hp pyruvate dehydrogenase gm c 3 enzyme khc nhau:
Phc hp Pyruvate Dehydrogenase gm c v s cc bn sao ca mt trong 3 enzyme
Pyruvate Dehydrogenase (E
1
); dihydrolipoyl transacetylase (E
2
) v dihydrolipoyl
dehydrogenase (E
3
) (bng 6-1). S lng cc bn sao ca mi di n v l khc nhau do
kch c ca phc hp cc sinh vt l khc nhau. Phc hp Pyruvate Dehydrogenase c
tch ra t E.coli (Mp > 4,5. 10
6
), ng knh khong 45nm, thng ln hn mt ribosome v
c th hnh dung di knh hin vi in t (hnh 6.30). Li ca tp hp l ni m cc
enzyme khc tn cng. Trong phc hp t E.coli gm 24 bn sao ca chui polypeptide, mi
bn sao cha 3 phn t lin kt ha tr lipoate, cu thnh nn li. i vi phc hp t ng
vt c v, c 60 bn sao E
2
v 6 bn sao ca protein c lin quan, protein X cng cha lipoate
lin kt ng ha tr. S tn cng ca lipoate vo u tn cng ca cc chui bn Lys trong
E
2
to ra cc nhm acetyl t mt v tr hot ng ti mt v tr khc trong phc h Pyruvate
Dehydrogenase. Lin kt vi li ca cc phn t E
2
l 12 bn sao ca Pyruvate
Dehydrogenase (E
1
), mi bn sao c to phc t 2 di n v ging nhau, v 6 bn sao
ca dihydro lipoyl dehydrogenase (E
3
), mi bn sao cng c to phc t 2 di n v
ging nhau. Pyruvate dehydrogenase (E
1
) cha lin kt TPP, v dihydrolipoyl dehydrogenase
(E
3
) cha lin kt FAD. Hai protein iu ho cng l thnh phn ca phc hp Pyruvate
dehydrogenase (protein kinase v protein phosphotase) s c tho lun sau.
Bng 6.1: Thnh phn di n v ca phc hp Pyruvate dehydrogenase E.coli.
Enzyme Coenzyme Khi lng phn t
ca di n v
S lng di n
v trn 1 phc hp
Pyruvate dehydrogenase (E
1
) TPP 96,000 24
Dihydrolipoyl transacetylase
(E
2
)
Lipoate,
CoA
65,000 70,000 24
Dihydrolipoyltransacetyrase (E
3
) FAD,NAD 56,000 12
Cc cht trung gian lin kt vi b mt enzyme.
Hnh 6.30. Cc bc trong qu trnh decarboxyl ha
oxy ha pyruvate thnh acetyl CoA nh phc h
enzyme dehydrogenase. bc C pyruvate phn ng
vi thiamin pyrophosphate (TPP) ca pyruvate
dehydrogenase (E
1
). Pyruvate dehydrogenase cng
thc hin bc C chuyn 2 in t v nhm acetyl t
TPP thnh dng oxy ha ca nhm lipoyl lysyl ca
enzyme li, cn transacetylase (E
2
) thnh dng acetyl
thiosete ca nhm lipoyl kh. Bc C nhm -SH ca
CoA v dng kh (didhiol) ca nhm lipoyl. bc C
dihydrolipoyl dehydrogenase (E
3
) thc y s vn
chuyn 2 nguyn t hydro t cc nhm lipoyl kh ca
E
2
ti nhm prosthetic FDA ca E
3
, hnh thnh nhm
lipoyllysyl oxy ha ca E
2
(vng). bcC, nhm
FADH
2
kh trn E
3
chuyn mt ion hydride ti NAD
+
hnh thnh NADH. Lc ny phc hp enzyme sn sng
cho chu trnh xc tc khc.
Hnh 6.30. cho thy s phc hp dehydrogenase thc hin 5 phn ng decarboxyl
ha v dehydrogenase ha pyruvate. Bc C phn ng c xc tc bi pyruvate
decarboxylase, C-1 ca pyruvate c gii phng di dng CO
2
, v C-2 trong pyruvate oxy
ha mt aldehyde tn cng TPP nh mt nhm hydroxyethyl. Bc C nhm ny oxy ha
thnh mt acid carboxylic (acetate). Hai in t c chuyn vo phn ng oxy ha lm bin
i S-S- ca mt nhm lipoyl trn E
2
thnh 2 nhm thiol (-SH). Acetate c to thnh
trong phn ng oxy ho kh ny u tin b este ha thnh mt trong cc lipoyl SH, sau
c chuyn ti CoA hnh thnh acetyl CoA (bcC). V vy nng lng ca qu trnh
oxy ha iu khin thng tin ca mt thioester cao nng ca acetate.
Phn cn li ca cc phn ng c xc tc bi phc hp pyruvate dehydrogenase (cc
bc C v C chuyn in t cn thit ti to li dng disulfide ca nhm lipoyl ca E
2

chun b phc hp enzyme cho chu trnh oxy ha khc. Cc in t chuyn t nhm hydroxy
ethyl c bt ngun t pyruvate cui cng tn ti dng NADH
2
sau khi i qua FAD.
Trung tm ca quy trnh l lp cc nhnh lipoyllysyl ca E
2
thng qua 2 in t v
nhm acetyl bt ngun t pyruvate t E
1
n E
3
.
Cc ng vt thiu thiamin khng th oxy ha pyruvate mt cch bnh thng, thiamin
c bit quan trng trong no.
5.1.2. Cc phn ng ca chu trnh acid citric.
Nh ta bit acetyl -CoA c hnh thnh t pyruvate nh th no, by gi chng ta
hy xem xt chu trnh acid citric. u tin chng ta lu l c s khc nhau c bn gia qu
trnh ng phn v chu trnh acid citric. Qu trnh ng phn gm mt lot cc phn ng
c xc tc bi enzyme. Trong khi chu trnh acid citric th khp kn (hnh 6.31), acetyl
CoA cho nhm acetyl ca n vi oxaloacetate to citrate 6 carbon, phn t ny c
hydro ha v mt CO
2
to thnh hp cht 5 carbon -cetoglutarate. Tip theo mt tip
CO
2
v to thnh hp cht 4 carbon succinate v 1 phn t CO
2
th hai. Sau succinate
c bin i trong 3 phn ng thnh oxaloacetate 4 carbon v chu trnh li bt u.
Oxaloacetate li sn sng phn ng vi phn t acetyl CoA khc bt u chu trnh th 2.
Trong mi chu trnh ca chu trnh, mt nhm acetyl (2 carbon) gn vo v 2 phn t CO
2
tch
ra, ng thi mt phn t oxaloacetate c s dng to citrate nhng sau mt lot cc
phn ng oxaloacetate c ti sinh. Do mt phn t oxaloacetate v l thuyt th c th
oxy ha mt lng ln cc nhm acetyl ring bit. Bn trong 8 phn ng trong chu
trnh ny l phn ng oxy ha, trong nng lng ca qu trnh oxy ha c duy tr vi
hiu qu cao to ra cc cofactor kh (NADH
2
v FADH
2
).
V vy chu trnh acid citric l trung tm trao i nng lng. Cc cht trung gian 4 v 5
carbon ca chu trnh cung cp cc tin cht sinh tng hp. thay th cho mc ch ny th
cc cht trung gian b thay i, cc t bo thc hin cc phn ng b nh c m t.
Eugene Kennedy v Albert Lehninger (1948) ch ra rng cc t bo nhn chun,
ton b cc phn ng ca chu trnh acid citric u xy ra ty th. Ty th cha tt c cc
enzyme v coenzyme cn thit cho chu trnh acid citric. Ty th cng cha cc enzyme xc tc
phn ng oxy ha cc acid bo to acetyl-CoA v cc acid amin, chng hn mt s acid amin
c tng hp t -cetoglutarate, succinyl CoA hoc oxaloacetate. V vy cc t bo nhn
chun khng quang hp, ty th l ni ch yu xy ra cc phn ng oxy ha to nng lng v
tng hp ATP. Cn cc t bo nhn chun quang hp th ty th l ni chnh to ATP vo
ban m, nhng ban ngy th lc lp to phn ln ch phm ny. Phn ln cc t bo nhn x
cha cc enzyme ca chu trnh acid citric trong phn t bo cht ca chng v mng sinh cht
thc hin chc nng tng ng vi mng ty th trong qu trnh tng hp ATP.
Cht dn dt acetyl CoA l oxaloacetate. Ngun cung cp oxaloacetate c 2 ngun:
T acid aspartic theo con ng kh amin:
T acid pyruvic c carboxyl ho (y l con ng chnh):
Chu trnh acid citric c 8 phn ng:
Chu trnh acid citric c thc hin bi mt h thng enzyme hot ng lin hon vi
nhau (multyenzyme) theo mt vng nn cn gi l vng acid citric hay l vng Krebs (hnh
6.31). Trong 8 phn ng ca chu trnh acid citric, s nhn mnh c bit s bin i ha hc
to citrate t acetyl-CoA v oxaloacetate b oxy ha thnh CO
2
v nng lng ca qu trnh
oxy ha ny tn ti dng cc coenzyme kh NADH
2
v FADH
2
.
C CC C S hnh thnh citrate: phn ng u tin ca chu trnh l s kt hp ca acetyl-CoA
v oxaloacetate to ra citrate, phn ng c xc tc bi citrate hydratse.
Trong phn ng ny, carbon methyl ca nhm acetyl kt hp vi nhm carbonyl (C-2)
ca oxaloacetate. Cidroyl-CoA l mt cht trung gian chuyn tip. N tn ti trn v tr hot
ng ca enzyme v b thu phn to thnh CoA t do v citrate sau c gii phng khi
v tr hot ng. Qu trnh thu phn ca cht trung gian thioester cao nng to phn ng
thun gii phng nng lng. CoA tn ti trong phn ng ny c lp li chu trnh, n sn
sng tham gia kh carboxyl ha bng cch oxy ha phn t pyruvate khc nh phc hp
pyruvate dehydrogenase to thnh phn t acetyl-CoA khc i vo chu trnh.
Hnh 6.31. Cc phn ng ca chu trnh acid citric. Cc nguyn t carbon c bt
ngun t acetate ca acetyl-CoA. Cc bc C, C v C khng thun nghch trong t bo,
cn tt c cc phn ng khc l phn ng thun nghch.
C CC C S hnh thnh isocitrate thng qua cis- Aconitate: enzyme aconitase (thng gi l
aconitate hydratase) xc tc qu trnh bin i nghch citrate thnh isocitrate thng qua dn
xut trung gian acid tricarboxylic l cis-aconitate thng khng tch ra t v tr hot ng.
Aconitase c th kch thch s b sung H
2
O thun nghch to lin kt i cis-aconitate
lin kt enzyme theo 2 cch khc nhau, mt to citrate v mt cch khc to isocitrate. V vy
hn hp cn bng pH7,4 v 25
0
C cha t hn 10% isocitrate. Aconitase cha mt trung tm
st-lu hunh hot ng c trong lin kt c cht ti v tr hot ng v trong qu trnh xc tc
b sung v loi nc (hnh 6.32).
Hnh 6.32. Trung tm st - lu hunh vi
aconitase hot ng lin kt c cht v xc tc. 3
gc Cys ca enzyme lin kt vi 3 nguyn t st
trung tm st lu hunh (mu vng); nguyn t
st th 4 lin kt vi mt trong cc nhm carboxyl
ca citrate (mu xanh).
C CC C Qu trnh oxy ha isocitrate thnh -
cetoglutarate v CO
2
. Trong bc tip theo,
isocitrate dehydrogenase xc tc qu trnh
decarboxyl ha oxy ha isocitrate to thnh -
cetoglutarate.
C 2 dng isocitrate dehydrogenase khc nhau, mt dng cn NAD
+
nh cht nhn in
t v dng kia cn NADP
+
. Cc phn ng khp kn c xc tc bi 2 isozyme khc. Enzyme
c NAD
+
c tm thy trong ty th v p ng chu trnh acid citric to ra -cetoglutarate.
Cn isozyme da vo NADP
+
th c tm thy c trong ty th v sinh cht.
C CC C Qu trnh oxy ha -cetoglutarate thnh succinyl CoA v CO
2
: Bc tip theo l
qu trnh decarboxyl ho oxy ha, trong bc ny -cetoglutarate bin i thnh succinyl
CoA v CO
2
bi hot ng ca phc hp cetoglutarate dehydrogenase; NAD
+
tham gia nh
cht nhn in t.
Phc hp -cetoglutarate dehydrogenase cu to t 3 enzyme ging nh E
1
, E
2
, E
3
ca
phc hp pyruvate dehydrogenase nhng chng c trnh t sp xp acid amin khc nhau.
C CC C Qu trnh bin i succinyl CoA thnh succinate:
Succinyl CoA cng nh acetyl-CoA, c nng lng t do thu phn lin kt thioester
cao (
'
G = -36KJ/mol). Trong bc tip theo ca chu trnh, ph v lin kt ny iu khin
qu trnh tng hp mt lin kt phosphoanhydride GTP hoc ATP v succinate cng c
hnh thnh trong qu trnh.
Enzyme xc tc cho phn ng l succinyl CoA synthetase hoc succinyl kinase.
Phn ng to nng lng c mt bc trung gian m trong phn t enzyme b
phosphoryl ha gc His v tr hot ng (hnh 6.33). Nhm phosphate ny c mt nhm
c kh nng bin i ln, n bin i ATP (hoc GTP) thnh ADP (hoc GDP).
S bin i ATP (hoc GTP) tiu tn nng lng ly t qu trnh decarboxyl ha oxy
ha cetoglutarate. l mt v d v qu trnh phosphoryl ha c cht ging nh qu trnh
tng hp ATP oxy ho glyceraldehyde 3 phosphate trong qu trnh ng phn. Khc vi
phn ng phosphoryl ha c cht, qu trnh phosphoryl ha trong ty th hoc lc lp c
thc hin nh h thng enzyme lin kt mng nh c ch to nng lng qua s phn b
chnh lch proton bn mng.
Hnh 6.33: Cc cht trung gian trong phn ng succinyl-CoA synthetase. bc C CC C mt
nhm phosphate thay th CoA trong succinyl CoA lin kt enzyme to mt acyl phosphate cao
nng. bc C CC C succinyl phosphate cho nhm His trn enzyme nhm phosphate ca n, to
enzyme phosphohistidine cao nng. bc C CC C nhm phosphate c chuyn t nhm His ti
phosphate cui cng ca GDP, to GTP.
GTP c hnh thnh nh succinyl CoAsynthetase c th cho nhm phosphate cui
cng ca n cho ADP to ATP nh phn ng thun ca nucleotide diphosphate kinase:
GTP +ADP GDP +ATP G
0
= 0 KJ/mol
Oxy ha succinate thnh fumarate:
Succinate c hnh thnh t succinyl CoA b oxy ho thnh fumarate nh succinate
dehydrogenase cha flavoprotein. t bo nhn chun, succinate dehydrogenase nm trn
mng ty th (cn t bo nhn x th enzyme ny nm trn mng t bo cht); n ch l
enzyme ca chu trnh acid citric m gn vi mng. Cc in t c chuyn t succinate qua
FAD v trung tm st lu hunh trc khi i vo chui h hp v c s dng tng hp
2 phn t ATP trn mi cp in t.
C CC C Hydrat ha fumarate to malate: Qu trnh hydrate ha nghch fumarate thnh L-
malate c xc tc bi fumarase (fumarate hydratase) enzyme ny c hiu cao: n xc tc
qu trnh thu phn lin kt i ca fumarate nhng khng hot ng trn malate, ng phn
Cis ca fumarate.
Oxy ha malate thnh oxaloacetate: phn ng cui cng ca chu trnh acid citric,
L malate dehydrogenase ph thuc NAD xc tc qu trnh oxy ha L-malate thnh
oxaloacetate.
Cn bng phn ng lch nhiu v pha malate nhng trong thc t th oxaloacetate va
c to thnh tham gia ngay vo chu trnh nn nng thc ca n lun thp, do chiu
phn ng lun hng v pha to oxaloacetate.
Nng lng ca cc qu trnh oxy ha trong chu trnh
By gi chng ta c mt chu trnh hon thin chu trnh acid citric (hnh 6.34).
Mt nhm acetyl cha 2 nguyn t carbon tham gia vo chu trnh bng cch kt hp vi
oxaloacetate. Hai nguyn t carbon c gii phng khi chu trnh di dng CO
2
vi qu
trnh oxy ha isocitrate v - cetoglutarate, v kt thc chu trnh th mt phn t oxaloacetate
c to ra.
Hnh 6.34. Cc v tr to ra NADH
2
, FADH
2
v GTP ca chu trnh acid citric
Mi chu trnh acid citric to ra 3 NADH
2
, 1 FADH
2
v 1 GTP (hoc ATP). 2 CO
2
c
gii phng ra trong cc phn ng kh carboxyl ha bng oxy ha.
Chng ta bit nng lng c to thnh t qu trnh ng phn (mt phn t
glucose phn gii thnh 2 pyruvate) l 2 phn t ATP. Khi c 2 phn t pyruvate oxy ha
hon ton s to thnh 6 phn t CO
2
trong cc phn ng c xc tc bi phc hp pyruvate
dehydrogenase v cc enzyme ca chu trnh acid citric v cc in t c chuyn ti O
2
qua
chui h hp to ra 38 ATP trn mt phn t glucose. Nhng nng lng t do ca phn t
glucose l 2,840 kJ/mol, khi oxy ha hon ton mt glucose to ra nng lng d tr 38 x
30,5 KJ/mol = 1,160KJ/mol nh vy hiu sut l 40% (bng 6.2).
Bng 6.2. S to thnh ATP trong cc qu trnh h hp mt phn t glucose qua
ng phn, phn ng pyruvate dehydrogenase v chu trnh acid citric.
Phn ng S lng ATP hoc
coenzyme to thnh
S lng ATP
to thnh
Glucose glucose6-phosphate -ATP -1
Fructose6-fructose-1,6-bi -1ATP -1
2 glyceraldehyde 3-
2 1,3- diphosphoglyxerat
2NADH 6
2 1,3-diphosphoglycerate
2 3-phosphoglycerate
2ATP 2
2 phosphoenolpyruvate 2pyruvate 2ATP 2
2 pyruvate 2 acetyl CoA 2NADH 6
2 isocitrate 2 -cetoglutarate 2NADH 6
2 -cetoglutarate 2 succiyl-CoA 2NADH 6
2 succinyl-CoA 2 succinate 2ATP (hoc 2
GTP)
2
2 succinate 2 fumarate 2FADH
2
4
2 malate 2 oxaloacetate 2NADH 6
Tng s
38

5.1.3. Chu trnh acid citric c pht hin nh th no?
Chu trnh acid citric c Hans Krebs a ra ln u tin nh qu trnh oxy ha
pyruvate cc m ng vt nm 1937. tng ny xut hin khi ng nghin cu nh hng
ca cc anion ca acid hu c khc nhau ln t l tiu th oxy ha pyruvate trong m c ngc
b cu. C ny dng bay nn c t l h hp rt cao. Trc cc nh nghin cu, c bit
l Albert Szent Gyorgyi tm thy cc acid dicarboxylic cha 4 carbon c mt trong m
ng vt - succinate, fumarate, malate v oxaloacetate kch thch qu trnh tiu th oxy nh
c. Krebs tha nhn chng v pht hin rng chng cng kch thch qu trnh oxy ha
pyruvate. Hn na, ng cng thy rng qu trnh oxy ha pyruvate nh c cng c kch
thch bi cc acid tricarboxylic 6 carbon: citrate, cis-aconitate v isocitrate v -
cetoglutarate 5 carbon.
Pht hin quan trng th 2 l Krebs cho rng s c mt ca malonate, cht c ch cnh
tranh ca succinate i vi succinate dehydrogenase gy ra s tch ly citrate, -
cetoglutarate v succinate trong dch m c. iu ny chng t rng citrate v -
cetoglutarate l cc tin cht ca succinate.
T nhng d liu ny, Krebs kt lun rng cc acid tricarboxylic v dicarboxylic c
th c sp xp trong mt trnh t logic ha hc bi v s to pyruvate v oxaloacetate vi
m c trong qu trnh tch ly citrate trong mi trng, Krebs suy lun rng trnh t cc
chc nng ny trong mt chu trnh ng hn kiu dy di, s bt u v kt thc ca n lin
kt vi nhau.
Pyruvate + oxaloacetate citrate +CO
2
T cc th nghim n gin ny v suy lun khoa hc, Krebs gi nh ci m ng ta
gi l chu trnh acid citric l con ng chnh cho qu trnh oxy ha carboxylic. T khi pht
hin ra n, chu trnh acid citric khng ch c chc nng trong c m cn trong tt c m thc
vt v ng vt v trong nhiu vi sinh vt hiu kh.
Chu trnh acid citric c t tn ln u tin t cc th nghim c thc hin trn dch
m c.
5.1.4. Chu trnh acid citric cha hon thin ca sinh vt k kh
Tm bc trong chu trnh, qu trnh cho oxy ha cc nhm acetyl 2 carbon n gin
thnh CO
2
c th thy l rt khoa hc ca cc t bo sng. Vai tr ca chu trnh acid citric l
khng ch oxy ha acetate, m con ng
ny cn l trung tm ca trao i cht trung
gian. Cc sn phm cui cng 4 hoc 5
carbon ca nhiu qu trnh trao i cht cng
tham gia vo chu trnh vi t cch nh
nhng nhin liu. V d: oxaloacetate v -
cetoglutarate c to ra t aspartate v
glutamate tng ng khi cc acid amin ny
b phn gii hoc to thnh t cc sn phm
trn khi protein trong ch n ung b
gim.
Phng thc c s dng cc sinh
vt hin i l sn phm tin ha. Trong thc
t, c cc sinh vt k kh s dng mt chu
trnh acid citric cha hon thin khng phi
nh mt ngun nng lng m l tin cht
sinh tng hp (hnh 6.35).
Hnh 6.35. Cc phn ng khng chu k
cung cp cc tin cht sinh tng hp vi khun
sinh trng k kh. Cc t bo ny thiu -
cetoglutarate dehydrogenase v do khng th thc hin chu trnh acid citric hon chnh, -
cetoglutarate v succinyl-CoA tn ti nh cc tin cht trong cc phn ng sinh tng hp khc nhau
(xem hnh 6.36).
Cc sinh vt ny s dng 3 phn ng u tin ca chu trnh acid citric to -
cetoglutarate, nhng chng thiu - cetoglutarate dehydrogenase nn khng th thc hin
hon thin cc phn ng cu chu trnh acid citric. Chng c 4 enzyme xc tc cho s bin i
nghch oxaloacetate thnh succinyl-CoA (hnh 6.35) v cc vi sinh vt k kh to malate,
fumarate, succinate v succinyl CoA t oxaloacetate dng nghch o ca qu trnh oxy
ha bnh thng thng qua chu trnh.
Vi qu trnh tin ha ca vi khun lam to O
2
t nc, bu kh quyn ca tri t tr
nn hiu kh v vi sc p chn lc, cc sinh vt pht trin trao i cht hiu kh, c hiu qu
hn ln men k kh.
5.1.5. Cc cht trung gian ca chu trnh acid citric l cc tin cht sinh tng hp
quan trng.
Hnh 6.36. Cc cht trung gian ca chu trnh acid citric nh cc tin cht trong nhiu con
ng sinh tng hp.
i vi cc sinh vt hiu kh th chu trnh acid citric l mt con ng chuyn ha
lng tnh (n tham gia trong c 2 qu trnh d ha v ng ha). N khng ch ng ha oxy
ha carbon hydrate, acid bo v cc acid amin m n cn cung cp cc tin cht cho nhiu
con ng sinh tng hp (hnh 6.36). Nh hot tnh ca mt vi enzyme ph quan trng m
cc cht trung gian no ca chu trnh acid citric, c bit l -cetoglutarate v
oxaloacetate c th chuyn t chu trnh thnh cc tin cht ca acid amin. Aspartate v
glutamate c cc b khung carbon ging nhau nh oxaloacetate v -cetoglutarate v c
tng hp t chng nh qu trnh chuyn amin ho c bn thng qua aspartate v glutamate,
carbon ca oxaloacetate v -cetoglutarate c s dng xy dng cc acid amin khc
cng nh cc nucleotide purin v pyrimidin. Succinyl-CoA l mt cht trung gian trung tm
trong qu trnh tng hp chu trnh porphyrin ca cc nhm hem, tn ti nh cc cht mang
O
2
(trong hemoglobin v myoglobin) v cht mang in t (trong ty th).
5.1.6. Cc phn ng phc hi li cc cht trung gian ca chu trnh acid citric
Khi cc cht trung gian ca chu trnh acid citric bin i tn ti nh cc tin cht sinh
tng hp th kt qu l gim nng cc cht trung gian s lm chm li s thay i thng
qua chu trnh acid citric. Tuy nhin, cc cht trung gian c th c b sung nh cc phn
ng phc hi (hnh 6.35, 6.36, bng 5.3).
m ng vt, mt phn ng phc hi quan trng l qu trnh carboxy ha ngc ca
pyruvate nh CO
2
to thnh oxaloacetate, c xc tc bi pyruvate carboxylase (bng 5.3).
Ba phn ng phc hi khc cng c ch ra bng 5.3, cc m v cc sinh vt khc nhau,
bin i pyruvate hoc phosphoenol pyruvate thnh oxaloacetate. Khi chu trnh acid citric
thiu oxaloacetate hoc bt c 1 cht trung gian no khc th pyruvate b carboxyl ha thnh
nhiu oxaloacetate hn.
Phn ng pyruvate carboxylase l phn ng phc hi quan trng nht trong gan v thn
ca ng vt c v.
Bng 5.3: Cc phn ng phc hi.
Phn ng M / sinh vt
Pyruvate carboxylase
Pyruvate +
3
HCO +ATP oxaloacetate +ADP + Pi
Gan, thn
PEPcarboxylase
Phosphoenolpyruvate +CO
2
+GTP oxaloacetate + GDP
Tim, c vn
PEPcarboxylase
Phosphoenolpyruvate +
3
HCO oxaloacetate +Pi
Thc vt bc cao,
nm men, vi khun
Enzyme malic
Pyruvate +
3
HCO +NAD (P)H
2
malate +NAD(P)
+
Phn b rng cc
sinh vt nhn chun
v sinh vt nhn x.


Hnh 6.37a: Biotin

Hnh 6.37 b: vai tr ca biotin trong phn ng c xc tc bi pyruvate carboxylase.
Bicarbonate u tin b bin i thnh CO
2
trong 1 phn ng ph thuc ATP. S bin i HCO
3

thnh CO
2
. CO
2
v vy c hnh thnh v tr hot ng sau c b sung vi biotin (bc1).
bc 2, nhm carboxyl chuyn t pyruvate thnh dng oxaloacetate (hnh 6.37). Cc phn ng
carboxyl ha ph thuc biotin khc xy ra nh cc qu trnh trao i cht.
5.1.7. iu ha chu trnh acid citric:
Cc nguyn t carbon t pyruvate vo v i qua chu trnh acid citric c iu ha cht
ch 2 giai on: Bin i pyruvate thnh acetyl CoA (phn ng phc h pyruvate
dehydrogenase) v acetyl-CoA i vo chu trnh (phn ng citrate syntethase). Bi v pyruvate
khng phi l tin cht duy nht to acetyl-CoA (phn ln cc t bo c th nhn acetyl-
CoA nh qu trnh oxy ha cc acid bo v cc acid amin). Cc cht trung gian t cc con
ng khc ny cng quan trng iu ha qu trnh oxy ha pyruvate v chu trnh acid
citric. Chu trnh cng c iu ha nh cc phn ng isocitrate dehydrogenase v -
cetoglutarate hydrogenase (hnh 6.38).
Hnh 6.38. Qu trnh iu ha dng trao i cht t pyruvate thng qua chu trnh acid citric.
Phc hp pyruvate dehydrogenase b c ch cc [ATP]/[ADP]; [NADH]/[NAD
+
], v [acetyl-
CoA]/[CoA] cao. Khi cc t l ny gim th s lm tng hot ha tng ng qu trnh oxy ha
pyruvate c kt qu. T l ca dng thng qua chu trnh acid citric c th b hn ch bi gi tr cc
c cht oxaloacetate v acetyl-CoA hoc bi s gim bc oxy ha m NAD
+
l cofactor. Trong m
c, qu trnh trao i cht to nng lng b p ATP b tiu th.
5.1.8. ngha sinh hc ca chu trnh Krebs
ngha v trao i cht: Chu trnh Krebs l mt c ch oxy ho - kh quan trng
nht, thng qua qu trnh ny phn ln cc cht hu c t thc n c khai thc nng lng
mt cch trit nh glucid, lipid, acid amin u c th trc tip hay gin tip i vo chu
trnh Krebs thng qua cc sn phm ph bin l acetyl CoA, -cetoglutarate, oxalo axetate...
Chnh v th ngoi gi tr l c ch oxy ho kh chu trnh Krebs cn ng vai tr l ng ba
trung gian ca trao i cht, l giao im ca trao i ng, trao i lipid, trao i protein.
Nhng sn phm ca qu trnh trao i ng c th tr thnh sn phm ca trao i protein,
trao i lipid v ngc li. V d -cetoglutarate c th chuyn thnh acid amin. Succinyl
CoA c th huy ng ra trong qu trnh chuyn ho th ceton, qu trnh tng hp Hb...
ngha v nng lng: Thng qua chu trnh Krebs c th sinh vt bo m c
phn ln nhu cu v nng lng. Xt v mt tin ho, cch khai thc nng lng qua chu trnh
Krebs tin b v c hiu xut cao hn nhiu so vi qu trnh phn gii ym kh. Mt phn t
glucose khi oxy ho theo chu trnh Krebs cho ra 38-39 ATP (xem bng 6.2).
(2-3 +6)ATP 6 ATP 24 ATP
(Glucose ------------ > Pyruvat ------------ > AcetylCoA ----------- > Chu trnh Krebs)
Nng lng t do ca phn t glucose l 2,840 KJ/mol, khi oxy ha hon ton mt
glucose to ra nng lng d tr 38 ATP x 30,5 KJ/mol = 1,160KJ/mol nh vy hiu sut l
40%.
Phn nng lng cn li 60% l nhit to ra si m c th. Tuy nhin tu tng lc,
tng m bo i hi nng lng khc nhau m c cch khai thc nng lng khc nhau.
5.2. Cc con ng th cp ca s oxy ha glucose.
cc m ng vt phn ln s tiu th glucose l c d ha trong chu trnh ng
phn thnh pyruvate. Hu ht pyruvate c oxy ha trong chu trnh acid citric. Chc phn
ch yu ca s trao i glucose bi con ng ny l to thnh ATP. Tuy nhin cn c
nhng con ng trao i khc cho nhng sn phm c bit cn thit cho t bo v cc con
ng ny l mt phn trao i th cp ca glucose. Hai con ng nh vy to ra pentose
phosphate v cc acid uronic v ascorbic.
5.2.1. Oxy ho theo chu trnh pentose phosphate (Decarboxy ha oxy ha to thnh
pentose phosphate v NADPH).
Con ng pentose phosphate, cn c gi l con ng phosphogluconate.
Trong nhiu ng vt iu ng ch c bit l trong cc m xy ra s sinh tng hp
cc acid bo v cc Steroid t cc tin cht nh hn trong tuyn v, m m ng vt, v
tuyn thng thn v gan. S sinh tng hp cc acid bo i hi ng lng kh NADPH
2
i vi cc lin kt i v cc nhm carboxyl ca cc hp cht trung gian trong qu trnh ny.
Chc phn th cp ca con ng pentose phosphate l to thnh cc pentose cn thit,
c bit l D-ribose, n c s dng trong sinh tng hp acid nucleic (hnh 6.39).
Hnh 6.39. Chu trnh
pentose phosphate to
NADPH v ribose-5-
phosphate.
Phn ng u tin ca con ng pentose phosphate l s loi hydro ca glucose-6-
phosphate bi glucose-6-phosphate dehydrogenase thnh 6-phosphoglucono lactone, este ni
phn t, n c thu phn thnh acid t do 6-phosphogluconate bi lactonase c bit.
NADP
+
l cht nhn in t to thnh NADPH
2
. Bc tip theo 6-phosphogluconate
dehydrogenase ha v decarboxy ha 6-phospho gluconate thnh dng ketopentose D-
ribulose-5- phosphate, phn ng to thnh phn t NADPH
2
th hai. Sau phosphopentose
isomerase bin i ribulose 5- phosphate thnh ng phn aldose ca n l D-ribose-5-
phosphate (hnh 6.39). Trong mt s m, con ng pentose phosphate kt thc im ny
v phn ng cn bng nh sau:
Glucose-6- phosphate +2NADP +H
2
O ribose-5-phosphate +CO
2
+2NADPH +2H
+
Kt qu l to thnh NADPH
2
kh cc phn ng sinh tng hp v to thnh ribose-
5- phosphate nh l tin cht cho tng hp v to thnh nucleotide.
Trong cc m ch yu i hi NADPH
2
nhiu hn ribose-5- phosphate, cc pentose -
phosphate c to thnh t glucose-6- phosphate trong hng lot phn ng (hnh 6.40).
Hnh 6. 40. Cc phn ng khng oxy ha ca con ng pentose phosphate bin i
pentose phosphate tr li thnh cc hexose phosphate, cho php cc phn ng oxy ha
(xem hnh 6.39) tip tc. Cc enzyme transaldolase v transketolase c chuyn ha cho
con ng ny. Nhiu enzyme khc cng s dng trong con ng ng phn hoc s
to thnh glucose (b) s n gin gii thiu con ng bin i t 6 pentose (5C) n 5
hexose (6C).
u tin, ribulose-5- phosphate c bin i thnh xylulose-5- phosphate. Sau , c
s sp xp li ca b xng carbon ca cc hp cht trung gian phosphate- ng. Su ng
phosphate 5 carbon c bin i thnh 5 ng phosphate 6 carbon (hnh 6.40b), hon
thnh chu trnh v cho php tip tc oxy ha glucose 6- phosphate vi s to thnh
NADPH
2
.
Trong phn khng oxy ha ca con ng pentosephosphate (hnh 6.40a),
transketolase, thiamin pyrophosphate ph thuc enzyme, xc tc chuyn mnh 2 carbon (C-1
v C-2) ca xylulose 5- phosphate thnh ribose-5- phosphate, to thnh sn phm 7 carbon l
sedoheptulose-7- phosphate; mnh 3 carbon ca xylulose b loi l glyceraldehyde-3-
phosphate. Sau transaldolase xc tc phn ng tng t i vi phn ng aldolase trong
ng phn v kt hp vi glyceraldehyde-3- phosphate to thnh fructose-6- phosphate; loi
i mnh 4 carbon ca sedoheptulose to nn rythrose-4- phosphate. By gi transketolase li
hot ng, to thnh 6- phosphate v glyceraldehyde-3- phosphate t erythrose-4- phosphate
v xylulose-5- phosphate. Hai phn t glyceraldehyde-3- phosphate to thnh bi 2 tc ng
qua li ca cc phn ng ny c th bin i thnh fructose 1,6-diphosphate (hnh 6.40b).
phc hp chu trnh: 6 pentose phosphate bin i tr li thnh 5 hexose phosphate.
Tt c cc phn ng ca phn khng oxy ho ca con ng pentose phosphate d dng
thun nghch, v vy cng dn n s bin i hexosephosphate thnh pentosephosphate.
5.2.2. Glucose c bin i thnh acid glucoronic v acid ascorbic.
Con ng th yu khc i vi bin i glucose thnh 2 sn phm c bit: D-
glucoronate, quan trng trong s loi c t v s bi tit ca cc hp cht v c bn ngoi v
acid L-ascorbic hoc vitamin C.
Hnh 6.41: Cc con ng th yu i vi s trao i cht glucose qua UDP-
glucuronate.
Trong con ng ny (hnh 6.41) glucose-1 phosphate c bin i u tin thnh
UDP-glucose bi phn ng vi UTP. Phn glucose ca UDP-glucose c kh hydro to
thnh UDP- glucoronate, mt v d khc s dng dn xut UDP nh l nhng cht trung gian
trong s bin i enzyme ca cc ng.
UDP glucoronate l cht cho glucuronosyl s dng bi h enzyme loi c t, n hot
ng trn nhiu thuc khng phn cc, cc c t mi trng v cc cht sinh ung th. S kt
hp ca cc phc cht ny vi glucoronate bin i thnh rt nhiu dn xut phn cc c
loi d dng khi mu bi thn v c bi tit trong nc tiu. V d loi c t ca 3-
hydroxybenzo [ ] pyren, thnh phn c ca khi thuc l (hnh 6.42) hay thuc gim au
phenobarbidal, thuc khng AIDS nh AZT v dng hydroxyl ha ca cht sinh ung th
benzo [] pyren (3-hydroxybenxo pyren) chu s glucuronite ho c xc tc bi UDP-
glucorosyl transferase trong gan ngi. S biu hin i vi pha thuc hoc c t lm tng
s tng hp enzyme c bit i vi pha tng hp lm tng s chng vi thuc hoc khng
i vi c t. UDP-gluconat cng l tin cht ca cc gc glucoronate ca cc acid
polysaccharide c tnh acid nh hyaluronate v chondroidin sulphate.
D- glucoronate l cht trung gian trong s bin i ca D-glucose thnh acid L-ascorbic
(hnh 6.41). N c kh bi NADPH
2
thnh ng 6 carbon l acid L-gulonate, ri c
bin i thnh lactone. Sau L-gulonolactone b kh hydro bi flavoprotein gulonolactone
oxydase thnh acid L-ascorbic. Mt s loi ng vt, k c ngi, chut lang, kh, mt s
chim, v mt s c thiu enzyme gulonolacton oxydase nn khng c kh nng tng hp acid
ascorbic.
Con ngi khng c vitamin C trong thc n lm pht trin bnh hoi huyt
(scocbut) do cc m lin kt b h hng lm chy mu da, sng li rng v.v.. Hng trm nm
trc y thu th cc on thuyn bun rt hay b bnh ny trong nhng chuyn i di ngy
do khng c n hoa qu ti cha nhiu vitamin (trong c vitamin C). Nm 1753 bc s
phu thut hi qun James Lind ngi Scotland cho bit cch cha bnh hoi huyt
(Scocbut) bng nc cam. Nm 1932 cht chng li bnh hoi huyt (Scocbut) l vitamin C
c tch t nc chanh v c gi l acid ascorbic (ting Latinh Scorbutus ngha l
sng ty l lot).
Hnh 6.42. S loi c t 3- hydroxybenzo
[ ] pyren(thnh phn c ca khi thuc l). S
glucuronide ha bi s chuyn glucuronate thnh
UDP- glucuronate bin i c t khng phn cc
thnh phc hp phn cc d dng b loi b bi
thn.
5.2.3. Chu trnh Glyoxylate
Qu trnh bin i phosphoenolpyruvate thnh pyruvate v pyruvate thnh acetyl-CoA
l qu trnh khng o ngc v c hai u l qu trnh gii phng nng lng.
Phosphoenolpyruvate c th c tng hp t oxaloacetate trong phn ng ngc c
xc tc bi cacboxykinase.
Oxalo acetate + GTP phosphoenolpyruvate + CO
2
+ GDP
Hnh 6.43a: Chu trnh glyoxylate v quan h ca n vi chu trnh acid citric.
Cc nguyn t carbon t cc phn t acetate i vo chu trnh acid citric khng th bin
i trc tip thnh oxaloacetate v chng ra khi chu trnh di dng 2 phn t CO
2
, nn
acetate khng th bin i ngc v phosphoenolpyruvate tng hp ng glucose.
thc vt v mt s vi sinh vt nh E.coli v nm men, acetate c th c c 2 vai tr:
cung cp nng lng v nh mt ngun phosphoenolpyruvate cho tng hp carbonhydrate.
Nhng sinh vt ny c mt chu trnh glyoxylate bin i acetate thnh oxaloacetate. nhng
sinh vt ny, mt s enzyme ca chu trnh acid citric ng thi xc tc c 2 qu trnh (1) oxy
ha acetyl-CoA thnh CO
2
, xy ra hu ht cc m, v (2) chu trnh glyoxylate. Chu trnh
glyoxylate l bin dng ca chu trnh acid citric (hnh 6.43a,b).
2 AcetylCoA + NAD
+
+ 2H
2
O Succinate + 2CoA + NADH + H
+
Ch rng chu trnh glyoxylate b qua 2 phn ng decarboxyl ha ca chu trnh acid
citric v 2 phn t acetyl-CoA i vo chu trnh glyoxylate mi chu trnh nhng ch c mt
phn t acetyl-CoA i vo chu trnh acid citric. thc vt, cc enzyme ca chu trnh
glyoxylate to thnh cm gn vo mng glyoxysome ca mt bo quan thng.
Hnh 6.43b: Chu trnh glyoxylate v quan h ca n vi chu trnh acid citric.
Hnh 6.44. Cc phn ng ca chu trnh glyoxylate ( glyoxysome) tng ng vi
cc phn ng ca chu trnh acid citric ( ty th), cc cht trung gian thng qua
phn cht tan gia cc ngn
Hnh 6.45. Qu
trnh iu ha hot
tnh isocitrate
dehydrogenase xc
nh s phn b ca
isocitrate gia chu
trnh glyoxylate v
chu trnh acid citric.
Khi isocitrate
dehydrogenase b
mt hot tnh do
qu trnh
phosphoryl ha (bi
mt protein kinase
c hiu), isocitrate
i vo cc phn ng
sinh tng hp qua
chu trnh glyoxylate,
cn khi enzyme
c hot ha nh
qu trnh kh
carboxyl ha (bi
mt phosphatease
c hiu), isocitrate
i vo chu trnh
acid citric v kt
qu l to ATP.
Cc enzyme ny xc tc chung cho c chu trnh acid citric v glyoxylate c 2 dng ng
phn, mt c hiu vi ty th v dng kia c hiu vi glyoxysome. Glyoxysome khng phi
lc no cng c mt mi m thc vt m chng xut hin nhiu nht ht giu cht bo
trong qu trnh ny mm, trc khi mm, cy ln c th t to carbonhydrate thng qua
qu trnh quang hp. V vy glyoxysome c mt cc enzyme xc tc qu trnh phn gii
acid bo d tr trong ht thnh acetyl-CoA v bin i thnh malate qua chu trnh glyoxylate.
Malate sau bin i thnh malate oxaloacetate v glucose (hnh 6.44).
Aspartate mang b khung carbon ca oxaloacetate t chu trnh acid citric ( ty th) ti
glyoxysome, ni n kt hp vi acetyl-CoA t s phn hu acid bo. Citrate v vy to thnh
isocitrate nh aconitase, sau phn gia thnh succinate nh isocitrate lyase. Succinate quay
li ty th, ni n i vo chu trnh acid citric v chuyn thnh oxaloacetate c th li ti
glyoxysome. Glyoxylate c to thnh pha trong glyoxysome kt hp vi acetyl-CoA
to thnh malate i vo phn cht tan v oxy ha (nh malate dehydrogenase t bo) thnh
oxaloacetate, tin cht ca glucose qua qu trnh to glucose. Bn con ng khc nhau tham
gia vo cc qu trnh chuyn ha ny: acid bo b phn hu thnh acetyl-CoA (
glyoxysome), chu trnh glyoxylate ( glyoxysome), chu trnh acid citric ( ty th) v qu trnh
to glucose ( phn cht tan). S tham gia ca cc cht trung gian cn cc con ng iu
ha v phi hp ny. Isocitrate l mt cht trung gian rt quan trng, nm nhnh gia chu
trnh glyoxylate v chu trnh acid citric (hnh 6.45).
6. S iu ho qu trnh trao i glucid
Trong c th ng vt c hai h thng c tc dng iu ho qu trnh trao i vt cht
l thn kinh v hormone. Trao i vt cht l mt qu trnh thng nht, nhng bin i
trong qu trnh trao i glucid u nh hng v tc ng n qu trnh trao i cht ni
chung nh trao i protein, trao i lipid... v ngc li. Tuy vy mi qu trnh trao i cng
c nt c th ring ca n. i vi trao i ng, mu l cu thng bng hm lng ng
gia gan v cc c quan. Hm lng ng trong mu thng n nh cc loi gia sc, iu
ny c mt ngha quan trng i vi vic duy tr p sut thm thu ca mu vi m bo.
mt c th c trao i glucid bnh thng th hm lng ng trong mu dao ng trong mt
phm vi nht nh gi l hng s ho sinh c th nh ngi l 80-120mg%; Ln, ch, mo
l 80-120mg%; gia cm 150-300 mg%; tru b 45-70mg%; nga 70-150mg%. Khi ng vt
n nhiu ng, s tha s bin thnh glycogen d tr gan, c, khi cc m bo cn ti th
loi ng ny li c huy ng s dng. C ngha l nu hm lng ng vt qu
khong dao ng ti thiu, ti a th thn kinh v th dch s iu ho lm cho n v
khong dao ng .
6.1.V thn kinh
No ca ng vt ch yu dng glucose lm ngun nng lng. Trong iu kin bnh
thng 1/4 lng ng dng cho no, bt c mt s gim hm lng ng no trong mu
u nh hng ngay ti no, no rt nhy cm vi hm lng ng trong mu. Thng cc
trng thi hng phn lm hm lng ng trong mu tng. y bung no 4 c mt trung
tm thn kinh cm th c hm lng ng trong mu. T khi hm lng ng trong
mu thay i n s pht tn hiu n cc b phn iu chnh, trc ht l ti vng di i
(hypothalamus) ri t tn hiu xung tuyn yn, t tuyn yn s i ti hai i tng tc
ng chnh l tuyn thng thn v tuyn tu ( o Landexhan).
6.2.V th dch
Tuyn tu o Landexhan c t bo sn sinh ra Insuline v t bo sn sinh ra
glucagon, y l hai hormone ca tuyn tu iu ho hm lng ng trong mu.
Insuline tit ra hng ngy khong 10-25mg, nhiu gp 5 ln nhu cu, khi mi tit ra
di dng proInsuline cha c hot tnh. ProInsuline gm 3 chui: Chui A gm 21 acid
amin, chui B gm 30 acid amin, gia 2 chui ny c 2 cu ni disulfid. chui A c 1 cu
disulfid. Gia chui A v B l chui C. Chui C gm c 30 acid amin, n c ni vi chui
A v B bi 2 cp acid amin kim tnh (arg.arg v arg.Lyz). Khi c nhu cu v Insuline n
c enzyme peptinase ct b chui C v to thnh Insuline c hot tnh. Insuline nhng
ng vt khc nhau th khc nhau ch yu chui A v tp trung vo cc acid amin 8,9,10, 12
v 14, cn chui B hu nh ging nhau, khc nhau ch yu acid amin 30. Do c th dng
khc loi song hiu qu khng cao. Khi tit ra mu Insuline c vn chuyn vi 1 protein
v mt phn vi mng ca hng cu.
Sau khi hot ng xong Insuline c phn hu bi Insulinease, enzyme ny c nhiu
gan. Tc dng ca Insuline l lm gim hm lng ng trong mu khi hm lng ny vt
qu mc dao ng ti a.
V c ch tc dng ca Insuline: ngi ta thy y l loi hormone c tc dng rt rng
ri, a dng, n lm cho t bo lipid, c tng cng s hp thu ng tng hp lipid,
glycogen. Khi c mt ca Insuline th cc qu trnh vn chuyn ng qua mng t bo c
tng cng v tng cng qu trnh phosphoryl ho ng, t glucose i vo cc con
ng tng hp. Mt enzyme chu tc ng r rt nht ca Insuline l hexokinase lm hot
ho ng, thng qua con ng ny glucose i vo qu trnh phn gii to nng lng cho t
bo ca c th. Mt khc Insuline c tc dng ngn cn s hot ng ca nhm corticosteroid
(hormone sinh mi glucose), ng thi n c ch enzyme adenylatcyclase, ngn cn s
chuyn ho glycogen thnh glucose. Vi nhng tc ng trn hm lng ng trong mu s
gim.
Glucogon l mt chui peptide 29 acid amin. do t bo ca o Landexhan tit ra,
n l mt polipeptide gm 29 gc acid amin. Khi mi tit ra dng proglucagon khng c
hot tnh c thm 8 gc acid amin u COOH, tc l c 37 acid amin. Trc khi vo
mu n t ct b 8 gc acid amin ny v tr thnh glucagon c hot tnh.
Glucagon c tc ng i khng vi Insuline lm tng hm lng ng trong mu. C
ch tc ng ca n ging nh Adrenalin l hot ho h thng enzyme protein-kinase thng
qua 3
'
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'
-AMP vng, h thng enzyme ny c tc dng phn gii glycogen thnh glucose. Tuy
nhin n ch pht huy tc dng gan, khng c tc dng c.
Tuyn thng thn: Tit ra Adrenalin, nor Adrenalin v corticosteroid.
Adrenalin v Nor adrenalin: Khi hm lng glucose trong mu gim xung th tn
hiu c truyn n min tu thng thn, y tit ra Adrenalin v Nor adrenalin, chng
c tc dng lm tng hm lng ng trong mu.
C ch tc ng ca chng l hot ho h thng enzyme protein kinase thng qua 3
'
-5
'
-
AMP vng, nh tc ng ln enzyme adenylatcyclase nm ti im cm th ca chng trn
mng t bo (xem phn c ch tc dng ca hormone). c im ca chng l vi liu rt nh
(hm lng trong mu khong 10m) nhng hiu qu tc dng rt ln, chng pht huy tc
dng c gan v c. c qu trnh phn gii glycogen ch n glucose-6P, glucose-6P s i
vo con ng oxy ho ngay, khng thnh glucose. Hot lc ca Adrenalin cao hn so vi
Nor adrenalin. Ngoi ra Adrenalin cn c tc dng lm tng cng co bp ca tim, lm tng
tun hon mu. Tt c cc hin tng hng phn, hi hp, stress u gy tit Adrenalin v
lm tng hm lng ng trong mu.
Nhm corticosteroid do min v thng thn tit ra, y l nhm hormone sinh mi
glucose (glucose c sinh ra t protein, lipid). Di tc dng ca nhm hormone ny qu
trnh phn gii acid amin c y mnh, bin acid amin thnh cc cetoacid, t cc cetoacid
ny chuyn ho thnh ng
Protease Oxydase
Protein --------- > Acid amin -------- > NH
3
+ ceto acid (pyruvic, oxaloaxetic, -ceto glutamic)
-------- > glucose.
Corticosteroid c tc dng hot ho cc enzyme trn.
Ngoi ra mt s hormone nh Thyroxin ca tuyn gip trng lm tng cng qu trnh
oxy ho t cng lm gim hm lng ng trong mu.
6.3. Cc enzyme iu ho hot ng nh nhng van iu chnh trao i ng.
Qu trnh d ha saccharide cung cp ATP v cc tin cht cho cc qu trnh sinh tng
hp khc nhau. i vi cc t bo iu quan trng nht l lm sao gi n nh nng ATP
khng thay i. iu ny t c nh s iu ho ca mt s enzyme cha kha chu trch
nhim xc tc mt s phn ng cc giai on quan trng ca qu trnh d ha. Trong qu
trnh ng phn m c v gan c 4 enzyme sau y ng vai tr iu ho: Glycogen
phosphorylase, hexokinase, phosphofructokinase v piruvate kinase.
duy tr s tn ti ca mnh, c th sng lun phi
duy tr trng thi cn bng hot ng ca qu trnh chuyn
ha trao i cht. Do khi xut hin bin ng lm thay
i trng thi trn cc c ch iu ho hot ng sng phi
iu chnh sao cho trng thi ni mi ca c th sng vn
c duy tr. V ATP gi vai tr then cht trong tt c cc
chu trnh tin ha trao i cht ca c th nn trong qu trnh
tin ho v chn lc t nhin xut hin mt s enzyme
iu ho v duy tr s n nh hm lng ATP.
Trong thc t dng vn chuyn cc cht trao i ph
thuc vo hot ca enzyme xc tc cc phn ng trao i
cht. Trong s cc enzyme xc tc ton b mt chu trnh
bin i cht no (nh ng phn chng hn) bao gi
cng c mt s ln enzyme hot ng trng thi cn bng. Cc enzyme ny c hot tnh rt
cao, c th bin i c cht va c chuyn n thnh sn phm ca phn ng, ngha l tc
dng trao i cht giai on phn ng bin i ch b gii hn bi c cht v c xc
nh bi hm lng c cht thi im ni trn. Tuy nhin khng phi ton b cc phn ng
u c xc tc nh vy. S thc trong bt c chu trnh bin i vt cht no trong c th
sng cng c mt s phn ng hot ng trng thi rt xa trng thi cn bng. V d, trong
qu trnh ng phn hng s cn bng Keq ca phn ng do enzyme phosphofructose
kinase 1 xc tc c gi tr khong 250. Trong khi t l khi lng tc ng (fructose-1,6-
diphosphate [ADP]/ [fructose6-phossphat][ATP]) ca phn ng li rt nh khong 0,04.
S d phn ng trn rt xa v tr cn bng v tc bin i fructose-6-phosphate
thnh fructose-1,6-diphosphate b gii hn bi hot tnh ca enzyme xc tc. Do d c gia
tng dng fructose-6-phosphate do cc phn ng trc to ra, th tc ca phn ng trn
vn khng thay i ng k. iu ny c ngha l enzyme phosphofructokinase-1 hot ng
nh van iu khin ton b dng vn chuyn trao i cht ca qu trnh ng phn. Theo
quy lut chung th trong bt k chu trnh chuyn ha no cng phi c t nht 1 phn ng giai
on c xc tc bi enzyme iu ho, c hot tnh xc tc ch yu, hot ng trng thi
cn bng. Phn ng ny c gi l phn ng b gii hn bi enzyme khc vi cc phn ng
bnh thng khc b gii hn bi c cht v giai on phn ng ny chnh l giai on gii
hn tc ca ton b qu trnh. Thng thng cc phn ng gii hn u l cc phn ng
pht nhit ch xy ra theo mt chiu. Chng thng c xc tc bi enzyme iu ho d lp
th (allosteric enzyme) v thng phn ng u tin ca lin kt chuyn ha. Th d, trong
qu trnh ng phn glucose-6-phossphate c th chuyn ha theo ng phn do enzyme
phosphofructokinase-1 xc tc hoc chuyn ha theo chu trnh pentose phosphate do enzyme
glucose-6-phospshate dehydrogenase xc tc v theo quy lut c 2 enzyme ny u l enzyme
iu ho.
V tng th, hai qu trnh c xu th tri ngc nhau l qu trnh d ha v ng ha li
lun tn ti trng thi cn bng thng nht v hp l. Trong rt nhiu phn ng ca c
hai qu trnh c xc tc bi cng mt enzyme. Tuy nhin cc hot ng sng c duy
tr n nh, v nguyn tc hai qu trnh trn phi c nh hng r rng. Do trong mi qu
trnh phi c t nht mt phn ng giai on c xc tc bi hai enzyme khc nhau. Cc
enzyme ny chnh l nhng enzyme iu ho hng phn ng ca tng qu trnh v phn ln
cc phn ng do chng xc tc l phn ng to nhit ch xy ra 1 chiu v chng u l cc
phn ng b gii hn bi enzyme ch khng phi c cht.
7. Mt s bnh do ri lon trao i ng
7.1. Bnh cao ng huyt (Hyper glycemia):
Khi mc glucose ca mu vt qu mc ti a th c th gp trng thi cao ng
huyt. Trng thi ny thng dn ti hin tng bi tit ng theo nc tiu, gi l chng
ng niu (glucoguria). Hm lng ng huyt cao c 2 nguyn nhn:
Do thc n: Thc n c nhiu ng, hin tng ny khng nguy him. a s ng
vt v ngi khi hm lng ng trong mu ti 160mg% th kh nng hp thu ng ca
gan b ht, t bo thn ( ng ln xa) cng khng sc thm thu tr li glucose ( t
ti mol thm thu), do nc tiu xut hin ng. Hin tng ng niu thc phm
thng chng qua khi.
Do bnh ng niu (Dia betes mellitus): y l hi chng phc tp ca trao i
ng. Nguyn nhn trc tip l do thiu Insuline. Trong c th ng vt gia cc hormone
c s cn bng tc ng vi nhau, khi thiu hormone ny th hormone i khng s tc ng
mt mnh, do lm mt cn bng trao i cht. Khi thiu Insuline lm hm lng ng
trong mu c th t ti 300-500mg% v trong mt lt nc tiu c th c t 8-10g ng.
Khi thiu Insuline s lm gim thm thu glucose ca t bo, lm yu hot tnh ca
enzyme hexokinase, do lm cho s tiu th glucose ca t bo b hn ch (tr hng cu v
t bo thn kinh l khng chu nh hng ca Insuline). Nh vy trong mu tha ng m t
bo li thiu nng lng, t bo phi dng lipid lm nguyn liu, lipid dng nhiu gy nn th
ceton huyt, ceton niu, iu ny cng lm cho s chuyn ho b ri lon. Mt khc thiu
Insuline lm cho qu trnh chuyn ho acid amin. thnh glucose cng y mnh v c th b
gy mn nhanh chng. Bnh thiu Insuline thng l chc nng ca tuyn tu b h nh b
vim...
7.2. Bnh thp ng huyt (Hypo glycemia)
Bnh thp ng huyt l trng hp lng ng trong mu nm di mc ti thiu.
Hin tng ny thng gp trong trng hp thiu nng tuyn thng thn, gy thiu
Adrenalin hoc mt s ng vt cha k cui, ln s sinh.
7.3. Ri lon trao i ng do thiu vitamin
Trao i glucid l mt qu trnh phc tp, c rt nhiu enzyme tham gia, c bit l
cc enzyme kh carboxyl i vi cc cetoacid nh pyruvic, -cetoglutamic... cc phn ng
ny u cn enzyme c nhm ghp l TPP l dn xut ca VTM B
1
, do vy khi thiu VTM B
1
cc phn ng trn s khng thc hin c, acid pyruvic khng c kh b ng li n
phn ly nh hng ti pH ca t bo dn n hin tng tch nc gy nn ph (bnh
Beriberi). Acetyl CoA khng c hnh thnh gy thiu Acetylcolin l cht dn truyn xung
ng xinap thn kinh gy nn vim thn kinh, au u...
CHNG VI: GLUCID V TRAO I GLUCID
Khi nim v vai tr ca glucid. S tiu ho v hp thu tinh bt. Tiu ho cht
s loi nhai li. S tng hp, phn gii glycogen. S chuyn ho trung gian ca
glucose. S oxy ho glucose trong iu kin c oxy. S iu ho trao i glucid.
Mt s bnh do ri lon trong trao i glucid.

Cu 1: Qu trnh tng hp Glycogen? Nhng hormon iu khin qu trnh ny? Cu
2: Qu trnh phn gii Glycogen? Nhng hormon iu khin qu trnh ny? Cu 3:
Qu trnh ng phn m bo ng vt? ngha ca qu trnh ny? S ging v
khc nhau gia qu trnh ng phn v qu trnh ln men.
Cu 4: Vng Cori v ngha ca n?
Cu 5: S chuyn ho ca glucose trong iu kin c xy? Qu trnh chuyn ho t
axit pyruvic thnh acetylCoA
Cu 6: Vng Krebs v vai tr sinh hc ca n trong trao i vt cht?
Cu 7: Mt s bnh do ri lon trao i ng?
CHNG VII
LIPID V S CHUYN HO LIPID
1. i cng v lipid
1.1. Khi nim v lipid
Lipid l nhng hp cht hu c ph bin trong t nhin cng nh trong c th ng vt,
thc vt v vi sinh vt. Lipid c c tnh khng ho tan trong nc, ch ho tan trong cc dung
mi hu c nh cn, ete, cloroform, benzen, aceton v.v.. Khng phi mi lipid u ho tan
nh nhau trong tt c cc dung mi ni trn m mi lipid ho tan trong dung mi tng ng
ca mnh, nh c tnh ny ngi ta c th phn tch ring tng loi.
Tn gi lipid bt ngun t ch Hy lp lipos l m dng ch chung cc loi lipid, du
v cc cht bo ging m ng vt v du thc vt. V mt ho hc lipid l nhng este
gia ru v acid bo, in hnh l cht Triacylglycerol.
CH
2
- O CO R
1

CH- O CO R
2

CH
2
- O CO R
3
Tu theo thnh phn cc acid bo v ru khc nhau m c cc lipid khc nhau, thc
vt v vi sinh vt s phong ph v cc acid bo thng cao hn ng vt c v
Mt s acid bo thng gp:
Tn gi Cng thc Ni c nhiu
acid butyric
acid caproic
acid caprylic
acid capric
acid lauric
acid myristic
acid palmidic
acid stecaric
acid arachidic
CH
3
(CH
2
)
2
COOH
CH
3
(CH
2
)
4
COOH
CH
3
(CH
2
)
6
COOH
CH
3
(CH
2
)
8
COOH
CH
3
(CH
2
)
10
COOH
CH
3
(CH
2
)
12
COOH
CH
3
(CH
2
)
14
COOH
CH
3
(CH
2
)
16
COOH
CH
3
(CH
2
)
18
COOH
Lipid sa (b)
B, da
B, da, no c
Da, no c voi
Du thc vt
Lipid ng vt, du thc vt
-nt-
-nt-
Du lc
Ngoi ru v cc acid bo cc lipid phc tp (lipoid) trong phn t ca chng cn
cha cc dn xut c phospho, nit, sulfur v.v. nh nhm phosphateide, xerebrozid. y l
hai nhm lipid c vai tr quan trng.
Phosphateide c nhiu trong no, dy thn kinh v cc c quan nh gan, tim, thn v
mt s vt phm nh lng trng, sa. Cc i din ca phosphateide thng dng lin
kt vi protein trong lipoprotein ca vch t bo v ca ni kh qun t bo cht.
Xerebrozid l nhm lipoid khng cha acid phosphoric, c nhiu trong no. Thnh phn
ca n ngoi ru, acid bo cn c amin, ng galactose v lu hunh.
thc vt kh nng t tng hp cc acid bo thng phong ph hn ng vt, nht
l mt s acid bo gi vai tr quan trng nh:
Acid linoleic (18C c 2 lin kt kp) C
18
H
32
O
2
CH
3
(CH
2
)
4
CH = CH CH
2
CH = CH (CH
2
)
7
COOH
Acid linolenic (18C c 3 lin kt kp) C
18
H
30
O
2
CH
3
CH
2
CH = CH CH
2
CH = CH CH
2
CH = CH- (CH
2
)
7
- COOH
Acid arachidonic (20C c 4 lin kt kp) C
20
H
32
O
2
CH
3
(CH
2
)
4
CH = CH CH
2
CH=CH CH
2
CH=CHCH
2
CH=CH-(CH
2
)
3
COOH

Nhng loi acid bo ny i vi c th ng vt gi l lipid cn thit, v cn c gi
l vitamin F, chng c tc dng quan trng trong qu trnh sinh trng v pht trin ca m
bo, gip cho qu trnh phn bo.
1.2. Vai tr ca lipid
Lipid i vi c th sinh vt c nhiu ngha quan trng, n c cc vai tr sau:
Lipid l cht d tr nng lng tit kim th tch nht, khi xi ho 1 g lipid c th thu
c 9,3 kilo calo. em so vi lng calo ca 1gam ng hoc protein (4,1 kilo calo/1g) th
lng calo sn ra ca lipid nhiu gp i. Nhu cu nng lng hng ngy ca ng vt do
lipid cung cp khong 30% n 40% hoc hn na tu loi ng vt v trng thi sinh l ca
c th.
Chc nng quan trng nht ca lipid l cu to mng sinh hc (mng t bo, mng ti lp
th v.v.). Trong mng sinh hc, lipid trng thi lin kt vi protein to thnh hp cht
lipoprotein. Chnh nh tnh cht ca hp cht ny to cho mng sinh hc c c tnh
thm thu chn lc, tnh cch in. l nhng thuc tnh ht sc quan trng ca mng t
bo, mng cc c quan t ca n.
Lipid di da ca ng vt c tc dng gi m v gi m cho c th nh tnh m, dn
nhit km.
Lipid l dung mi cho nhiu vitamin quan trng nh vitamin A,E,D,K (nhm vitamin
ho tan trong lipid) v th nu khu phn thiu lipid lu ngy th ng vt d mc bnh thiu
cc vitamin k trn.
i vi loi ng vt ng ng, ng vt di c, cc loi su kn, lipid cn l ngun
cung cp nc, v khi oxy ho 100g lipid c 107g nc sinh ra.
Vic nghin cu s chuyn ho lipid s cung cp cho ta nhng hiu bit v qu trnh v
bo gia sc, qu trnh ci to lm tng hm lng b trong sa, qu trnh tch lu du thc
vt v.v. ng thi nhng hiu bit ny cng gii thch c cc trng thi bnh l nh ceton-
huyt, ceton-niu, gan nhim m v.v. gia sc.
2. Mt s dc im v tiu ho, hp thu, chuyn vn v d tr lipid ng vt.
2.1. S tiu ho lipid.
Do c tnh khng ho tan trong nc, m qu trnh tiu ho lipid li c bn cht l qu
trnh thu phn, enzyme thc hin qu trnh ny l enzyme esterase (lipase) nn s tiu ho v
hp thu lipid c mt s nt c th ring. Mun cho enzyme phn gii c th lipid phi
trng thi nh tng ho, tc l trng thi dung dch gi.
ming: khng c enzyme phn gii lipid, y lipid ch chu tc dng c hc do qu
trnh nhai, nho trn thc n.
d dy: i vi ng vt b m (b, ngh, ln con v.v.) trong dch d dy c cha
enzyme lipase, nhng hot lc yu do nh hng ca pH thp, tuy nhin do thc n l sa m,
lipid dng nh tng nn qu trnh phn gii lipid y kh cao. ng vt trng thnh
hu nh d dy khng c qu trnh thu phn lipid.
rut non: y l ni tiu ho chnh cc cht lipid, v y c cc yu t tin
hnh qu trnh ny. Lipid mun c tiu ho phi c nh tng ho, thc cht ca qu
trnh nh tng ho l bin lipid thnh dung dch gi (gi ho tan) lm tng din tch tip
xc ca lipid vi enzyme lipase. Qu trnh nh tng ho lipid rut non nh mt lot cc
yu t sau:
S nhu ng ca rut cng vi trng thi xp ca thc n do kh CO
2
sinh ra trong qu
trnh trung ho HCL ca dch v bi cc bicarbonat ca dch rut.
HCl + NaHCO
3
-----> NaCl + H
2
CO
3
----> CO
2
+ H
2
O
Cc acid mt bao gm: acid cholic, acid 7 Desoxycholic, acid lidocholic, acid
kenodesoxycholic.
OH CH
3
CH
3
CH
CH
3
CH
2
CH
2
COOH
HO OH
Acid cholic
OH CH
3
CH
3
CH
CH
3
CH
2
CH
2
COOH
HO
Acid 7 desoxycholic
CH
3
CH
3
CH
CH
3
CH
2
CH
2
COOH
HO
Acid litocholic
CH
3
CH
3
CH
CH
3
CH
2
CH
2
COOH
HO OH
Acid kenodesoxycholic
Cc acid mt c hnh thnh t cholesterol, qu trnh ny din ra t bo gan, sau
c tit ra ng mt ri vo ti mt. Trc khi vo rut non, n c lin kt vi
glycine v taurin to thnh acid glycocholic v acid taurocholic.
Cc hp cht ny c tnh phn cc v hot tnh b mt, do di tc dng nhu ng
ca rut, lipid b v thnh cc ht nh, cc ht lipid nh ny c ph bi lp acid mt v lp
v thu ho nn khng th kt hp vi nhau c na. Qu trnh ny c tip tc, lipid b v
thnh cc ht nh li ti, l dng nh tng, to iu kin cho enzyme lipase hot ng.
Ngoi tc dng nh tng ho lipid, acid mt cn c vai tr hot ho enzyme lipase v
cn cho qu trnh hp thu acid bo v lipid qua mng t bo rut.
Enzyme lipase t trng c hai ngun gc: lipase do tuyn tu tit ra l ch yu v
lipase do nim mc rut non tit ra. Lipase khi mi tit ra cn dng zymogen, sau khi gp
acid mt mi chuyn sang trng thi hot ho. Di tc dng ca lipase, lipid c phn gii
thnh glycerine v cc acid bo theo phn ng sau:
CH
2
- O CO R
1
+ 3H
2
O CH
2
OH R
1
COOH
---------->
CH
2
- O CO R
2
Lipase

CH OH + R
2
COOH

CH
2
- O CO R
3
CH
2
OH R
3
COOH
Lipid Glycerine Cc acid bo
Qu trnh phn gii lipid vi mc khc nhau, nn cc sn phm to ra c th l
diglyxeride, monoglyceride, cc acid bo v glycerine.
CH
2
-OCOR
1

CH
2
-OCOR
2

CH
2
-OCOR
3
Triglyxeride
CH
2
- OH

CH - O - CO - R
2

CH
2
-OCOR
3
Diglyxeride
CH
2
-OH

CH
2
-OCOR
2+
CH
2
-OH
Monoglyxeride
CH
2
- OH
CH- OH
CH
2
- OH
Glycerine

Thm ch cn c c nhng ht lipid nh 1/100. Tt c nhng sn phm ny u c hp thu
qua vch rut.
2.2. S hp thu, d tr v vn chuyn lipid
i vi glycerine v tnh ho tan trong nc nn d dng c hp thu vo t bo nim mc rut.
i vi cc acid bo khng ho tan trong nc, nn mun c hp thu n phi c
lin kt vi acid mt to thnh phc cht gi l acid choleic ho tan v c hp thu qua t
bo vch rut hoc th ng hoc theo nguyn tc m bo. S hp thu theo nguyn tc m
bo l ch yu.
Sau khi vo t bo vch rut, acid mt tch khi acid bo. Acid mt i vo h tnh mch
tr v gan. t bo vch rut, acid bo c th kt hp vi glycerine ti to thnh lipid. 70-
80% lipid ti to ny i vo ng lm ba di dng nhng ht to nh khc nhau c tn l
Chylomicron, n c mt lp v protein, trong l cc acid bo, triglycerid, cholesterol y
l dng ho tan trong nc nn d vn chuyn dch lm ba v mu.
Nhng sn phm trn i qua t bo vch rut vo ng lm ba, cng theo hnh thc
m bo. Mt phn rt nh (10-15%) acid bo phn t nh v lipid i vo tnh mch.
T ng lm ba ct cc sn phm trn i theo ng lm ba ln lm ba ngc. T
vo h tun hon (h tnh mch) v gan v t gan i ti cc m m. Sau tu theo nhu cu
v nng lng, lipid li c a ti cc c quan cn oxy ho hoc c tch lu li thnh m
d tr. Bng phng php nguyn t nh du, ngi ta thy rng bt c loi lipid no trc
khi em s dng vo cc nhu cu ca c th u tri qua giai on tch lu khong 3-5 ngy.
Qua ta thy m m khng phi l loi m tnh ti m ngc li n lun thay i.
T m m, acid bo v glycerine c gii phng nh enzyme lipase c th ca m.
ng ch l loi enzyme lipase ny chu nh hng tc ng iu tit ca nhiu loi
hormone. Cc acid bo v glycerine t m m c a vo mu, vn chuyn di dng
lin kt vi albumin v mt phn vi -globuline ti cc m bo cn s dng (dng phc hp
c t trng cao v t trng thp ( HDLP v LDLP). C quan s dng acid bo nhiu nht l
gan v mt phn l c tim.
2.3. Vai tr ca gan ng vt trong chuyn ho lipid:
Trong qu trnh chuyn ho lipid gan ca ng vt gi mt vai tr ht sc quan trng.
Gan l c quan sn sinh ra cc acid mt, l yu t nh tng ho m v hot ho lipase. V
vy, khi qu trnh tit mt km, s tiu ho v hp thu lipid s b nh tr. Lipid khng c
tiu ho s theo phn ra ngoi. Acid mt cn gi vai tr trong qu trnh hp thu acid bo, nn
thiu acid mt s nh hng ti qu trnh ny.
Ngoi vic sn sinh ra cc acid mt gip cho qu trnh tiu ho v hp thu lipid, gan
cn l c quan chuyn ho lipid ch yu ca c th ng vt. Hu ht cc m bo ca c th
ng vt u c kh nng dng lipid vo nhu cu nng lng, nhng ch yu di dng cc
sn phm ca lipid c ch bin gan.
3. S phn gii triglyceride
Trong iu kin trao i cht bnh thng, c th ng vt s dng 30-40% nng lng
cung cp t lipid cn 60-70% do glucose. Tuy nhin, do d tr glucid m khng ln, nn
trong nhng trng hp nh khi i, khi lao ng cng thng hoc mt vi trng thi sinh l
c th nh ng vt ng ng, chim c di c theo ma v.v. th ch yu dng nng lng t
lipid. Thng s h hp cho phn ho lipid tng i thp, v qu trnh ny i hi nhiu oxy.
RQ = CO
2
: O
2
= 0,71
H thng enzyme chuyn ho lipid gan ca ng vt kh cao. Hng ngy c mt
lng lipid nht nh c chuyn t cc m d tr a v gan v c x ch gan trc
khi a i cc m bo khc s dng. c bit khi c th thiu glucid (c th do dinh dng,
do trng thi sinh l hoc bnh l v.v.) th lng lipid gan tng ln r rt. Nu t bo gan
khng oxy ho tt do cc nguyn nhn bnh l, lipid s ng gan gy tnh trng gan
nhim m.
T m m, acid bo v glycerine c gii phng nh tc dng ca enzyme lipase c
th ca m. Glycerine c a ti cc m bo s dng ngay, cn cc acid bo c a v
gan x ch trc khi i ti cc m s dng. Qu trnh phn gii nh sau:
3.1. S chuyn ho trung gian ca glycerol
Glycerine l sn phm rt d chuyn ho trong c th, n chuyn thnh glycerine
aldehydeyd theo x phn ng sau:
Glycerine Glycerophosphate Phosphoglycerine aldehyt
Phospho - glycerine aldehyt i vo con ng ng phn.
3.2. S chuyn ho ca acid bo
gan, h thng enzyme oxy ho acid bo hot ng rt mnh. Mt acid bo mun
c oxi ho phi tri qua mt s bc sau:
3.2.1. Hot ho acid bo: Acid bo vo t bo gan, t bo cht n c hot ho bi
h thng enzyme Acyl-CoA-Syntetase hot ho gm 2 bc:
AMP c gii phng t phn ng (2) s c phosphoryl ho tr li thnh ADP di
tc dng ca Adenylate Kinase:
2ADP AMP +
ATP

Vy thc cht qu trnh hot ho mt phn t acid bo t do s dng 2ATP.
Phn ng tng qut c th vit:
R COOH + 2ATP +
CoASH
AcylCoA sylthetase
AcylCoA
PP
+ 2ADP +
Enzyme AcylCoA synthetase cn gi l thiokinase c nhiu mng ngoi ty th v h
thng li ni bo. C nhiu loi acylCoA synthetase c hiu vi cc acid bo lin kt ngn,
trung bnh v di. Qu trnh ny c thc hin ngoi bo tng.
3.2.2. Vn chuyn acid bo vo trong ty th.
Cc acid bo lin kt ngn (4-10C) qua mng ty th d dng. Nhng cc acid bo lin
kt di (t 12 C tr ln) c vn chuyn qua mng ty th nh h thng Carnitin do enzyme
Carnitin acyl transferase (CAT) thc hin.
Carnitin l mt amin bc bn mang mt chc alcol bc 2, c nhiu trong c v gan.
Carnitin c th ester ho vi acid bo nh s xc tc ca Carnitin acyl transferase I c trong
mng ngoi ty th to thnh Acyl carnitin v gii phng CoASH.

Bc tip theo, gc acyl trong Acyl carnitin c chuy n CoenzymeA c bn
trong cht nn ca ty th, y di tc dng ca enzyme Carnitin acyl transferase II to tr
li acylCoA v gii phng Carnitin ( Hnh 7.1)
Acyl Carnitin + CoASH --------------------> Acyl CoA + Carnitin
Carnitin c th coi l cht vn chuyn acyl qua mng ty lp th vo trong cht nn l
ni s din ra qu trnh oxy ho acid bo.
Hnh 7.1. S vn chuyn Acid bo qua mng ty th.
3.2.3. Ti to acyl CoA: Qu trnh ny i ngc li bc 2 v Carnitin c gii phng
tr li mt ngoi ca ty th (hnh 7.1).
3.2.4. Qu trnh - oxy ho acid bo:
Qu trnh c Knoop ngi c (1904) ra trong khi nghin cu v lipid, ng ch
n s carbon chn ca cc acid bo, ng cho rng mun gi c trng thi "chn" th
phn t acid bo ch c th thm hoc bt bi cc sp 2C m thi. Kim chng bng cch cho
ch th nghim n cc acid bo cha s carbon chn v l c nh du bng nhm phenyl.
Trong qu trnh chuyn ho, nhm phenyl khng b ph hu c th tm li trong nc tiu.
Bng cch , ng chng minh c gi thit ca mnh. Ngy nay bng phng php
nguyn t nh du ngi ta kim chng c d dng gi thit ca Knoop. Ngoi qu
trnh - oxy ho, ngi ta cn thy mt s qu trnh oxy ho acid bo khc nh qu trnh -
oxy ho v.v.. Nhng nhng qu trnh ny khng gi vai tr ch yu.
Cc bc ca qu trnh - oxy ho acid bo nh sau:
a) Oxy ho ln1: do enzyme acyl dehydrogenase c nhm ghp l FAD
+
ly i mt cp
H to thnh lin kt i trong enoyl-CoA:
Cp hydro t FADH
2
s c chuyn vo chui h hp to ra 2 ATP
b) Hp nc: do enzyme hydratase, mt phn t nc c ghp vo v tr C

O OH O
|| +H
2
O ||
R CH
2
- CH = CH C SCoA -------------> R- CH
2
- C - CH
2
C SCoA
Hydratase
H
Enoyl - CoA - Oxi Acyl CoA
c) Oxy ho ln 2: Do enzyme acyl dehydrogenase c nhm ghp NAD
+
oxy ho v
tr C
to thnh lin kt ceto acyl CoA

NADH
2
chuyn in t vo chui h hp cho ra 3 ATP.
d) To acetyl-CoA: Do enzyme thiolase gn CoASH vo C
to thnh mt acyl CoA

mi ngn i 2C, v mt acetyl-CoA

O O O O
|| || + CoASH || ||
R CH
2
- C - CH
2
C SCoA -------> R-CH
2
- C SCoA + CH
3
- C SCoA
thiolase
ceto acyl CoA Acyl CoA mi (ngn i 2 C) Acetyl CoA

Qu trnh li lp li, acid bo b ct dn thnh cc acetyl CoA. Mt chu trnh quay ,
t bo thu c 2 cp H
+
: 1 cp cho FAD
+
, 1 cp cho NAD
+
v mt phn t acetyl CoA.
Acetyl CoA i vo chu trnh Krebs oxy ho cho ra nng lng. S chu trnh -
oxy ho acid bo nh sau: ( Hnh 7.2a,b)
Hnh 7.2 a. S qu trnh oxy ho acid bo
Hnh 7.2b. S vng xon Lynen.
Hiu qu nng lng trong qu trnh - oxy ho: v d - oxy ho palmidyl - CoA
(acid palmidic) 16C, t bo thu c ngun nng lng nh sau: c 7 vng quay to ra 7
FADH
2
, 7NADH
2
v 8 phn t acetyl CoA:
7 FADH
2
7 x 2ATP = 14 ATP
7NADH
2

7 x 3ATP = 21 ATP
8 phn t acetyl CoA i vo chu trnh Krebs cho ra 12 ATP x 8 = 96 ATP
Tng cng: 14 ATP + 21 ATP + 96 ATP = 131 ATP
3.2.5. S oxi ho cc acid bo khng no.
i vi cc acid bo c mt hoc nhiu lin kt i, nh acid oleic, acid linoleic... qu
trnh - oxy ho din ra bnh thng, cc phn t acetyl - CoA c tch dn ra, cho ti gn
lin kt i. Ti y, tu theo v tr ca lin kt m cn n s tham gia h tr ca cc
enzyme nh enoyl-isomerase y lin kt i v ng v tr cacbon - v - hydroxyacyl-
epimerase chuyn ng phn D sang dng ng phn L thch ng vi h thng enzym -
oxy ho.
3.2.6. S oxi ho cc acid bo c s cacbon l.
Cc acid bo l cacbon c hnh thnh t s chuyn ho ca cc acid amin nh acid
amin valin, leucin v.v. to thnh acid propionic (CH
3
- CH
2
COOH), acid valeric (CH
3
- CH
2
- CH
2
- CH
2
- COOH). Acid valeric c oxi ho theo con ng - oxy ho ti dng
propionylCoA th dng li. y n c enzym propionyl-carboxylase c nhm ghp l
biotin ghp thm CO
2
vo tr thnh metylmalonyl CoA. Cht ny li c enzym mutase
bin sang dng thng l succinyl CoA. Enzym ny c nhm ghp l dn xut ca VTMB
12
Succinyl-CoA c a vo chu trnh Krebs hoc vo cc chui phn ng chuyn ho
khc v d to vng porphirin, hoc hot ho th ceton c v.v. ( Hnh 7.3).
Hnh 7.3. Qu trnh Carboxyl ho propionyl CoA
4. S hnh thnh v chuyn ho th ceton
Th ceton l tn gi trong chn on lm sng ca nhm gm 3 cht l acid aceto
acetic, acid - hydroxybutyric v aceton
CH
3
- C - CH
2
- COOH CH
3
- CH - CH
2
- COOH CH
3
- C - CH
3
|| | ||
O OH O
Acid aceto acetic Acid - hydroxy butiric Aceton
Trong qu trnh - oxy ho acid bo, lng acetyl CoA c to ra rt nhiu. Bn thn
t bo gan ch s dng mt t acetyl CoA cho nhu cu ca mnh cn phn ln acetyl CoA
c a ti cc m bo khc s dng. Th ceton l dng chuyn vn trung gian ca acetyl
CoA.
Qu trnh to ra th ceton t bo gan nh sau:

O O O
|| - CoASH || ||
a/ 2 CH
3
- C ScoA ------------> CH
3
C CH
2
- C ScoA
AcylCoA Transferase AcetoacetylCoA
O O O
|| || || + H
2
O
b/ CH
3
C CH
2
- C ScoA + CH
3
- C ScoA ------------>
AcetoacetylCoA AcylCoA Syntetase
OH O
| ||
-----> COOH CH
2
C - CH
2
- C ScoA + CoASH
|
CH
3
-hydroxy, - metyl- glutaryl-CoA
OH O O O
| || Phn gii || ||
c/ COOHCH
2
- C - CH
2
- C ScoA -------------> CH
3
C CH
2
- COOH + CH
3
-C ScoA
| Liase
CH
3
-hydroxy, - metyl- glutaryl-CoA Acid acetoaxetic acetylCoA
Acid acetoaxetic sau khi c hnh thnh, c th c enzyme dehydrogenase c nhm
ghp l NADH
2
kh thnh acid -hydroxy butylic.
70-80% th ceton trong mu tn ti dng acid - hydroxy butyric. Trong trng hp
ri lon chuyn ho nng, khi hm lng acid aceto axetic qu cao, mt phn cht ny c th
b mt i CO
2
to thnh aceton (hnh 7.4). Aceton l cht d bay hi c bi tit ra ngoi qua
nc tiu v hi th.
Nh vy, th ceton l nhng cht chuyn ho bnh thng ca c th ng vt, chng
ch tr nn ngun gc gy chng toan huyt khi c sn sinh qu nhiu do iu tit chuyn
ho glucid v lipid b ri lon.
Th ceton c a ti cc m, v d c, v c s dng vo mc ch nng lng
nh bin thnh dng acid aceto acetic hot ng. Qu trnh chuyn ho nh sau:
Acetyl CoA c hnh thnh s i vo chu trnh Krebs (hnh 7.5).

Hnh 7.4. S hnh thnh cc th ceton t acetyl CoA
Hnh 7.5. Qu trnh to acetyl CoA t D- -Hydroxybutyric
thc vt (ht c du) v vi sinh vt, acetyl CoA c th c chuyn ho qua chu trnh
glyoxylate, mt dng ci bin ca chu trnh Krebs, to ra cc sn phm glucid cn cho qu
trnh ny mm.
Qu trnh thnh lp, s dng v bi tit ca th ceton c tm tt nh sau (Hnh 7.6).
Hnh 7.6. S hnh thnh v vn chuyn cc th ceton
5. S tng hp acid bo v triglyceride
Qu trnh tng hp acid bo v lipid l c ch d tr nng lng sinh vt. gia sc
hu ht cc m bo u c kh nng tng hp lipid. Nhng c mt vi c quan c kh nng
tin hnh mnh v thng xuyn nh gan, m lipid v c. Nguyn liu chnh m c th
dng tng hp lipid l nhng sn phm chuyn ho t glucid nh glycerine aldehydeyl-
phosphate, dioxy-aceton-phosphate v acetyl CoA. Cc thc nghim ch r rng ht c du
hm lng lipid tng dn trong khi hm lng glucid gim dn, hai qu trnh din ra song
song v ngc chiu vi nhau. loi nhai li, phn ln lipid cc m, nht l lipid sa c
tng hp t cc acid bo thp phn t nh acid acetic, acid propionic (do qu trnh phn gii
cht x d c cung cp). Gn 50% b ca sa b c to thnh t cc acetate ngm qua
vch d c vo mu ri ti tuyn sa. ln, kh nng s dng glucid to lipid cao hn cc
ng vt khc ti 30%.
Qu trnh tng hp lipid c thc hin bi h thng a enzyme. Trong t bo cc
enzyme ny b tr lin hon vi nhau xung quanh mt protein chnh gia gn vi 6 enzyme
bao quanh protein vn chuyn ng vai tr l cht vn chuyn acyl (ACP-Acyl carrier
protein). Qu trnh tng hp lipid din ra bo tng (li ni bo), qu trnh nh sau:
5.1.Ngun glycerine tc glycerophesphate.
Glycerophosphate c to nn t qu trnh ng phn (t phospho-dioxy-aceton v
phospho-glycerine aldehyde):


CH
2
-O-
H
2
PO
3
C=O
CH
2
-OH
Phosphodioxyaceton

---------->
Isomerase

C HO

CH-OH
CH
2
-O-H
2
PO
3
Phosphoglycerine
aldehyt
+NADH
2
---------->
Dehydrogenase

CH
2
-OH

CH-OH + NAD
CH
2
-O-H
2
PO
3
-glycerophosphate

5.2. Tng hp acid bo theo vng xon Lynen-Wakil:
Acid bo c tng hp t cc phn t acetyl-CoA. Trong qu trnh tng hp, tr phn
t acetyl CoA u tin i vo di dng khng i, cn tt c cc phn t vo sau u t dng
cacboxyl ho tc l malonyl-CoA. Theo Lynen-Wakil qu trnh tng hp acid bo c tin
hnh qua 3 giai on:
5.2.1. Hot ho acetyl CoA to thnh malonyl CoA thc hin bi enzyme carboxylase
c nhm ghp l biotin (cn gi l Vitamin H), ATP v Mn
++
O O
|| ATP ||
CH
3
- C ScoA + CO
2
----------------> COOH - CH
2
- C ScoA
AcetylCoA Mn
2+
, Biotin MalonylCoA

5.2.2. Ni di chui carbon trong acid bo: do enzyme trans acylase:
O SH SH S CO- CH
3
|| | - CoASH | |
CH
3
- C ScoA + EACP SH -------> EACP S CO- CH
3
---> EACP S
AcylCoA
O S CO CH
3
S CO CH
3
|| | - CO
2
|
COOH - CH
2
- C ScoA + EACP SH -------------> EACP S CO- CH
3
MalonylCoA - CoASH
S CO CH
3
SH
| Ngng t |
EACP S CO- CH
3
--------------> EACP S CO- CH
2
CO CH
3
Kh ln 1 do enzyme dehydrogenase c nhm ghp l NADPH
2
Loi nc do enzyme hydratase
SH OH SH
| | - H
2
O |
EACP S CO- CH
2
CH CH
3
--------------> EACP S CO- CH = CH CH
3
Hydratase
Kh ln 2 do enzyme dehydrogenase c nhm ghp l FMNH
2
Phn ng hon nguyn ca FMN
+
FMN
+
+ NADPH
2
-------------> FMNH
2
+ NADP
+
NADPH
2
c to ra t chu trnh pentose phosphate.
Qu trnh li tip tc nhn mt phn t malonyl CoA vo chu trnh v mi vng quay li
ni di thm mt cp carbon ti khi phn t acid bo c di p ng vi phn t acid
bo m t bo cn tng hp (Hnh 7.7).
ACP l mt protein c 77 acid amin c nhm ghp l pantothenic. Cng thc ca
pantothenic nh sau:
CH
3
|
HOCH
2
C CHOH CO NH CH
2
CH
2
COOH
|
CH
3
5.2.3. Kt thc qu trnh tng hp acid bo nh enzyme acyl transferase
SH O SH
| Acyl transferase || |
EACP S CO-(CH
2
)
n
CH
3
+ CoASH ----------------> CH
3
(CH
2
)
n
C ScoA + EACP -
SH

AcylCoA
HOOC CH
2
C SCoA
O
~
C CH
2
C
O O
CH CH
2
C
O
OH
H
3
C
H
C CH C
O
H
3
C
H
2
C CH
2
C SCoA
O
~
CH
3
C SCoA
O
~
HOOC CH
2
C SCoA
O
~
CH
3
CH
3
NADPH2
NADP+
-H2O
FMN+
FMNH2
NADPH2
NADP+
R
H
2
C CH
2
C SCoA
O
~
EACP
SH
SH
Trong c th sinh vt gn 70-80% acid bo ban u c tng hp di dng palmidyl
CoA (16C). Sau , tu theo nhu cu ca t bo, t acid bo ny s c chuyn ho thnh
cc acid bo khc. Vic x l ny c tin hnh hai v tr, nu i hi ni di thm phn t
acid bo th palmidyl CoA c a vo ty lp th, n c ni di bi cc acetyl CoA.
Nu tr thnh cc acid bo khng bo ho hoc thp phn t hn th n c chuyn vo tiu
th microsome oxy ho.
5.3. Qu trnh tng hp m (qu trnh gn acid bo vo glycerine)
Trong t bo c sn glycerine trng thi hot ho. Qu trnh gn acid bo c thc
hin ln lt tng phn t v to thnh cc sn phm: mono, di-glyceride phosphate v cui
cng mi to thnh triglyceride.
Hnh 6.7. M hnh tng hp acid bo theo vng xon Lynen
CH
2
-OH O CH
2
-O - CO - ( CH
2
)
n
- CH
3
|| - CoASH
CH-OH + CH
3
(CH
2
)
n
C ScoA ------------------> CH-OH
Acyl transferase
CH
2
-O-H
2
PO
3
CH
2
-O-H
2
PO
3
Glycerophosphate Mono glyceride phosphate

CH
2
-O-CO - ( CH
2
)
n
- CH
3
O CH
2
-O - CO - ( CH
2
)
n
- CH
3
|| - CoASH
CH-OH + CH
3
(CH
2
)
n
C ScoA -------------> CH-O- CO - ( CH
2
)
n
- CH
3

Acyl transferase
CH
2
-O-H
2
PO
3
CH
2
-O-H
2
PO
3
Mono glyceride phosphate Di glyceride phosphate
CH
2
-O-CO - ( CH
2
)
n
- CH
3
CH
2
-O - CO - ( CH
2
)
n
- CH
3
- H
3
PO
4

CH-O - CO - ( CH
2
)
n
- CH
3
-------------> CH-O- CO - ( CH
2
)
n
- CH
3

Phosphatease
CH
2
-O-H
2
PO
3
CH
2
-OH
Di glyceride phosphate Di glyceride
CH
2
-O-CO - ( CH
2
)
n
- CH
3
CH
2
-O - CO - ( CH
2
)
n
- CH
3
- CoASH
CH-O - CO - ( CH
2
)
n
- CH
3
-------------> CH-O - CO - ( CH
2
)
n
- CH
3

Acyl transferase
CH
2
-OH + CH
3
(CH
2
)
n
C ScoA CH
2
-O-CO (CH
2
)
n
-CH
3.

||
O
Di glyceride Tri glyceride
M hnh thnh c cha vo cc ht trong t bo. ng vt bc cao c 3 acid bo m c th
khng t tng hp c, l:
Acid linoleic (18C c 2 lin kt kp) C
18
H
32
O
2
CH
3
(CH
2
)
4
CH = CH CH
2
CH = CH (CH
2
)
7
COOH
Acid linolenic (18C c 3 lin kt kp) C
18
H
30
O
2
CH
3
CH
2
CH = CH CH
2
CH = CH CH
2
CH = CH- (CH
2
)
7
- COOH
Acid arachidonic (20C c 4 lin kt kp) C
20
H
32
O
2
CH
3
(CH
2
)
4
CH = CH CH
2
CH=CH CH
2
CH=CHCH
2
CH=CH-(CH
2
)
3
COOH

y l ba acid bo gi vai tr quan trng trong qu trnh phn chia t bo (c tn chung
l vitamin F), cc acid bo ny gi l " lipid cn thit", c th ng vt phi khai thc chng
t ngun thc n. Cc acid bo ny tuy nhin li c nhiu du thc vt.
6. S lc v vai tr v s chuyn ho cc dng lipoide
Lipoid gm nhiu i din khc nhau, nhng ngi ta mi nghin cu k hai loi l
nhm Steroid v phospholipid. Hai loi ny tham gia vo nhiu qu trnh trao i vt cht ca
c th.
6.1. Nhm Steroid: i din ch yu ca nhm lipoid ny l cholesterol v cholesterin
tc l este ca cholesterol v acid bo. Cholesterol c nhiu trong m bo ng vt v vi sinh
vt khc. Trong mu ng vt, hm lng ca n c th t 150-250 mg%. S cng thc
ca cholesterol nh sau:
6.1.1. Tng hp cholesterol: Theo Bloch (1944) cholesterol c tng hp t cc
acetyl-CoA, qu trnh tng hp din ra kh d dng nhiu m:
T acetyl CoA --------------> isopren (CH
3
- C = CH- CH
3
)
n

CH
3
T isopren ----------------> b xng squalen
CH
3
- C = CH- CH
2
- (CH
2
- C= CH- CH
2
)
4
- CH
2
- CH = C- CH
3
)

CH
3
CH
3
CH
3
Sau squalen gp khc to thnh cholesterol.
6.1.2. S chuyn ho ca cholesterol.
Trong qu trnh chuyn ho cholesterol s bin thnh nhiu hot cht sinh hc hoc s
thi theo mt v qua vch rut ga. Mt lng nh c th a ra theo m nhn ca da. T
cholesterol c th chuyn ho cho ra cc sn phm sau:
Cc hormone thuc nhm Steroid nh cc hormonee sinh dc v nhm corticosteroid
(hormone tuyn thng thn).
Cc acid mt gan
Nhm vitamin D nh vitamin D
3
(calcipherol). Cholesterol di da, di tc dng
ca tia t ngoi (=260m) b phn ho to thnh vitamin D
3:
Mt phn cholesterol qua rut gi thi theo phn ra ngoi (di tc ng oxy ho-kh
do vi khun rut gi).
6.2. Nhm phosphateide: y l nhm lipid c phospho lm nhm ghp. Phosphateide
chim v tr quan trng trong qu trnh trao i lipid v protein. Phosphateide xc tin vic
hp thu lipid vch rut, tham gia vo vic vn chuyn lipid v acid bo trong c th. Cht
in hnh ca nhm ny l lecithin
CH
2
O CO R
1

CH O CO R
2
O CH
3

+

CH
2
O P O CH
2
CH
2
N CH
3

OH CH
3

Lecithin gm nhiu cht khc nhau bi cc acid bo (R1, R2
.
).
Phn cholin c th c thay th bi serine to thnh phosphateide serine hoc bng
ethanolamine to thnh phosphateide ethanolamine.
CH
2
OH CH
2
OH CH
2
OH CH
3

CH CH
2
CH N CH
3

COOH NH
2
NH
2
CH
3
Serine Ethanolamine Choline
C th sinh vt c kh nng tng hp phosphateide t cc nguyn liu n gin nh
glycerine, acid bo, acid phosphoric, choline, ethanolamine, serine v.v.
Phosphateide gip cho qu trnh chuyn ho acid bo gan. Nhiu thc nghim cho
thy mt trong cc nguyn nhn ca bnh gan nhim m l v thiu phosphateide m ch yu
l thiu nguyn liu tng hp chng, trc ht l nhm methyl.
Qu trnh phn gii lecithin do lp enzyme lecithinase (phospholipase) y l mt t
hp gm 4 enzyme A,B,C,D. Nhm enzyme ny hot ng lin hon ng thi. Enzyme A
ct acid bo th nht, enyime B ct acid bo th 2, enzyme C ct phosphate, enzyme D ct
choline. Sn phm thu c l cc acid bo, glycerine, acid phosphoric v choline.
7. iu ho qu trnh chuyn ho lipid.
Trao i lipid ng vt chu nh hng chi phi ca hormone v h thn kinh.
7.1. H thn kinh: k c h thn kinh cao cp u c tc dng rt mnh n qu trnh
tch lu m, mt phn l do nhng dy thn kinh i trc tip ti m m, mt phn thng qua
h hormone. Nhng hot ng thn kinh cng thng u lm gim m tch lu trong c th,
ng vt thuc loi hnh thn kinh hng phn thng kh v bo.
7.2. H hormone: Insuline c tc dng xc tin qu trnh tng hp m t nguyn liu
glucid, n thc hin qu trnh phosphoryl ho glucose to nguyn liu cho tng hp m.
Nhm corticosteroid ca tuyn thng thn cng c tc dng thun li cho qu trnh thch lu
m. Nhm hormone sinh dc c tc dng phc tp ti qu trnh ny: hormone sinh dc ci c
tc dng thc y qu trnh tch lu m, ngc li hormone sinh dc c li gy gim tch lu
m.
7.3. Nhng ri lon ca trao i lipid: S chuyn ho lipid c lin quan mt thit n
s chuyn ho glucid. Khi c s ri lon v trao i glucid (v d khi c bnh ng niu) th
s chuyn ho lipid s c tng cng dn n th ceton tng. c th kho mnh, trao i
cht tin hnh bnh thng, hm lng th ceton ca mu rt thp (1-2mg%). Nhng khi c
th suy nhc, hoc khi phi dng lipid lm cht cho nng lng ch yu (nht l khi thiu
Insuline) th th ceton mu c th tng ln rt nhiu (200-300mg%), y l hin tng ceton
huyt. Hu qu ca ceton huyt l ceton niu tc l nc tiu cha nhiu th ceton, lc ny
aceton c hnh thnh v thi theo hi th, theo m hi. Th ceton gy cho c th trng thi
toan huyt v lm ri lon su sc cc qu trnh ho sinh hc ca c th. i vi loi nhai li,
trc ht l b sa, tnh trng ceton-huyt thng gp do chm sc khng ng k thut, khi
khu phn n tha tinh, thiu th.
Khi ni ti ri lon v trao i lipid cng cn ni ti cc trng thi gy ra bi bnh l
ca gan, gan nhim m v.v. Khi c th thiu lipid trong khu phn s dn ti s thiu cc
vitamin ho tan trong lipid nh vitamin A,D,E,K l cc yu t dinh dng rt cn thit. Khi
thiu cc lipid "cn thit" trong khu phn th s lm ngng tr qu trnh phn bo lm cho c
th khng pht trin c.
YU CU CN NM
CHNG VII: LIPID V S CHUYN HO LIPID
Khi nim , Vai tr ca lipid. Mt s c im tiu ho, hp thu, vn chuyn v
d tr lipid ng vt. S phn gii triglycerid. S hnh thnh v chuyn ho th
xeton. S tng hp acid bo v m
Cu 1: Vai tr ca lipit i vi ng vt?
Cu 2: S tiu ho v hp thu lipit?
Cu 3: Vai tr ca gan trong trao i lipit?
Cu 3: Qu trnh -oxy ho axt bo? Tnh hiu qu nng lng khi oxy ho axt bo
palmetic?
Cu 4: S hnh thnh v chuyn ho th xtn trong m bo ng vt?
Cu 5: S tng hp axt bo theo vng son Lynen m bo ng vt?
Cu 6: S tng hp Triglyxerit m bo ng vt?
CHNG VIII
TRAO I PROTEIN
1. ngha ca trao i protein ng vt
Trao i protein gi v tr ch o trong ton b qu trnh trao i vt cht sinh vt,
v bt c hin tng sng no cng u gn lin trc tip vi s trao i protein. S sinh
trng, pht dc ca ng vt c ni dung c bn l trao i protein. S di truyn, bin d
cng gn trc tip hay gin tip n trao i protein. Cho nn hiu c hin tng sng
ca sinh vt tin ti chi phi c hin tng ny theo hng c li cho con ngi cn phi
hiu su sc v trao i protein.
Protein quan trong i vi ng vt xt theo 2 mt:
ngha v to hnh: Protein l nn tng, l loi cht ch yu cu to nn mi m bo
sinh dch, l cc cht c hot tnh sinh hc quan trng nh enzyme, cc khng th, cc
hormone...; cc m bo nh c, xng, mu, no, tu... Protein trong c th ng vt lun
lun trng thi ng, trng thi trao i, lun lun c i mi tc l trng thi ng
ho v d ho, y l c s ca mi s pht trin ng vt. Bng phng php nguyn t
nh du, ngi ta bit c thi gian tn ti ca hng cu l 2-4 thng, ca enzyme
amylase l 2 gi, ca b xng l 5-10 nm. Chnh v vy hng ngy c th lun lun i hi
mt ngun acid amin theo vi thc n vo b p li nhng b phn gi ci b thi b
trong qu trnh d ho.
ngha v nng lng: trong qu trnh d ho mt phn protein cng b oxy ho cho
nng lng, 1g protein khi oxy ho hon ton cho ra 4,1 Kcal
2. c im ca trao i protein ng vt
Trao i protein c mt s c im khc vi cc trao i cht khc l:
2.1. Vn cht lng ca protein: ng vt mun c qu trnh sinh trng v pht
dc bnh thng th phi c y protein trong khu phn. y protein phi hiu trc
ht l v mt cht lng c ngha l thnh phn cc acid amin trong protein. nhiu ng vt
nht l ng vt nng nghip v ngi kh nng t tng hp mt s acid amin b hn ch,
nn nhng acid amin ny bt buc phi c cung cp theo khu phn. i vi a s ng vt
nhng acid amin ny l: Tre, Met, Val, Phe, His, Try, Lyz, Leu, Ileu. S acid amin khng thay
th ny cn ph thuc vo ging, la tui, v d Arg v Gly li rt thiu i vi g con. i
vi loi nhai li nh tru, b, d, cu th nhu cu acid amin t thc n khng cng thng lm
v c h vi sinh vt cng sinh ng tiu ho tng hp c tt c cc loi acid amin
Cht lng y cn c hiu theo ngha v mt tiu ho: d hay kh tiu ho, v d
protein trong sa khc vi trong gn, sa s tiu ho hu nh hon ton, cn gn l rt t.
2.2. Qu trnh hp thu: Cc acid amin hp thu qua vch rut theo mt tng quan s
lng nht nh. V d theo Wiliam t l % thch hp ca cc acid amin khng thay th i
vi ln con cho qu trnh hp thu (tnh % theo lyzin) nh sau:
Lyz: 100; Try: 9; Met v Cys: 34; His: 33; Val: 12;
Tre: 45; Leu: 85; Tyr v Phe: 78; Ileu: 47.
T l tng quan ny khi b mt cn bng th c hai kh nng:
C th c th iu lng acid amin thiu vo rut b tng quan v s lng cho
vic hp thu c ht acid amin. Nhng acid amin ngi ta gi l ngun ni t ni sinh.
Ngun ni t ni sinh ny bao gm nhng sn phm ca c th nh cc enzyme ca ng tiu
ho (aminase...), cc bch cu...
Nu c th khng b p c th nhng acid amin "tha" (tha thiu) khng c hp
thu s b thi ra ngoi v kh nng b p ca c th cng c hn.
y chnh l c s ca vic b xung thc n trong xy dng khu phn n cho gia sc,
chnh l s b xung cc acid amin thiu trong thc n, bng cch nng cao c cht
lng thc n, bin thc n r tin thnh thc n c gi tr.
2.3. C th khng d tr c protein: Mi c th ch s dng protein ti mt mc
nht nh, nu tha n s b thi ra ngoi di dng ure, uric... hoc b bin i sang dng
ng, lipid d tr. Qu trnh tch lu protein ch c ng vt non, ng vt mi m dy.
Ngi ta a ra khi nim v cn bng nit nh sau: Cn bng nit l xt s lng nit a
vo c th (theo thc n, nc ung...) v s lng nit bi tit ra ngoi c th theo phn,
nc tiu, m hi trong mt khong thi gian nht nh.
Trong qu trnh sng ca ng vt c ba trng thi:
Cn bng dng: N a vo c th > N a ra khi c th. Hin tng ny c
ng vt non, ng vt mi m dy, ng vt c cha.
Cn bng: N a vo c th = N a ra khi c th. Hin tng ny c ng vt
trng thnh (ngi 24-45 tui).
Cn bng m: N a vo c th < N a ra khi c th. Hin tng ny c ng
vt gi, suy thoi, ang m.
Hnh 8.1. th v qu trnh tch lu N mt c th ng vt trong qu trnh sng
ng vt trng thnh, hng ngy i hi mt lng protein ti thiu bo m
thay th cc m bo, cc hot cht nh enzyme, hormone, khng th... gi ci. Lng
protein ti thiu ngi ta gi l protein minimum. S lng ny khc nhau cc ng vt,
nhng nhn chung vo khong 1g/1kg khi lng/1ngy. L do sinh vt khng d tr protein
l v mi sinh vt trong qu trnh tin ho trong mi trng sinh thi c kch thc nht
nh, v protein l nn tng ca cu to m bo, t bo nn protein khng th tch lu v tn,
n s lm ph v kch thc c c nh ca sinh vt.
3. Tiu ho v hp thu protein
Protein ni chung c a vo c th thng qua con ng tiu ho. Trong ng tiu
ho nhng protein no c tnh d ho tan trong nc th kh nng tiu ho cao nh globulin,
albumin ca trng, sa, cn nhng protein no km hoc khng ho tan trong nc th tiu
ho ho kh khn hoc khng tiu ho c nh protein ca gn, dy chng...
* xoang ming: khng c enzyme tiu ho protein, ming protein ch chu tc ng
c hc (tuy nhin ming c peptidase ca VSV c tr trong xoang ming, chng phn hu
protein thnh nhng cht c mi hi).
* d dy: y l khu vc tiu ho protein mnh nht, v y c iu kin ti u
tiu ho protein l:
pH =1,5-2,5. Mi trng acid ny l do t bo ph tit HCl, pH ny c tc dng l
mi trng st trng tt, hu ht cc tp trng b tiu dit trong mi trng ny; lm chng
n protein lm cho cc lin kt peptide d b enzyme tc ng, mt s lin kt peptide b thu
phn ngay mi trng acid ny, nn nhng ng vt v l do no m nh hng ti
pH ny th s nh hng ti s tiu ho protein, c bit ng vt non ang b sa m,
ngi ta phi cho ung thm dch v nhn to. HCl cn c tc dng hot ho enzyme
pepsinogen.
Enzyme pepsin: do t bo chnh thn v tit ra, khi mi tit ra dng pepsinogen
cha c hot tnh, c khi lng phn t 42.000 dalton, n b che ph bi mt peptide c khi
lng phn t 7.000 dalton (hnh 8.2). Di tc dng ca H
+
on peptide ny b ct i, gii
phng trung tm hot ng, tr thnh pepsin hot ng. Khi hot ng n li hot ho
pepsinogen, qu trnh ny mnh hn do H
+
. Pepsin c hot lc phn gii protein cao nht
trong cc enzyme tiu ho protein (2gam/1 gi phn gii c 50kg lng trng trng).
Hnh 8.2. M hnh v pepsinogen
Pepsin l enzyme peptidase ni, n ct lin kt peptide gia phn t to thnh cc
on peptide v ct lin kt peptide c hiu, lin kt peptide c cc acid amin mch vng.
Tuy nhin nu thi gian th tt c cc lin kt peptide u b ct.
Chimozin (Rennin): l enzyme c ng vt non trong giai on b sa. Tc dng
chnh ca enzyme ny l lm ng vn caseinogen thnh caseinoat Ca
++
lu li d dy
cho pepsin tc dng.
D dy cng l protein nhng khng b pepsin phn gii, l do nim mc d dy
c ph bi mt lp polisacarid (mucoproteid), mt khc pH ca m d dy l 7,3 khng
ph hp vi hot ng ca pepsin, ngoi ra n cn b chi phi bi h thn kinh. Nhng hot
ng thn kinh cng thng v ko di thng dn n au d dy.
* rut non: Mi trng y l kim pH=8-9. HCl t d dy a xung b trung ho
bi cc bicarbonat do dch tu tit ra:
NaHCO
3
+ H
+
----- > Na
+
+ H
2
CO
3
Cc enzyme tiu ho protein y do tuyn tu tit ra l ch yu, mt phn do tuyn
rut tit ra.
Tuyn tu tit ra cc enzyme sau:
Trypsinogen: Trypsinogen c khi lng 23.000 dalton cha c hot tnh, di tc
dng ca enterokinase do tuyn rut tit ra n c hot ho thnh trypsin c hot tnh.
Hnh 8.3. Cu trc phn t trypsinogen
Trong trypsinogen His b dy ni ph ko lch khi v tr trung tm hot ng xa Ser
(hnh 7.3). Di tc dng ca Entero kinase ct lin kt Lyz-Val v cc lin kt ph lm cho
His tr v trung tm hot ng. Khi hot ng trypsin li c tc dng hot ho trypsinogen.
Trypsin ct lin kt gia ca chui peptide v lin kt c cha cc acid amin kim tnh, tuy
nhin nu c thi gian th n cng ct ht tt c cc lin kt cn li.
Chimotrypsinogen: khi mi tit ra trng thi cha hot ng, phn t gm 246 acid
amin, c 5 cu disunfid (hnh 8.4). Khi lng phn t 21.000 dalton, n c hot ho bi
Trypsin. Qu trnh hot ho nh sau:
Hnh 8.4. Cu trc ca chimotrypsin
Trypsin ct lin kt peptide 14-15, chimotrypsinogen chuyn thnh chimotrypsin c
hot lc nhng cu trc khng bn v hot lc yu.
Trypsin ct lin kt peptide 114-115 (Ser v Arg), chimotrypsinogen chuyn thnh
chimotrypsin khng c hot lc.
Trypsin ct lin kt peptide 148-149 (Tre v Asp) chimotrypsinogen to thnh 3 on
peptide ni vi nhau bng 5 lin kt disunfid chuyn thnh chimotrypsin c hot lc cao v
bn vng trong mi trng base v acid. Chimotrypsin c tc dng ct lin kt peptide to bi
acid amin mch vng, Leu, ILeu v Met.
Carboxyl peptidase: khi mi tit dng pro carboxyl peptidase cha c hot tnh, n
c hot ho bi trypsin v chimotrysin to thnh 2 dng hot ng A v B. Chng c tc
dng ct lin kt peptide u c nhm carboxyl (-COOH). Dng A ct lin kt peptide pha
COOH to bi acid amin trung tnh, dng B ct lin kt peptide pha COOH to bi acid
amin kim tnh. c im ca enzyme ny l hot ng phi c Zn
++
tham gia, Zn
++
l cu ni
gia enzyme vi c cht (hnh 8.5).
Lin kt peptide c ct
R C
O
N
H
C
H
R'
CH
2
COO-
Zn2+
Enzyme carboxyl peptidase
Hnh 8.5. Zn
2+
l cu ni gia enzyme vi c cht
Vch rut tit ra cc enzyme:
Enterokinase c tc dng hot ho trypsinogen do tuyn tu tit ra.
Amin peptidase c tc dng ct lin kt peptide t pha cc acid amin d nhm NH
2
.
Di tc dng ca cc enzyme k trn protein c phn gii thnh cc acid amin.
i vi nhm nucleoproteid do enzyme nuclease phn gii, bao gm: Ribonuclease
phn gii RNA v desoxiribose phn gii DNA thnh nucleotide. Nucleotidase phn gii
nucleotide thnh cc base, ng v phot phat.
S tiu ho protein ph thuc vo cht lng protein v trng thi ng tiu ho.
Trong iu kin bnh thng, protein ca sa t l tiu ho t 95-97%, tht nc 80-85%, gn
dy chng rt t.
Phn ln cc acid amin c hp thu qua vch rut kh d dng, phn cn li khng
c hp thu cng vi protein khng c tiu ho s chuyn xung rut gi, y n b
phn hu do VSV ca rut gi. S hp thu cc acid amin qua vch rut theo nhiu c ch, ch
yu l c ch tch cc i hi nng lng ca ATP. Cch th hai l di dng -Glutamin-
acid amin.
Trong iu kin bnh thng peptide, protein khng c hp thu qua vch rut, nguyn
nhn l do ngha sinh hc ca n. Bnh thng c th c cc phn ng min dch, l phn
ng chng li cc d vt l protein. V protein l cht mang s sng, n c th l virut, vi
khun nn c th phi cnh gic vi nhng d vt ny v trong qu trnh tin ho sinh ra
cc khng th min dch, l nhng protein c kh nng chng li cc d vt trn (cc khng
nguyn), y l phn ng t v ca c th. Khi protein phn gii thnh cc acid amin n
khng cn tnh c trng sinh hc na mi c hp thu. C hai trng hp ngoi l:
Nu ung tht nhiu lng trng trng th trong nc tiu phn tch thy c cht ny, s
hp thu ny l b ng, c th b trng c, n c o thi ra ngoi qua nc tiu.
Trng hp gia sc s sinh trong tun l u n hp thu khng th sa u ca m
(hp thu ch ng), y l cch truyn khng th ca m cho con. Trong sa u ca m c
rt nhiu khng th, c bit l nhm IgA l khng th gy min dch cc b. Trong sa u
cn c cht c ch trypsin nn khng th khng b phn gii. Vic hp thu khng th theo con
ng m bo. Gia sc s sinh rt cn b sa u, nu khng t l t vong s cao. Sau tun l
u th kh nng ny s b ht.
Acid amin c hp thu qua vch rut vo tnh mch, qua tnh mch ca v gan ri
theo h tun hon n cc m bo hoc gan s dng tng hp nn protein ca c th.
4. S chuyn ho trung gian ca acid amin
Acid amin sau khi c hp thu c a vo mu, mt phn s c gi gan, mt
phn s c chuyn ti cc c quan, cc m bo khc. Lng acid amin cng vi s acid
amin hnh thnh trong qu trnh phn gii i mi ca m bo, hng ngy hp thnh lng
acid amin chung c a vo vng chuyn ho. Lng ny nhiu hay t l tu loi sinh vt,
tu trng thi trao i cht ca c th. Cch chuyn ho ca acid amin c th theo hai hng:
Hng th nht l dng vo qu trnh sinh tng hp thnh peptide, protein, trong
thng xuyn nht l sinh tng hp enzyme, khng th v hormone.
Hng th hai l chuyn ho phn gii, thng qua con ng ny acid amin b mt nit
bin thnh cc cetoacid v c chuyn ho, oxy ho n dng CO
2
v H
2
O, ng thi gii
phng ra nng lng dng cho cc nhu cu sng ca c th. Ni t c bi tit y ch yu
di dng mui amon, ure v acid uric.
4.1. S phn gii acid amin
Trong c th ng vt acid amin c th b phn gii thng qua 3 phn ng in hnh l
phn ng kh amin, phn ng chuyn amin v phn ng kh carboxyl. Ngun acid amin i
vo con ng phn gii ch yu l t cc acid amin ni sinh (t cc hormone, enzyme, cc
khng th hoc t cc t bo gi ci b phn gii do h thng catepsin nm trong lyzoxom),
cn t thc n l rt t.
4.1.1. Phn ng kh amin
Phn ng ny c tin hnh mnh gan, vch rut. Trong phn ng ny acid amin b
phn gii thnh cc cetoacid v amiac. Trong gii sinh vt c nhiu cch thc hin phn ng
kh amin, cn trong m bo ng vt th con ng kh amin theo con ng oxy ho di
tc dng ca nhm enzyme oxydase. i vi acid amin hng D th c coenzyme l FAD
+
, i
vi acid amin hng L th coenzyme l FMN
+
.
Phn ng din ra nh sau:
FMNH
2
+ O
2
------ > H
2
O
2
(peroxyt hydrogen) + FMN
Catalase
H
2
O
2
(peroxyt hydrogen) ---------------- > H
2
O + O
2
FMNH
2
khng a cp H
+
vo chui h hp, n a cho oxy nn gi l enzyme
oxydase.
H
2
O
2
l cht c i vi c th nn n c catalase chuyn ho thnh nc v oxy
phn t. Chiu ca phn ng ny khng c chiu nghch, y l con ng phn gii trit
acid amin. Enzyme oxydase c tnh c hiu khng cao, mt enzyme c th kh c hng
chc acid amin
S kh amin thun nghch ca acid glutamic:
Acid glutamic c vai tr c bit quan trng trong trao i protein, enzyme thc hin
phn ng kh amin ca n l glutamat dehydrogenase c nhm ghp l NAD
+
hoc NADP
+
.
y l enzyme b tr trong ty lp th, c hot lc cao gan v tuyn thng thn. Phn ng
nh sau:
ngha ca phn ng: l phn ng c tnh thun nghch cao, thng qua phn ng
nghch l con ng amin ho cc hp cht hu c, bin NH
3
l cht c i vi c th thnh
sn phm c gi tr (phn ng l ca ng a cht v c NH
3
vo th gii hu c). Phn
ng theo chiu nghch ch yu xy ra th gii thc vt v VSV.
Phn ng theo chiu nghch l c ch gii quyt lng NH
3
khi c th b trng c
kim.
Vai tr ca acid glutamic trong trao i acid amin l rt ln, acid glutamic l cht khi
thu ca cc acid amin, n ng vai tr cung cp nhm amin ch yu cho qu trnh tng hp
cc acid amin khc thng qua phn ng chuyn amin.
i vi mt s acid amin c bit nh SER, CYS, TRE, HIS, TRY, ASP phn ng kh
amin ca chng i theo con ng kh nc. Enzyme thc hin phn ng ny l
dehydrogenase c nhm ghp l phospho piridoxal l dn xut ca VTM B
6
.
CH
2
OH
N
CH
2
HO
H
3
C
OH
VTMB6
CH
2
OH
N
CH
2
HO
H
3
C
O P
O
E
OH
O
Photphopyridoxal
V d phn ng kh amin ca serin:
4.1.2. Phn ng chuyn amin
Trong chuyn ho acid amin m bo ng vt cng nh sinh vt khc, phn ng
chuyn amin gi mt vai tr quan trng hng u. Thng qua phn ng ny th gii thc vt
v vi sinh vt c kh nng to nn cc acid amin mi. Kh nng ny cng c m bo ng
vt, tuy nhin y c hn ch hn. Phn ng ny din ra mnh gan, vch rut. Phn ng
c thc hin bi h thng enzyme c bit gi l transaminase (cn gi l amin ferase).
y l nhm enzyme phc tp c kch thc phn t kh ln (255acid amin 25.500 dalton),
c nhm ghp cng l phosphopiridoxal. S phn ng nh sau:
Acid amin Cetoacid Cetoacid mi Acid amin mi
y l phn ng thun nghch, trong c th ng vt cht cho amin thng l nhng
acid amin cn kh amin, cht nhn thng l - cetoglutarat, trong trng hp cn tng hp
cc acid amin th cht cho amin thng l acid glutamic.
C ch ca phn ng thc hin qua cht trung gian l kim shiff (hnh 8.6).
Trong c th ng vt c hai cp phn ng chuyn amin thc hin kh mnh, l:
Cp thc hin bi enzyme Glutamat - Oxaloaxetat - Transaminase (GOT)
Cp thc hin bi enzyme Glutamat - Pyruvat - Transaminase (GPT)
Hnh 8.6. C ch phn ng chuyn amin
Hai cp enzyme GOT v GPT hot ng mnh gan, c, tim v nhiu m bo khc.
Trong chn nui vic nh lng hot lc cc enzyme ny c ngha quan trng, thng qua
hot lc ca chng, ngi ta c th bit c cng chuyn ho acid amin, t gin tip
bit c cng trao i protein cng nh trao i cht ni chung ca con vt, ng thi
c th xt on v phm cht con ging, kh nng hp thu thc n, kh nng sinh trng v
pht trin... Trong nhiu trng hp ngi ta thy c mi lin quan cht ch gia tnh di
truyn vi cc ch s enzyme ny. Trong th y vic nh lng hai enzyme ny trong mu c
ngha trong chn on bnh v tim v gan. Hot lc hai enzyme ny trong mu l hot lc
ca enzyme do t bo b v, c hai kh nng b v, c th m bo pht trin mnh th t bo
c b v nhiu nh trong trng hp ung th, hoc c kh nng b v do bnh l nh trng
hp b hoi t. V vy khi xt nghim thy hot lc GOT tng cao th nghi c bnh v tim
(enzyme ny c nhiu tim), nu GPT tng th nghi c bnh v gan (enzyme ny c nhiu
gan).
4.1.3. Phn ng kh carboxyl
Phn ng ny thc hin bi h thng enzyme decarboxylase cng c nhm ghp l
phospho piridoxal, enzyme ny c tnh c hiu cho tng loi acid amin. S phn ng nh
sau:
COOH
C - NH
2
R
+
C - NH
2
R
CO2 Decacboxylase
Acid amin Amin hu c
Qu trnh kh carboxyl din ra tt c cc m bo vi cng bin i khc nhau.
Cc acid amin sau khi bin thnh cc amin tng ng, tr vi trng hp cn ni chung u
c c hot tnh sinh hc cao, mt s cht cn c hot lc dc hc v c vai tr quan trng
i vi hot ng sng cu c th. V d:
S bin i ca Tyrosine:
Tyrosine Tyranin Nor adrenalin Adrenalin
Adrenalin v Nor adrenalin l hormone ca tuyn thng thn.
S bin i ca Tryptophan:
Serotonin v melatonin l hormone ca tuyn tng iu khin v tnh dc, l "con mt
th ba" gy sinh theo ma, n nhn cm v nh sng ngy ngn, ngy di.
S bin i ca Histidin:
Histamin l cht kch thch mnh ln t bo thn kinh gy cm gic au. cc m lin
kt c cc t bo ph i c cc ti cha histidin. Khi b vim, b vp ng, cc ti ny v gii
phng histidin, histidin b enzyme decarboxylase tc ng to ra histamin gy nn au n.
Nu lng hidamin qu ln gy nn hin tng chong ngt. Histamin cn gy nn hin
tng d ng (nc ong v mt s v cy c cc cht c tc dng hot ho enzyme
decarboxylase ca histidin to nn histamin nn gy au, d ng). Vi lng nh histamin c
dc tnh lm tng co bp c trn, gin mch qun v tng tnh thm ca thnh mch qun,
gy gim huyt p, trong sn khoa c th dng n tr lc co bp c t cung.
S bin i ca Acid glutamic:
Decarboxylase
Acid glutamic -------------------- > -amin butylic acid (GABA).
GABA l cht ng vai tr quan trng trong iu ho hot ng thn kinh trung ng.
N c ch s dn truyn xinap. V l do no m enzyme decarboxylase ca acid
glutamic khng hoc thiu acid glutamic, lm lng GABA thiu, khng gy c ch c
s gy nn lon thn kinh, nh l mt ng, ngc li nu GABA sinh ra qu nhiu thn kinh
trng thi c ch.
S bin i ca Lyzin v Ornitin:
- CO
2
Lyzin: CH
2
-(CH
2
)
3
-CH-COOH ------------> CH
2
-(CH
2
)
3
-CH
2
-NH
2

NH
2
NH
2
NH
2

Lyzin Cadaverin
- CO
2
Ornitin: CH
2
- (CH
2
)
2
- CH- COOH ------------> CH
2
- (CH
2
)
2
- CH
2
- NH
2

NH
2
NH
2
NH
2
Ornitin Putrescin
Cadaverin v Putrescin l nhng cht ht sc c i vi c th (cadaverus l xc cht,
putrus l s thi ra) ch cn 1mg putrescin tim vo mu s lm cht mt con nga 500kg
ngay tc khc. Chnh v c tnh ca n nn trong c th khng c 2 loi enzyme kh
carboxyl ca 2 loi acid amin ny, n thng do vi khun phn hu.
Nhn chung cc amin hu c u c hot tnh sinh hc mc khc nhau. Nu nng
thch hp th n l cc dc liu qu.
Cc amin hu c sau khi ht tc dng s c thoi ho theo con ng kh amin v
oxy ho nh enzyme mono amin oxydase to NH
4
+ v aldehydeyd. Cc aldehydeyd tip
tc oxy ho to thnh acid cacboxylic v tip tc oxy ho thnh CO
2
v H
2
O.
5. S thi ra ca protein rut gi do vi khun
Tu theo khu phn, tu loi thc n m lng protein b tha n rut gi t nhiu khc
nhau. T l ny cn ph thuc vo hot ng ca enzyme tiu ho, s hp thu v bnh ng
rut... Trong rut gi s lng vi khun rt ln (1g phn trung bnh c 17 t vi khun), trong
c nhiu chng loi khc nhau, nhiu nht l E.coli. Ngi ta chia vi khun rut gi lm 2
nhm:
Nhm vi khun c ch: gip cho c th sn sinh mt lot cc cht cn thit, nht l
vitamin nhm K, E... i vi tru b, nga, th, ngng cn ng vai tr phn gii cellulose
thnh acid bo bay hi v vitamin nhm B cho c th. Qa trnh ny din ra manh trng.
Nhm vi khun c hi: trong iu kin bnh thng nhm vi khun ny trng thi b
c ch nn n khng gy hi. Khi b ri lon thc n n hot ng mnh v gy hi. i vi
thc n protein, tt c cc hot ng ca vi khun u gy hi, v n sn sinh ra cc cht c
nh cadaverin, putrescin, indol, scatol, phenol... Nhng sn phm ny thm qua vch rut vo
mu gy c cho c th. C th i ph bng cch trung ho c tnh ca n gan. Gan l c
quan kh c cc cht ny. y cc cht ny b oxy ho sau c ghp vi H
2
SO
4
hoc
vi acid glucoronic to thnh cc hp cht kp khng c v c thi ra ngoi qua nc tiu
(hnh 8.7). Cc hp cht kp nh lng qua nc tiu c tn l indican, hm lng indican
nh gi kh nng tiu ho hp thu protein ca c th.
N
H
N
H
CH
3
O
N
H
CH
3
N
H
OH
N
H
O HSO
3
COOH
Indol
Scatol
Indoxyl
N
H
CH
3
OH
Scatoxyl
Indolsulfuric
Scatoxylglucoronic
Hnh 8.7. S chuyn ho ca Indol
6. S bi tit cc cht cn b cha nit
Trong qu trnh phn gii acid amin cng nh mt s sn phm cha nit khc nh cc
base purin, pirimidin... amiac thng xuyn c hnh thnh, l nhng cht c, do c
th phi thng xuyn gii quyt s ng amiac. Cch bi tit cht cn b ny khc nhau
cc sinh vt. loi sinh vt c cu to th s nh amid v sng trong mi trng nc th
amiac bi tit trc tip ra t bo di dng ion amoni (NH
4
+
). nhng sinh vt c cu to
phc tp v mi trng nc bt u b hn ch nh ng vt cao ng sng trn cn th NH
3
trc khi bi tit phn ln c chuyn sang dng hp cht ure, gi l ng vt bi tit ure.
Mt s ng vt trong qu trnh pht trin c tri qua giai on pht trin trong trng
l mi trng ht sc hn ch v nc, hn na hnh thc di chuyn li l bay th sn phm
bi tit cha nit ch yu l acid uric (v uric km ho tan trong nc).

Ure Acid uric
ng vt c v sn phm bi tit cha nit gm nhiu dng, trong ch yu l ure
(chim 90% sn phm cha nit trong nc tiu), bn cnh ure cn c cc mui amon nh
sunphat amon, oxalat amon, phosphate amon, nhng mui ny hnh thnh ngay t bo thn,
mt phn acid uric v sn phm phn gii ca n l alantoin.
C
NH
2
NH
2
O
N
N
N
N
H
OH
OH
HO
6.1. S vn chuyn amiac trong c th.
Tt c cc m bo, cc t bo u c hnh thnh nn amiac. T m bo n c ch ti
gan v thn di dng glutamin. Qu trnh hnh thnh glutamin c thc hin bi enzyme
glutamin syntetase:
- H
2
O O
COOH- CH- (CH
2
)
2
- COOH + NH
3
--------- > COOH- CH- (CH
2
)
2
- C
ATP, Mg
++
NH
2
NH
2
NH
2

Acid glutamic Glutamin
Glutamin chim 1/5 tng s nit phi protein trong mu, dng ny chng c ch ti
gan, thn tng hp nn cc sn phm bi tit.
Amiac l cht c i vi t bo, c bit l t bo thn kinh v khi ng n lm thay
i pH ca mi trng bo tng, gy trng thi kim, mt khc nu lng amiac qu ln,
lng -cetoglutarat b huy ng qu nhiu lm tc chu trnh Krebs lm t bo thiu nng
lng.
Nhiu nghin cu chng t hiu ng c ln nht ca NH
3
trong no bao gm s
thay i pH ca t bo v lm cn kit c cht ca chu trnh Krebs. Dng mang proton ca
amonium (NH
4
+
) c tnh acid yu v dng khng mang proton c tnh base mnh. Khi chuyn
ho to nhiu NH
4
+
s gy nn Kim ho dch t bo.
gan v thn glutamin c s dng vo cc mc ch sau:
Chuyn amin cho cc cetoacid to ra cc acid amin mi.
Chuyn amin to cc base purin, pirimidin.
Gii phng NH
3
tng hp ure, qu trnh ny c thc hin gan.
Gii phng NH
3
to cc mui amon v bi tit. Qu trnh ny thc hin thn. y
Na
+
c gii phng ra khi mui ca n v c t bo thn hp thu tr li nhng ch cho
NH
4
+

NH
4
+
+ NaHCO
3
------ > Na
+
+ NH
4
HCO
3

6.2. S tng hp v bi tit ure (chu trnh Ornitin)
Qu trnh tng hp ure c thc hin ty lp th ca t bo gan ca ng vt c v,
ng vt cn. Qu trnh ny c thc hin bi mt h thng enzyme hot ng lin hon
vi nhau gi l chu trnh ornitin bao gm cc phn ng sau:
1. To carbanyl phosphate do enzyme carbanyl phosphate syntetase
C = O
NH
2
O - P = O
CO2 + NH3
2AIP
2ADP+Pi
Carbanyl p.syntetase
OH
OH
Carbanyl photphat
2. To xidrulin do enzyme ornitin carrbanyl phosphate transferase
C = O
NH
2
O - P = O
OH
OH
Carbanyl photphat
H
2
N CH COOH
(CH
2
)
3
NH
2
C = O
NH
2
NH
(CH2)3
CH - NH
2
COOH
+
Ornitin
Xitrulin
-H3PO4
3. Ghp thm NH
3
t acid aspartic do enzyme argino succinat syntetase
4. Phn ng to arginin do enzyme arginosuccidase
5. To ure do enzyme arginase ( enzyme ny ch c t bo gan ng vt bi tit ure)
Ure hnh thnh gan c a ra mu v c bi tit ch yu qua nc tiu, do
trong mu bao gi cng c mt lng ure ang di chuyn nht nh, lng ny thay i cc
loi ng vt, nhn chung chng chim khong 1/2 nhm nit phi protein, t l ny ng vt
n tht cao hn ng vt n c. Ure chim gn 90% lng nit ca nc tiu. Mt phn ure
c bi tit qua m hi, qua nc bt. ngi v nga ure bi tit qua m hi kh ln.
ng vt nhai li ure nc bt c ngha ln v ti d c n c phn gii thnh amiac,
amiac li c VSV d c chuyn ho thnh acid amin v thnh protein ca bn thn t bo
VSV. VSV li l ngun protein cho loi nhai li, y l chu trnh chuyn ho khp kn ca
nit loi nhai li, nh vy tit kim c ngun nit.
6.3. S bi tit acid uric
Acid uric l dng bi tit cht cn b cha
nit ch yu ca gia cm, cc loi chim, b st,
nhuyn th. Acid uric cn c th l dn xut
trc tip ca qu trnh chuyn ho base purin
Ngun gc nit trong acid uric u xut
pht t NH
3
do s chuyn v kh amin (hnh
8.8).
Hnh 8.8. Ngun gc N trong acid uric
S chuyn ho t adenin:
S chuyn ho t guanin:
Acid uric l mt cht km ho tan trong nc nn khi bi tit n thng trng thi
huyn dch, cht trng trong phn gia cm l dng mui ca acid uric. Acid uric cng c
nc tiu ca ng vt c v, nhng y n ch l sn phm ht sc ph ca s chuyn ho
base purin.
Tr loi linh trng cn tt c cc loi ng vt c v khc cn bi tit nit di dng
alantoin l s chuyn ho ca acid uric di tc dng ca enzyme uriase. Phn ng nh sau:
Alantoin cn c th b v ra thnh 2 phn t ure v acid oxalic ( COOH COOH).
Khi b ri lon trao i aciduric, aciduric b ng trong mu n s lin kt li thnh
ht ng li cc khp sn gy nn bnh gut. Acid uric thng ng khp ngn chn, ngn
tay, di tai, b thn, nu b thn th c th gy si thn.
loi nhn s bi tit nit l guanin, c m l acid trimetyl aminoacid:
N
CH
3
H
3
C
CH
3
O
7. Chuyn ho ca cc protein phc tp.
7.1. S chuyn ho ca hemoglobine.
Trong phn ny chng ta ch xem xt s thoi ho hemoglobine v s hnh thnh sc t mt.
Cc kha cnh ny rt hay c cp trong thc t.
i sng trung bnh ca hng cu cc sinh vt l khc nhau: ngi l 126 ngy, th,
mo l 45-68 ngy, ln 62-71 ngy, ch l 107 ngy v g l 28 ngy. Hng cu b phn
gii do gi hoc do nh hng ca ngoi cnh (tc ng c hc, vp, ng...). Ni phn hu
hng cu l gan v lch ( khi b st rt, lch lm vic qu sc nn b sng, gy bng bng, da
b vng do hng cu v nhiu, sc t mt trn ra nim mc gy hong n).
gan v lch t bo thc bo lm v mng hng cu, hemoglobine gii phng b ct
mt dy ni metyl (= CH -) to thnh verdoglobin. Nu hng cu b v mu th
verdoglobine s kt hp vi haptogobin (yu t vn chuyn nm trong tiu phn -globulin)
vn chuyn ti gan hoc lch. gan v lch haptoglobine c tch ra.
Qu trnh gan: gan globin c tch ra khi verdoglobine v vo con ng
chuyn ho ca protein. Fe
+2
tch ra c lin kt vi globulin to thnh feratin v c a
ra mu mang tn l transferin ri chuyn ti tu xng tng hp nn hng cu mi.
Vng pocfirin v, di tc dng ca enzyme oxygenase b m C gii phng CO,
tch Fe
+2
v nc vi s tham gia ca CO
2
, NADPH
2
to thnh biliverdin c mu xanh ve,
y l yu t to nn sc t mt. Cht ny chim 15-20% khi lng kh ca mt ngi.
Biliverdin tc dng vi NH
2
to thnh bilirubin. Hai cht biliverin v bilirubin khng
ho tan trong nc m ho tan trong lipid, l cht c i vi c th, n c ch thn kinh m
tu v kch thch cc mt thn kinh. V l do no m cc cht ny b ng gan, s trn
vo mu lm cc nim mc nhim mu vng gy chng hong n. Ti gan chng c gan
kh c bng cch gn vo acid glucoronic bin thnh phc hp bilirubin-glucoronic
khng c, d ho tan trong nc bi tit.
Phc hp bilirubin-glucoronic c a ra rut theo ng mt ti rut gi, y chng
c vi khun rut gi phn gii thng qua phn ng oxy ho - kh to thnh mesobilinogen
khng mu. Mesobilinogen chuyn ho theo hai con ng:
Mt phn to thnh stercobilinogen mu vng theo phn ra ngoi, gp khng kh chng
b oxy ho thnh stercobilin c mu thm (hnh 8.9).
Mt phn thm qua vch rut vo mu c a ti thn, y chng chuyn thnh
urobilin c mu vng theo nc tiu ra ngoi.
Qu trnh lch: lch qu trnh c chuyn n dng biliverdine th c chuyn
v gan kh c.
7.2. Ri lon chuyn ho Hemoglobine.
Bnh thng, hm lng bilirubin huyt thanh khong di 1mg/100ml (0,2 0,8mg)
ch yu di dng t do, cn dng lin hp ch dng vt.
Trong cc trng hp bnh l, bilirubin huyt thanh c th ln ti trn 20mg%. Nu
bilirubin lin hp tng th n s khuch tn qua thnh lin kt ra cc t chc c bit l da v
nim mc gy vng da v bilirubin lin hp tan trong nc. Nu tng bilirubin t do lm vt
qu kh nng kt hp ca albumin huyt thanh, phn bilirubin cn li s tch khi thnh lin
kt v khuch tn vo cc m v cng v th gy s lng ng bilirubin cc m ch yu l
da v nim mc gy vng da. Nh vy vng da c th do bilirubin t do, cng c th do
bilirubin lin hp v vng da c xp theo 3 nhm chnh sau:
Vng da do nguyn nhn trc gan: Mi trng hp tan huyt hay hng cu b ph hu
hng lot u lm tng thoi ho hemoglobine v dn n tng bilirubin t do. Khi bilirubin
t do tng m gan khng lin hp ht th dn n kt qu l bilirubin ton phn tng nhng
tng ch yu l bilirubin t do. Trong trng hp ny nc tiu khng c bilirubin t do (v
khng tan trong nc). S to thnh mt lng ln urobilinogen v Stercobilinogen trong
mu dn n tng urobilinogen trong nc tiu v tng Stercobilinogen trong phn.
Vng da do nguyn nhn ti gan: trong trng hp vim gan do virus, tn thng t bo
nhu m gan lm chc nng gan b gim. Trong c chc nng lin hp vi bilirubin lm cho
bilirubin t do trong mu tng. ng thi khi vim gan cc nhu m gan b ph n v gy chn
p cc vi qun mt gy tc mt lm cho bilirubin lin hp khng xung mt v rut, tro vo
mu gy tng c bilirubin lin hp. Nh vy, khi b vim gan th bilirubin ton phn ca huyt
thanh tng cao c dng t do ln dng lin hp. Nc tiu trong trng hp ny c bilirubin
lin hp hay sc t mt, urobilinogen c th tng trong nc tiu v trong cc vi qun mt
urobilinogen cng b ng gan v trn vo mu ra nc tiu. Stercobilinogen trong phn
s gim.
Hnh 8.9. Qu trnh thoi ho ca Hemoglobine
Vng da do nguyn nhn sau gan. Trong cc trng hp ny, qu trnh tan huyt bnh
thng, chc nng gan bnh thng nhng mt khng c xung rut nn gy vng da do
nguyn nhn sau gan, l cc nhm bnh si mt, u u ty, u mc treo v.v lm tc ng
mt ch. Trong trng hp ny, bilirubin lin hp b ng trong gan, mt v tro vo mu
lm tng bilirubin huyt thanh ch yu l bilirubin lin hp. Nc tiu trong cc trng hp
ny xut hin nhiu sc t mt km theo mui mt, urobilinogen c th tng do trong gan v
tro vo mu xut hin nhiu trong nc tiu. Stercobilinogen gim trong phn lm phn bc
mu.
8. Sinh tng hp protein
8.1. ngha ca qu trnh
Sinh tng hp protein l mt qu trnh c vai tr quan trng bc nht i vi i sng
sinh vt, v thng qua cc cht sng c hnh thnh (enzyme, khng th, hormone...) qua
qu trnh ny ta hiu c bn cht ca di truyn, bn cht ca loi ging, ca qu trnh to
khng th, qu trnh sinh trng, pht dc ca ng vt. y l mt trong ba ni dung chnh
ca sinh hc phn t hin i (nng lng sinh vt, trao i acid nucleic v sinh tng hp
protein). V c ch sinh tng hp protein c 2 l thuyt l sinh tng hp theo khun mu v
sinh tng hp theo h thng a enzyme
8.2. Sinh tng hp theo khun mu
Khun mu tng hp protein l acid nucleic, vn mu cht ca n l to lin kt
gia cc acid amin mt cch c trnh t nht nh. Tng hp theo khun mu c 2 bc ln:
Bc 1 l qu trnh sao chp m di truyn.
Bc 2 l qu trnh phin dch m di truyn.
Ni dung chnh ca ton b qu trnh l nhm bo m thc hin chnh xc s lin kt
cc gc acid amin vo trong cu trc bc I c trng cho tng loi protein m t bo cn tng
hp.
8.2.1. Qu trnh sao chp m di truyn
Di truyn l s duy tr h thng protein t i ny sang i khc m thc cht l duy tr
cu trc bc I ca protein, tc l v trnh t lin kt v s lng cc acid amin trong chui
peptide. M di truyn c ghi chp trong DNA ( VSV cha c DNA th c ghi RNA).
Quy tc ca di truyn l mt gen m cho mt protein (mt nhim sc th l mt DNA). Tng
s gen gi l genom (s lng gen). Genotyp l kiu gen v pheotyp l kiu hnh (biu hin
bn ngoi ca kiu gen).
Trong mt m th 2 nucleotide u c ngha quyt nh, nucleotide th 3 c th thay
i (iu ny gii thch c 64 m), mt m gi l mt codon. Ta c th hnh dung qu trnh
sao chp theo s sau (hnh 8.11).
Qu trnh sao chp m di truyn v bn cht c th coi l qu trnh sinh tng hp RNA
thng tin (m-RNA). Qu trnh ny c thc hin trong nhn t bo ng vt c nhn v
trn DNA sinh vt cha c nhn, qu trnh ny c thc hin bi enzyme RNA
polimerase, mun cho enzyme ny thc hin phi tch i DNA nh yu t gii xon v ct
dy ni, sau nh yu t (hnh 8.13). Yu t bm vo mt trong 2 chui cho enzyme
RNA polimerase bm vo tin hnh sao chp. Trong qu trnh nhn i DNA 2 chui c gi
tr nh nhau, cn trong qu trnh sao chp th mi chui c gi tr khc nhau, nh vy enzyme
bm vo chui no l do yu t iu khin theo yu cu cn tng hp protein ca t bo.
Bn m gc Codon Anticodon
- T - A U
- C ===> - G C
- A - U A
DNA m- RNA t- RNA
Hnh 8.11. S trnh sao chp m di truyn
Lung thng tin di truyn ca sinh vt nh sau:
ADN ARN Protein
ADN ARN Protein
( Crik, 1967)
(Temin,1970)
Qu trnh sao chp t RNA sang DNA gi l qu trnh sao chp ngc. sinh vt nhn
x (procaryote) ch c 1 loi Enzyme RNA polymerase ph thuc DNA thc hin s sao
chp. sinh vt nhn chun (Eucaryote) c 3 loi RNA polymerase, mi loi c mt chc
nng ring. S sao chp RNA ch thc hin trn mt si ca DNA lm khun mu, hng sao
chp t 5-P n 3-OH. RNA-Polymerase xc tc tng hp RNA t cc ribonucleotide 5-
phosphate (ATP, GTP, UTP v CTP). S tng trng si RNA bng cch kt hp cc
ribonucleotide u 3-OH ca chui RNA (hnh 8.12).
(MMP)
n
+ NTP ---> (MMP)
n+1
+PP
RNA Ko di RNA
Mi mt nucleotide lin kt to thnh m- RNA c la chn theo nguyn tc b
xung gc kim ca Watson-Crick. Uridine (U) trong RNA i din vi adenine (A) trong
Hnh 8.12. S sao chp RNA
khun DNA, Adenine i din vi thymine, guanine v cytosine trong DNA i din vi
cytosine v guanine trong RNA.
Si DNA dng lm khun cho tng hp DNA gi l si khun hay si tr (-).
Khc vi DNA polymerase, RNA polymerase khng cn mm khi u tng hp. S
khi u tng hp mt on c bit gi l gen khi u (RNA c tng hp vn c 5-
triphosphate) gc GTP v ATP trong qu trnh phin m). Trong qu trnh phin m to
thnh on xon kp gia RNA v DNA khun gi l on xon kp lai RNA-DNA (hnh
8.13a). RNA trong si xon kp ny sau c tch ra khi DNA.
S tng hp RNA xy ra trn mt si DNA, nn si xon kp DNA phi tho xon,
vng tho xon phin m nh l bong bng. E.coli vng ny khong 17 cp base c
tho ri. S tho DNA pha trc v cun li pha sau. Qu trnh ny lm cho phn t
DNA quay ng k (hnh 8.13b), nu quay v pha trc chui l siu xon dng, v nu
quay v pha sau l siu xon m. E.coli s phin m vi tc 50 nucleotide 1giy.
Hnh 8.13. S phin m bi RNA polymerase trong E.coli
Cu trc v hot ng ca RNA polymerase.
Ecoli RNA polymerase n ph thuc DNA tng hp cc loi RNA kh ln (KLPT:
390.000) phc cht Enzyme ny c 5 tiu n v l li Enzyme v mt tiu n v th 6 l
(xch ma) hay 70 (KLPT: 70 000) n lin kt tm thi vi mt li v hng dn Enzyme
n v tr khi u c bit trn DNA, 6 tiu n v ny to thnh holoEnzyme RNA
polymerase (hnh 8.14)

Tiu n v
Yu t cn gi l yu t khi ng (yu t mi) gn vo RNA polymerase nhn
bit m (codon) khi u sao chp. Khi bt u sao chp n s tch ri yu t (r) cn gi
l yu t kt thc. Khi kt thc th yu t c gii phng (hnh 8.15). RNA polymerase
trt trn DNA tng hp RNA theo hng 5p n 3OH. n v tr kt thc, yu t gn
vo RNA polymerase nhn bit m kt thc sau yu t c gii phng, RNA
polymerase tch khi si khun DNA.

Li Enzyme
KLPT: - 36.500, - 151.000,
- 155.000
- 11.000, - 70.000. Tiu phn c cho
rng l v tr xc tc tng hp m- RNA
Hnh 8.14. HoloEnzyme RNA polymerase.
Vng khi ng:
S khi u tng hp m-RNA trn phn t DNA l vng c bit, vng phn t
RNA polymerase lin kt vi DNA v c gi l gen khi u. vi khun gen khi u l
2 on ngn vi khong 10 v 35 cp base. m-RNA lun lun to ra AUG khi u, pha trc
AUG c 1 on khng ghi m cho protein no c, ch gn vo ribosome (hnh 8.17).
DNA trong tt c cc t bo, cc m bo trong mt c th u ging nhau, nhng mi
m bo tu theo chc nng ca n m mt on gen no c hot ng. y l c s ca
qu trnh nui cy t bo cho pht trin thnh mt c th v l cch gi ging tinh khit nht.
Sau khi sao chp xong s tin hnh vic sa ct cc phn khng c ngha thnh m-RNA
hon chnh ri c a ra t bo cht cng vi riboxom tng hp protein.
Cu trc ca m-RNA khi mi tng hp nh sau ( hnh 8.16).
Intron

G
7
PPP --- CAP------ ------- ----------polyA
Extron
Hnh 8.16. M hnh cu trc ca m-RNA khi mi tng hp.
Trong : G
7
l u 5
P c G c metyl ho v tr 7 v c 3 gc phosphate. CAP

(m) l on polyme gn vi protein iu tit qu trnh sao chp. Intron l on v ngha.
Extron l on c ngha. Codon kt thc l UAG, UAA, UGA.
Hnh 8.17. Cc giai on trong s khi u phin m bi RNA polymerase E.coli
8.2.2. Qu trnh phin dch m.
y l qu trnh chuyn ni dung ca ngn ng acid nucleic m-RNA sang ngn ng ca
acid amin. Thc cht ca qu trnh ny l tng hp chui peptide trn khun mu ca m-
RNA. Qu trnh ny bao gm mt s giai on sau:
8.2.2.1. Hot ho acid amin
Mi cht mun i vo chuyn ho u phi c hot ho, enzyme thc hin qu trnh
hot ho acid amin l aminoacyl-t-RNA-syntetase, cn gi l codase. Codase c tnh c hiu
rt cao ti hng ng phnquang hc. Codase c 2 trung tm hot ng, qu trnh hot ho
acid amin ( hnh 8.19). Qu trnh din ra lm 2 bc:
b/ Chuyn aminoacyl sang t-RNA tng ng: Sau khi hot ho acid amin, enzyme
codase tm trong t bo loi t-RNA tng ng v gn acid amin vo , to thnh phc hp i
vo riboxom. (Trong t bo t nht c 20 loi t-RNA tng ng vi 20 acid amin). t-RNA c
cu to hnh c 3 l (3 thu) khong 68-100 gc base, c ui 3
OH bao gi cng l C-C-A,

acid amin s c gn vo ui ny (gi l thu acid amin), c mt thu gm AGC l ni
bm vo riboxom, mt thu c T
C (Timin Pseudo uridine Cytidin) gip cho t-RNA nhn

bit riboxom ang hot ng cn acid amin no v mt thu gia c 3 base l anticodon (hnh
7.18).
Hnh 7.18. M hnh cu trc ca t-RNA
Qu trnh chuyn aminoacyl sang t-RNA tng ng theo phn ng nh sau:
Aminoacyl-AMP + t-RNA tng ng -- > AMP + Aminoacyl-t-RNA (hnh 7.19)
Hnh 8.19. S hot ho acid amin
8.2.2.2. To phc hp khi u
Cc thnh vin ca phc hp khi u:
Riboxom l tiu th c khp mi ni tng hp protein ca t bo. V cu to: riboxom
l mt phc hp gm RNA + protein, kch thc c hnh mo m, ng knh gn 200A
0
gm 2 tiu phn, mt tiu phn ln 50S nhm Prokaryoter (VSV v ty lp th ca sv cao
ng) v 60S nhm Eukaryoter (sinh vt nhn chun) v tiu phn nh tng ng l 30S
hay 40S (hnh 8.20). Khi 2 tiu phn ny gn vi nhau to thnh riboxom hot ng 70S hay
80S. Loi 70S r-RNA chim 65%, loi 80S l 50%, phn protein ch yu l histon v
protamin, khi lng phn t loi 70S l 1-2 triu dalton, loi 80S l 4-5 triu dalton.
Trong t bo trng thi ngh, 2 tiu phn tch ri nhau, trng thi hot ng 2 tiu
phn lin kt vi nhau thnh mt khi, s lin kt ny theo kiu bn l. Mt tip xc gia 2
tiu phn l ni thc hin tng hp protein, trn c 2 khu vc. tiu phn 30S c mt khu
vc hnh thnh bi 17 protein v r- RNA gi l trung tm A, y l ni din ra qu trnh tip
nhn aminoacyl-t-RNA t t bo cht vo. tiu phn 50S c mt khu vc c cu to bi 7
protein v 7 r-RNA gi l trung tm D ( hay trung tm P) gi vai tr n nhn on peptidyl
ang c hnh thnh t A sang, mi ln to lin kt peptide mi th t y on peptidyl ny
s c a sang khu vc A, c bit khu vc ny c protein k hiu M11 lm nhim v
chuyn peptide (c chc nng ca enzyme transpeptidase).
Ngoi ra cn c rt nhiu cation cn cho hot ng ca riboxom nh Mg
++
, Mn
++
, NH
4
+
v mt lot cc poliamin nh spermin, spermidin, n cn cho s n nh cu trc gia RNA
vi protein trong riboxom.
V chc nng hot ng, riboxom hot ng trong t bo ging nh mt ci my ch
khng phi mang tnh cht enzyme (tc l c s chuyn dch trong khng gian).
tham gia qu trnh to phc hp cn c mt lot cc yu t khi u: t bo cha
c nhn (Prok) gm cc yu t IF
1
khi lng 8000 dalton, IF
2
75.000 dalton, IF
3
30.000
dalton (IF: Imidiaton factor: sng kin, m u). t bo c nhn (Euk) l M
1
, M
2
, M
3
.
Khi c tn hiu tng hp protein th IF
3
bm vo tiu phn 30S, ti ch m ribosome
30S tip xc vi Ribocom 50s, n lm thay i cu trc ca tiu phn 30S, to iu kin cho
IF2 bm vo v to thnh phc hp gm I F 2 Met - t-RNA
i
Mct
GTP, I F3, Ribosome 30S
(hnh 8.21)
Phc hp trn gn vi m-RNA to phc hp tin m u. IF1 v protein gn m CBP
(cap binding protein) gip vic t thng tin trn ribosome 30S ng hng ca m u
5P. Trong qu trnh ny ATP thy phn qut thng tin n v tr trn ribosome 30S. S
qut thng tin tin hnh t u 5P qua khong xp x 100 nucleotide trn b ba AUG. Thng
thng th b ba u tin AUG c s dng l m m u phin dch nhng i khi cc
nucleotide on ph cn khng ph hp cho s m u th phi n m AUG tip theo.
Nh vy IF
1
vo lm cho m-RNA v aminoacyl-t-RNA u tin bm vo trung tm A.
Aminoacyl u tin bao gi cng l Met c phocmyl ho. Vic phocmyl ho c
tc dng bt kn nhm -NH
2
trnh khng gy nhm ln trong vic to lin kt peptide u tin,
ng vt c nhn khng cn qu trnh ny v hot ng ca n nh hng r rt (hnh
8.22).
Hnh 8.20. Cu trc ca Ribosome
Hnh 8.21. Giai on m u tng hp protein t bo cha c nhn
CH
2
- S - CH
3

CH
2

CH

C=O NH - CHO

O - t- RNA Hnh 8.22. Focmyl metionin
Hnh 8.20. Cu trc ca ribosome
Khi focmyl MET vo th GTP vo v IF
3
ra lc ny IF
2
hot ng n phn gii GTP
thnh GDP + P
i
v nng lng. Nng lng ny c dng vo vic y IF
1
ra ngoi v gn
cht 2 tiu phn 30S v 50S vi nhau, y m-RNA ln 1 bc (1 codon), IF
2
ra ngoi v Met
focmyl c chuyn t 30S sang 50S ( t khu vc A sang khu vc P) (hnh 8.21).
8.2.2.3. Qu trnh ko di chui peptide
Qu trnh ny cn cc yu t sau:
Yu t ko di bao gm: EF-Tu, EF-Ts ( VSV); TF
1
( t bo c nhn) cc yu t ny
dng cho lin kt.
Yu t i ch EF-G ( VSV); TF
2
( t bo c nhn).
Qu trnh din ra theo chu k gm 3 bc sau:
Lin kt: T t bo cht cc aminoacyl-t-RNA ln lt i vo riboxom nh yu t vn
chuyn EF-Tu (hay TF
1
), chng to thnh phc hp EF-Tu- GTP-aminoacyl-t-RNA. Phc
hp ny i vo khu vc A ca 30S, EF-Tu gip cho vic lin kt nh hng cho aminoacyl-t-
RNA vi codon ca n ng thi vi vai tr enzyme phn gii GTP cho nng lng. Nng
lng ny gip cho aminoacyl -t-RNA bm chc vo codon, sau EF-Tu v GDP+ P
i
i ra
ngoi, EF-Tu mun hot ng tr li phi chu tc dng ca EF-Ts v nng lng ca GTP
(hnh 8.24).
Chuyn peptide: nh hot ng ca nhm protein M11 khu vc P n y acid amin
vo trc (F.Met hoc c on peptidyl) t khu vc P sang khu vc A ca tiu phn 30S v
mt lin kt peptide c hnh thnh y. khu vc P ch cn li t-RNA, qu trnh ny
khng tn nng lng. Kt qu ca bc chuyn ny l mt lin kt peptide c hnh thnh
khu vc A, t-RNA c gii phng khu vc P.
i ch: i hi yu t i ch EF-G (hay TF
2
) v nng lng ca GTP. Khi EF-G bm
vo riboxom n phn gii GTP cho nng lng, nng lng ny cn y t-RNA khu vc
P ra ngoi v ton b tng peptidyl -t-RNA t khu vc A sang khu vc P, ng thi m-RNA
dch ln mt codon, c ngha l khu vc A ca 30S li xut hin mt codon mi ng vi
mt acid amin mi sp a vo (hnh 8.23).
Qu trnh c tip din nh vy, trong qu trnh riboxom lin tip c ng m
ging nh mt my gip, mi ln gip th mt acid amin li c gn vo chui peptide. Qu
trnh ny tu theo s lng acid amin ca phn t protein ang c tng hp.
8.2.3. Giai on kt thc
Cc yu t kt thc: RF
1
, RF
2
, RF
3
y l nhng protein c khi lng phn t trung
bnh 40.000 dalton. RF
3
c chc nng xc tc RF
1
, RF
2
. Khi chui peptide hnh thnh
xong ng vi phn t protein m t bo cn tng hp th m-RNA cng c c gn ht v
qu trnh bc vo giai on kt thc, trn khu vc A xut hin cc codon kt thc UAA,
UAG, UGA. T t bo cht cc yu t kt thc c a vo riboxom, RF
1
nhn bit c
UAA, RF
2
nhn bit c UAG v chng u nhn bit c UGA. Cc yu t ny gip cho
qu trnh nhn bit c codon kt thc, di tc dng xc tc ca RF
3
cc yu t RF
1
, RF
2
,
hot ng v lin kt este ca acid amin cui cng b ct t, chui peptide ri khi riboxom,
t-RNA cui cng ri khi khu vc P v m-RNA ri khi riboxom, 2 tiu phn ca riboxom
tch ra khi nhau (hnh 8.25).
Chui peptide c ct b nhm phocmyl do enzyme dephocmylase ri sau ct b
u ui thnh chui peptide hon chnh, nh cc lin kt, lin kt nhnh ca cc acid amin
v cc ion Mn
++
, NH
+
... chui peptide t ng to thnh cu trc bc II, III...
Hnh 8.23. Giai on ko di chui polypeptide t bo c nhn
Hnh 8.24. Vai tr ca (EF1) trong chu trnh ko di.
Hnh 8.25. Giai on kt thc v tch ri.
8.2.4. Chui polypeptide gp li v hon thin.
Chui polypeptide sau khi c tng hp s tri qua mt qu trnh phn ng gi l s
bin i sau sao chp. c t bo khng nhn v c nhn, s bin i bao gm cc qu trnh
sau y:
i u C v N tn cng. Trong qu trnh tng hp chui polypeptide u c m u
bng F- Met t bo khng c nhn v Met t bo c nhn. Nhm formyl, Met v thng
thng thm mt s acid amin u N v u C b tch ri bi Enzyme.
Mt mt on du hiu (on trnh t tn hiu), khong 15-30 acid amin u N ca
mt s protein ng vai tr nh hng cho protein n ch ginh cho n trong t bo. Du
hiu ny c tch khi nh peptidase c hiu.
S thay i acid amin c th. Nhm OH ca mt vi acid amin nh Ser, Tre v Tyr ca
mt vi protein c phosphoryl ho nh ATP. Vic thm nhm phosphate lm cho
polypeptide mang in m. V d casein ca sa c nhiu nhm phosphate gn vi Ca
+2
. Tuy
nhin, s phosphoryl ho ca Tyr mt s protein li c lin quan n s chuyn ho t bo
bnh thng thnh ung th.
Nhm carboxyl cng c gn thm vo Asp, Glu ca mt vi protein, v d
prothrombine cha nhiu carboxyglutamate, ti mang in tch m v gn vi Ca
+2
nh
c tc dng lm ng mu. Mt vi protein c Lys c methyl ho bi Enzyme. Mono v
dimethyllysine c mt trong mt vi protein ca c v Cytocrom C.
Gn thm chui Carbonhydrat. Vic gn ny xy ra trong hoc sau qu trnh tng hp
chui polypeptide. V tr gn c th Asn, Ser hoc Tre.
Gn thm nhm Isoprenyl. Cc protein c s bin i ny thng l cc oncogen v
proto-oncogen (cc cht gy ung th v tin ung th).
Gn thm nhm ph. Cc protein gn thm nhm ph to thnh cc protein c hot tnh
sinh hc, v d biotin trong acetyl CoA carboxylase hoc Hem trong cytochrom C.
Hon thin bng cch phn gii: l trng hp ca cc zymogene hay Insuline.
S to thnh lin kt cho disulfide. Cc protein i ra ngoi t bo c nhn sau khi gp
li mt cch t ng, thng lin kt cho ng ho tr do s to thnh cc cu disulfide gia
Cys trong hoc gia cc chui. Qu trnh ny chng s bin tnh ca protein mi trng
ngoi t bo.
8.3. Tng hp protein ty lp th.
a s cc protein ty lp th c tng hp bo tng v c ghi thnh m trn
DNA. Nhng mt s protein, mt vi t-RNA, r-RNA c ghi thnh m trong gen ca ty lp
th. Midochondria c th tng hp protein c lp c RNA polymerase, aminacyl- t-RNA
synthe-tase, t-RNA v cc ribosome ring bit.
Qu trnh tng hp protein Midochondria cng ging nh cc qu trnh tng hp
protein m t. Song cng c mt vi kha cnh ng lu . Cc thnh phn nh: t-RNA,
aminacyl t-RNA synthetase, ribosome, cc tiu phn to thnh ribosome v.v.. th s lng t-
RNA t hn, b m cng c mt s im khc bit. Ribosome ca Midochondria th nh hn,
r-RNA ngn hn ca bo tng v ca t bo khng nhn. Phc m u tng hp protein ty
lp th cng l f.Met-t-RNA. Tuy nhin vic hip ng s tng hp protein trong
Midochondria vi s tng hp protein bo tng s c cp ti phn Midochondria.
8.4. iu ho tng hp protein.
8.4.1. iu ho hot ng ca RNA polymerase.
RNA polymerase gn vo DNA m u cho s sao chp mt on c bit trn DNA
c gi l Promotor. Promotor gn v tr RNA bt u tng hp trn DNA khun. S iu
ho m u sao chp l mi quan h gia RNA polymerase v promotor. t bo khng
nhn nhiu gen c iu ho trong mt n v gi l OPERON. Mt Operon bao gm 2
vng: Vng iu ho v cc gen cu trc. Cc gen cu trc l nhng on lm khun sao
chp cc m-RNA. Vng iu ho gm Promotor, operator v cc v tr iu ho.
Sau m u sao chp c iu ho bi s kt hp ca protein vi promotor. C th
chia thnh 3 loi protein iu ho s m u sao chp bi RNA polymerase.
Yu t c hiu lm thay i tnh c hiu ca RNA polymerase gn vo hoc ri
khi promotor.
Yu t km hm gn vo Promotor, ngn chn s gn ca RNA polymerase vo
Promotor.
Yu t hot ho gn promotor, tng cng hot ng ca RNA polymerase.
Nghin cu u tin v s iu ho tng hp protein Enzyme l gen galactosidase
Bacteria cho php Bacteria ng ho lactose (hnh 8.26).
Hnh 8.26. C ch iu ho tng hp Galactosidase
C ch iu ho Operon Tryptophan.
E.Coli c nui cy trong mi trng c Tryptophan th E.Coli khng tng hp Try.
Nu mi trng nui cy khng c Try hoc c mt lng Try khng tng xng vi nhu
cu, Operon Try hot ng bnh thng, Try c tng hp, cn trong mi trng nui cy
c nhiu Try th Try gn vo repressor lm thay i cu hnh repressor, lc ny repressor li
gn vo operator, v tr ny gi ln promotor v s gn ca repressor ngn cn s gn ca
RNA polymerase 5 gen cu trc khng hot ng sao chp ra cc m-RNA m ho cho cc
Enzyme tng hp Try (hnh 8.27).
Ngoi hai c ch trn cn c c ch lm suy yu s sao chp v c ch SOS (cp cu
ngng ngay s sao chp).
Hnh 8.27. C ch iu ho tng hp tryptophan E.Coli.
8.4.2. Protein iu ho.
Cc protein iu ho c cc tnh cht sau:
C kh nng c nh trn DNA gn gen cu trc.
C kh nng ngn chn hoc hot ho s sao chp ca cc gen cu trc bng cch thay
i hot ng ca RNA polymerase.
C th tr li nhng tn hiu xut pht t ngoi hoc trong t bo. Nh m cc
operon khng hot ng hoc hot ng sao chp ra cc m-RNA. C nhiu dng cu trc ca
protein iu ho.
8.4.3. iu ho hot ng gen t bo c nhn.
cc t bo c nhn cng nh t bo khng nhn, s m u sao chp t mt im
iu ho hot ng ca gen. cc t bo c nhn thng iu ho bng cch tng cng hot
ng. Trc ht, s hot ng sao chp l kt hp gia nhiu s thay i trong cu trc ca
chromatin (cht nhim sc) trong vng sao chp. Th hai l thng qua nhng yu t iu ho
dng v m bit. Thng th iu ho dng chim u th. V th ba l c s khc bit
v mt vt cht gia qu trnh sao chp xy ra trong nhn t bo vi qu trnh phin dch xy
ra bo tng.
Mt protein iu ho c th tc ng ln nhiu gen v mi gen li c th chu nh
hng ca nhiu protein iu ho. Cc protein iu ho nhn bit chnh xc DNA v c nh
vo DNA nh cc dng cu trc c bit ca n to thnh cc vng c nh. Ti cc
protein iu ho s lin kt vi cc v tr tng ng trn DNA bng nhng lin kt yu nh
lin kt Hydrogen, lc ValderVal... Trong cc vng tc ng, chnh vng ny hot ho RNA
polymerase.
9. S hon thin phn t protein sau khi c tng hp.
Mt s protein sau khi ra khi Ribosome c hot tnh. Tuy nhin, nhiu protein li
cn s bin i sau phin dch. Nhng bin i ny l kt qu ca s hot ho tr thnh
dng c chc nng trong thnh phn ca cc bo quan trong t bo. Chng ta cng thy
rng cu trc bc mt ca protein c xc nh ngay t giai on sao chp (giai on tng
hp cc RNA thng tin). Cu trc y ca protein p ng nh mt c cht chu tc ng ca
cc enzyme chuyn ho, hoc iu khin n cc bo quan ca t bo nh t bo cht, ty lp
th, nhn hoc bi tit ra ngoi t bo. i vi cc protein t bo cht th n gin v chnh
chng c tng hp. Cn vi cc protein khc chng thng bin i theo cch ct ngn
v c vn chuyn ti cc v tr ring trong t bo. S vn chuyn ny lin quan ti mt
protein nh hng. Yu t quan trng nht ca s nh hng l mt on ngn trt t sp
xp ca cc acid amin cui N ca chui polypeptide mi c tng hp c gi l trt t
tn hiu (TTTH) (hnh 8.28).
Chc nng ca TTTH c David Sabatini v Gunter Blobel gii thiu t nm 1970.
TTTH c tc dng ch o protein n ng v tr trong t bo v c ri khi trong qu trnh vn
chuyn hoc khi protein n ni d nh.
10. S bin i ca mt s protein xut ngoi.
Protein dnh cho xut ngoi c tngn hp trn ribosome mng li ni cht c ht. S tng
hp ca chng bt u trn ribosome bo tng t do. Cc giai on ca s tng hp din ra theo
cch thng thng. Protein bi tit c cha mt on TTTH. on TTTH c hnh thnh li
ni bo ER. N nh du s chuyn v tr vo phn lumen (khoang) ca ER. Cc TTTH c sp
xp lun lun gn u cui N ca protein. Trong qu trnh tng hp, on thot khi Ribosome
sm hn. C khong hn 100 on TTTH c xc nh. on TTTH thng c chiu di
khong 15-36 acid amin, trn c cc on c trng khong 10-15 acid amin k nc, mt hoc
nhiu hn acid amin tch in dng thng gn u cui N ng trc cc acid amin k nc v
mt on ngn v pha u cui C (v tr ct) l cc acid amin ngn nh Gly, Ala (hnh 8.29 a,b).
Hnh 8.29 a. Tng hp v bi xut protein tit
Hnh 8.29 b. Tng hp protein mng sinh cht
on TTTH c tng hp trn Ribosome gn vo ER. TTTH l cng c trong vic nh
hng Ribosome vo ER. TTTH xut hin sm trong qu trnh tng hp v n gn u cui N.
Khi TTTH thot khi Ribosome th TTTH v Ribosome t n nhanh chng gn vi du hiu nhn
bit phn t Signal recognidion particle (SRP). SRP c to thnh do 6 protein khc nhau v
phn t RNA 7S. SRP ch gn tm thi trong qu trnh tng hp protein. Khi peptide c khong 70
acid amin th ngng gn. SRP cng gn vi Ribosome. Ton b phc hp ny c gn vi
Receptor. SRP v Receptor Ribosome trn b mt ca ER. Chui polypeptide mi sinh c giao
cho phc hp chuyn v tr peptide trn ER. SRP ri khi Ribosome v tip tc mt chu k mi.
Phc hp chuyn v tr nui dng cho chui polypeptide pht trin ko di trong lumen ca
ER.TTTH b tch ri bi enzyme thu phn tn hiu trong lumen ca ER. trong lumen, protein
mi s bin i theo cc con ng ring: To thnh cc lin kt disulfide cng nh nhiu protein
s glucid ho (hnh 8.30).
Hnh 8.30. a protein mng chuyn ho vo mng li ni cht. (a)protein mng c
th ct b ui tn hiu cui N v ui Stop- transfer; (b) protein mng type II ui tn hiu cui
N khng c loi b; (c) protein mng type III c ui tn hiu multiple v Stop- transfer.
11. S Glucid ho ca protein.
Qu trnh ny xy ra trong li ni bo v trong phc hp Golgi. S glucid ho ny quan
trng v 2 l do: Th nht n lm thay i hot tnh sinh hc, thay i tnh ho tan, tnh n nh v
tnh cht vt l ca protein. Th hai chnh nhm carbohydrate ca glucoprotein cng c tc dng
nh mt du hiu nhn bit v tr m protein nh v. S glucid ho khng ph thuc vo b ba
m di truyn. V tr glucid ho ph thuc vo nhng acid amin thch hp trn phn t protein v c
tnh ca enzyme vi c cht c glucid ho. S glucid ho protein c nhiu loi
glycosyltraspherase tham gia (khong trn 100).
Trong protein c glucid ho cc oligosaccharide thng c lin kt vi protein thng qua
Asn. Cc lin kt N- oligosaccharide c hnh thnh bng nhiu cch, nhng c chung bc u
tin: 14 n v oligosaccharide bao gm 2 phn t N- acetyl glucosamine, 9 manose, 3 glucose
c vn chuyn t dolichol phosphate mang n tng phn t Asn trn protein.
oligosaccharide c gn vo nhm phosphate ca phn t dolichol phosphate bng cch gn
ln lt, gn tng monosaccharide. Th oligosaccharide hon thin nh h thng enzyme
transferase vn chuyn t dolichol phosphate sang protein. Cc transferase nm trn mt lumen ca
ER v chng khng xc tc qu trnh glucid ho cc protein ca bo tng. Sau khi vn chuyn vo
trong lumen th oligosaccharide c sp xp v tip tc bin i bng cc con ng khc nhau
vi cc protein khc nhau, nhng tt c nhng lin kt N- oligosaccharide vn c duy tr (hnh
8.31, 8.32).
Hnh 8.31. Tng hp oligosacchoride gn N trn cht mang dolichol phosphte mng RER.
Hnh 8.32. Chuyn Oligosaccharide ti protein v cc qu trnh xa hn xy ra trn RER
v Golgi.
Protein ri khi ER n phc hp Golgi trong cc nang chuyn ch. Trn phc hp Golgi, cc
lin kt O-oligosaccharide c hnh thnh v lin kt N- oligosaccharide c bin i. Bng
nhng c ch ny cc protein bin i ph hp cui cng gi ng nh d nh.
Trong phc hp Golgi, cc protein c chuyn ra cho cc t bo bn ngoi qua mng bo
tng hoc lysosome. Hai cch vn chuyn khc nhau ny c phn bit trn c im cu trc
khng gian ba chiu ca protein, khc vi TTTH c tch ri trong lumen ca ER. Qu trnh
phn bit protein c bit r rng i vi Hydrolase, protein vn chuyn n lysosome. Cu trc
ba chiu ca Hydrolase i khi c gi l du hiu ghp ni, c nhn bit bi
Phosphotransferase, enzyme xc tc s phosphoryl ho mt vi mannose trong enzyme ca
oligosaccharide . S c mt ca mt hoc nhiu mannose 6- phosphate trong lin kt N-
oligosaccharide l du hiu cu trc chnh n hng protein n lysosome. Receptor protein trn
mng ca phc hp golgi nhn bit du hiu mannose 6- phosphate ny v gn vi hydrolase to
thnh phc Receptor hydrolase.Nhng nang cha phc hp Receptor hydrolase chuyn t Cis
sang Trans ca phc hp Golgi, bng con ng n nang ph hp.Ti y phc hp Receptor
hydrolase b tch ri do pH thp trong cc nang v bi s tch ri nhm phosphate ca mannose 6-
phosphate di tc dng ca phosphatease. Receptor quay tr li phc hp Golgi v nang cha
hydrolase t nang tng ng vo lysosome. Nh vy i vi hydrolase lin kt N- oligosaccharide
ng vai tr cha kho trong vic nh hng enzyme ny ti lysosome (hnh 8.33).
Hnh 8.33. Tng hp v nh hng protein Lysosome
12. Cc protein i vo ty lp th.
Cc protein c tng hp trong bo tng trn cc ribosome t do, sau c chuyn vo
ty lp th. Cc protein mi c tng hp c coi nh mt tin thn, c phn t ln. TTTH cui
N cung cp du hiu cho protein n ty lp th th cha c xc nh hon ton, nhng n giu
acid amin c nhm OH v thng thiu cc acid amin c tnh acid. TTTH ny c nhn bit bi
Receptor ca ty lp th c kh nng nh s gip ca yu t nhp khu (import factor). Cc
protein c chuyn v tr qua c hai mng vo trong Matrix (cht nn), sau cc protein ri khi
TTTH nhng trt t cc acid amin cn li khng thay i. Mt v d protein i vo ty lp th theo
kiu ny l Cytocrom b2. Cn Cytocrom C th li khc, n khng c tng hp di dng mt tin
thn c phn t ln, nhng li c TTTH nm trong cu trc ca Cytocrom C. Phn apoprotein ny
nm gn mt ngoi ca mng v i vo phn gia hai mng. Lin kt ng ho tr vi Hem v s
thay i cu trc lm cho n khng quay tr li bo tng (hnh 8.34).
Hnh 8.34. Chuyn protein ti cht nn ca ty th
13. Cc protein nhn t bo.
Nhn t bo nhn nhiu protein cu to ring cho nhn v cho cc qu trnh sao chp DNA.
mng nhn c cc l cho php cc protein phn t nh i qua. Cc protein u c on TTTH
c bit nh hng protein vo trong nhn t bo. on TTTH ny rt giu lysine v Arginine. Cc
Histon v Nucleosome c iu ho bi mt protein gi l Nucleoplasmine. Cc protein khc c
th c gi li trong nhn bi s to thnh nhng phc hp trong cc bo quan. on TTTH nh
hng cho protein n nhn, v d trt t cc acid amin (-Pro-Lys-Lys-Arg Lys Val-) nm trong
cu to phn t khng b tch ri. Du hiu ny cho php protein nh DNA polymerase, RNA
polymerase vo trong nhn nhanh chng qua cc l ca nhn.
Cu 1: c im trao i protit ng vt cao ng?
Cu 2: S tiu ho v hp thu protit ng vt?
Cu 3: Hy k mt s enzym tiu ho protit ng vt?
Cu 4: Phn ng kh amin (-NH
2
)? ngha ca phn ng ny?
Cu 5: Phn ng chuyn nhm amin (-NH
2
) trong axt amin? Vai tr ca phn ng
ny i vi s sng ca sinh vt?
Cu 6: Phn ng kh nhm carboxyl (-COOH) trong axt amin? Nu vai tr ca phn
ng ny?
Cu 7: Vng Ornitin v vai tr sinh hc ca n?
Cu 8: Trnh by qu trnh hot ho v to phc hp khi u trong qu trnh tng
hp protit theo khun mu?
Cu 9: Trnh by qu trnh ko di chui peptit v kt thc trong s tng hp protit
theo khun mu?
CHNG IX
MIN DCH HC
S sng trn tri t pht trin theo quy lut "cnh tranh", y cng l ng lc ca quy lut tin
ho, cho nn tt c mi c th u b tn cng lin tc bi c th khc. p ng li cc xm nhp,
c th ng vt pht trin nhiu chin thut bo v khc nhau. Cc vi sinh vt v vi rt khi vo
c bn trong c th gy ra nhiu bnh cho c th. C th ng vt tri qua s tin ho cch
thc bo v phc tp ca mnh m chng ta hiu l h thng min dch. Min dch theo ting
Latinh l immunis c ngha l c min (v d min dch i vi cc bnh u ma, si... khi tri
qua mc ln u hay c tim phng vaccin).
Cc mm bnh (Pathogen) trc ht vi phm hng ro vt l l da v mng nhy, y, n
c phn bit l vt xm nhp t bn ngoi v n s b tiu dit. Trong phm vi chng ny chng ta
s bn v h thng min dch v s nhn din cc vt xm nhp t bn ngoi vo cng nh s phn
bit chng vi cc thnh phn bnh thng ca c th, ri tiu dit n nh th no. H thng min dch
v h thng thn kinh ca ng vt c xng sng lun lun pht trin tng xng vi nhau.
1. H thng min dch ca c th (cc dng p ng min dch).
C 2 h thng min dch, l h thng min dch t bo v h thng min dch dch th.
Min dch t bo (Cellular Immunity) l s chng li cc t bo b thm nhim Virus, k
sinh trng, cc m l thng qua tc ng trung gian ca cc t bo lymphocyte.
Min dch th dch (Humoral Immunity) Humor l thut ng c ca th dch (Fluid), n c
hiu ng nht trong vic chng li s thm nhim ca vi khun v Virus, n c tc ng trung gian
bi rt nhiu dn xut chn lc ca cc protein c lin quan c hiu l khng th hay l cc globulin
min dch (Immunoglobulin - Ig). Cc khng th c to ra t cc t bo B, ng vt c v, cc t
bo ny c chn (mature) trong tu xng.
1.1. H thng min dch t bo (Cellular Immunity).
y l cch chng li cc t bo, vt l xm nhim vo c th nh vi rt, vi khun... thng qua
bn thn t bo c kh nng gy min dch c hiu, ngha l t bo kt hp vi nhng khng nguyn
tng ng c gn trn mt t bo khc.
Tnh min dch ca ng vt c xng sng l do nhng dng xc nh ca t bo mu chn lc
l cc lymphocyte. Chng c sinh ra nh tt c cc t bo mu bt ngun t cc t bo tin thn
thng thng (t bo ngun) tu xng. Tuy nhin cc t bo lymphocyte khc hn vi cc t bo
hng cu, n c th ri khi dng mu i vo khong khng ni bo ni c cc tc nhn bn ngoi
xm nhp, ng thi chng c th quay tr li mch huyt qun.
C 2 loi lymphocyte: lymphocyte T v lymphocyte B
1.1.1. Lymphocyte T.
Lymphocyte T c sinh ra tu xng, di chuyn v tuyn c (thymus) v thnh thc y,
sau vo mu, mt t vo hch lm ba. Lymphocyte T thnh thc cha c kh nng min dch, sau
khi c khng nguyn kch thch, n c hot ho tr thnh t bo lymphocyte T m, i vo lch
hoc hch lm ba, y chng tng sinh tr thnh lymphocyte T c kh nng min dch rt mnh. V
chc nng, ngi ta chia lymphocyte T ra thnh my loi sau:
T bo lymphocyte T hiu ng (effetor T, k hiu l Te hay cn gi l lymphocyte git- Killer
T (T
k
): chng c tc dng trc tip tham gia min dch t bo, c kh nng ph hu, phn gii vt l, t
bo ung th.
T bo lymphocyte T h tr (Helper T Cell k hiu T
H
): c tc dng hip ng vi bch cu
n nhn ln, xc tin hot ho t bo lymphocyte B.
T bo lymphocyte T c ch (Suppesor T k hiu T
S
): c vai tr c ch v hot ho t bo
lymphocyte B v cc t bo T khc, tham gia iu ho min dch.
T bo lymphocyte T nh (Memory T k hiu T
m
): c i sng di, nn khi gp khng nguyn
m n tip xc th tng sinh v p ng min dch mnh.
Lymphocyte T c quan h mt thit vi bch cu n nhn. Bch cu n nhn thc bo khng
nguyn, phn gii khng nguyn v tit vo mu nhng mnh phn t min dch, gy kch hot t bo
lymphocyte T. i lc khng nguyn (KN) kt hp khng th (KT) ngay trn b mt t bo n nhn
ln, sau tip xc vi t bo lymphocyte T, truyn thng tin min dch cho t bo lymphocyte T.
Ngi ta pht hin lymphocyte T h tr v lymphocyte T c ch mt s cht c tc dng
i vi lymphocyte nh:
TSF(Thymus stimuleative factor): Yu t kch thch t bo tuyn c.
T
c
GF(T cell growth factor): Yu t sinh trng t bo T.
V sau ngi ta t tn cho nhng yu t ny l interlukin-II (iL-2). Nhng cht ny c tc dng
lm tng sinh sn t bo T, iL-2 c tc dng hot ho t bo B, t bo T.
1.1.2. Lymphocyte B.
Lymphocyte B c sinh ra tu xng, thnh thc y hoc ti huyt (Bursa Fabricius)
ca gia cm. Chc nng chnh ca cc lymphocyte B l sinh ra cc khng th di s kch thch ca
lymphocyte T.
C mt s i thc bo (t bo dng bch tuc lch v hch lympho, t bo Langerhans di
da, t bo Kuffer gan) lm nhim v by v tp trung KN. Phn ln cc KN u b cc i thc bo
bt v x l, sau khi x l cc KN, i thc bo c nhim v trnh din cc KN cho lymphocyte T.
S p ng min dch t bo c hnh thnh do s c mt ca cc phn t l, cc protein v
acid nucleic m chng ta hiu l khng nguyn (antigen).
Qu trnh ny xy ra thng qua mt sery phc tp ca cc tng tc trung gian gia cc dng t
bo T vi cc t bo B gn c hiu mt khng nguyn (hnh 9.1). p ng min dch t bo dn n
s hu hoi cc t bo "phm ti". N c bt u khi mt i thc bo(macrophage) (1a, 1b) x l
mt khng nguyn l, khi c tiu ho mt phn ai thc bo phi by cc mu khng nguyn
trn b mt ca n (3a, 3b). Ngi ta cho rng cc mu khng nguyn c gn vi mt trong hai
dng protein b mt t bo, l phc hp ho hp t chc chnh - Major Histocompatibility Complex
(MHC) (c gi nh th v chng c phin m t mt dy gen MHC). MHC rt a dng (c nhiu
allele). Cc c th phn bit vi nhau bi protein MHC. V th MHC l cc marker ca cc c th.
Protein MHC lp I c mt trn b mt ca tt c cc t bo c nhn ca ng vt c xng
sng. i thc bo (Macrophage) c protein MHC lp I c nhn bit bi cc Receptor ca t bo T
(T Cell Receptor), cc Receptor ny c trn b mt ca cc t bo
Hnh 9.1. Cc con ng p ng min dch (Marrack v Kappler 1086)
T gy c cha chn (Immature Cytotoxic T Cell). gn vi Macrophage phi by khng nguyn
trn b mt, cc Receptor ny phi to c phc c bit gia khng nguyn vi Protein MHC lp I
(4a). D nhin khng c mt phn t n l no li c th lm c vic ny. Cng bng cch tng
t, cc Macrophage c mang trn mnh nhng mnh khng nguyn to phc vi Protein MHC lp II
li c gn vi cc t bo T gip cha chn (Immature Helper T cell - T
H
) c mang cc Receptor
cng h (Cognate Receptor) (4b). Chnh v h thng nhn bit phc tp ny trn b mt t bo T
trnh lng ph cho h thng min dch t bo khng tc ng trn cc ch khng phi l t bo (hnh
9.1).
Cc t bo T gn vi phc Macrophage phi by khng nguyn v Protein MHC s to cm
ng dy truyn, mt qu trnh c hiu l s la chn dng (Clonal selection) ln u tin Niel Kaj
Jerne, Macfarlane Burnet, Joshua Lederberg v David Talmadge m t vo nhng nm 1950. Kt
qu l ch nhng t bo T nhn dng c hiu cc khng nguyn xm nhp th mi c sn xut vi
s lng ln. S la chn dng xy ra l do mt macrophage khi gn vi mt t bo T s gii phng ra
mt yu t c tn l Interleukin (5a, 5b) n kch thch c hiu cc t bo T lm tng sinh v bit ho
(6a, 6b). Qu trnh ny cng c kch thch bi mt cht t tit (autostimulatory secretion) ca t bo
T gi l Interleukin 2 (hnh 9.1).
Ch c cc t bo T to ra c Receptor vi Interleukin 2 th mi gn c vi Macrophage
(7a, 7b) v vy n trnh c s tng sinh khng hn ch ca t bo T. Tuy nhin, mt s lng ln
cc t bo T c t bo chn (8a) th cc Receptor ca chng li l ch c hiu cho cc t bo tc
ch phi by c khng nguyn l v c protein MHC lp I, iu ny c xy ra sau vi ngy khi
khng nguyn xm nhp ln th nht. Cc t bo T gy c t bo hay cn gi l cc t bo T git
(Killer T): Chng gn vi cc t bo tc ch mang khng nguyn (9) v thi im tip xc n gii
phng ra mt protein FO - KD gi l Perforin nm trn cc t bo ch (10) to nn cc l trn mng
tng bo (hnh 9.1).
Chc nng ch yu ca h thng min dch t bo l ngn nga s tri rng ca s thm
nhim Virus bng cch git cc t bo tc ch b thm nhim Virus (Cc protein bao ly Virus
thng c phi by trn b mt ca mt t bo ng vt trong nhng giai on mun hn ca s
thm nhim Virus). Min dch t bo cng c tc dng chng li s thm nhim ca nm, k sinh
trng v nhng dng ung th xc nh. Nhng mt thc t l chc nng sng ca h min dch t bo
tr nn yu km hn v trong nhng nm gn y c s tri rng ca AIDS (Acquired Immuno
Deficiency Syndrome: triu chng thiu ht min dch mc phi) m tc nhn gy nn l HIV (Human
Immunodeficiency Virus: Virus gy thiu ht min dch cho ngi), Virus ny tc ng bng cch
tn cng c hiu vo Helper T Cell. H thng min dch t bo cng gp nhiu kh khn vi cc
thuc hin i khng c trong t nhin chng hn thuc trnh s loi tr m v cc t chc ghp t
cc donor bn ngoi. Nhng t chc ghp c nhn bit nh mt cht l v chng c protein MHC
khc vi Protein MHC ca tc ch. khc phc s loi tr mnh ghp ch c cch l pht trin cc
thuc km hm min dch (Immunosuppressant) nh Cyclosporin A v FK506, nhng cht ny ch km
hm p ng min dch nhng khng lm cho c th mt s bo v trc cc mm bnh khc.
1.2. H thng min dch th dch (Humoral Immunity).
Min dch th dch l cch min dch do cc t bo min dch tit khng th vo mu. Nhng
khng th ny s kt hp vi khng nguyn tng ng. y l cch min dch c hiu ng nht trong
vic chng li s xm nhim ca vi khun, vi rt..., n c tc ng trung gian bi rt nhiu dn xut
chn lc ca cc protein c lin quan c hiu l cc khng th hoc cc globulin min dch
(Immunoglobulin - Ig), cc khng th ny thng l do t bo lymphocyte B sn sinh ra trc s kch
thch ca helper T cell.
Cc t bo B c c Immunoglobulin cng nh protein MHC lp II (4c) trn b mt ca chng.
Nu mt t bo B chm trn vi mt khng nguyn gn vo mt Immunoglobulin c bit ca n th
s to mt phc (12) v khng nguyn c tiu ho mt phn (13) l cc on (fragment) trn b
mt ca phc hp vi protein MHC lp II (14). Cc t bo T gip chn (8b) c mang cc
Receptor c hiu vi phc hp ny s gn vo t bo B (15) v khi p ng th gii phng cc
Interleukin kch thch s tng sinh v bit ho t bo B (16). S phn chia t bo cn tip tc cho n
khi cc t bo B c kch thch bi helper T Cell (17), cc helper T Cell li ph thuc vo s c mt
lin tc ca khng nguyn (1b - 8b) (hnh 9.1).
Hnh 9.2. p ng min dch s cp v th cp
Hu ht hu du ca t bo B l cc t bo plasma (18) cc t bo ny chuyn ho tit
ra mt lng ln khng th c hiu khng nguyn. Khng th gn vi cc khng nguyn
(19), v th c th nh du n bng s ph hu theo kiu Phagocytosis (c tiu ho bi
bch cu gi l thc bo) hoc theo kiu hot ho h thng b th (mt dy cc protein tc
ng trung gian lm tan t bo v gy cc phn ng vim cc b).
Cc t bo B v T thng ch sng vi ngy tr phi n c kch thch bi khng nguyn thch
hp. Tuy nhin, s tng sinh ca t bo B li b gii hn bi cc tng tc ca chng vi T c ch (Ts)
- cng l mt hu du ca lympho T nhng c chc nng i nghch vi helper T Cell.
Mt nt rt c trng ca h min dch l mt sinh vt rt him khi b nhim 2 ln vi cng mt
mm bnh ging nhau hon ton, iu c ngha l s phc hi sau s thm nhim ca mt mm
bnh lm cho con vt min dch vi mm bnh . Ci c gi l p ng min dch th cp ny
c tc ng trung gian bi cc t bo T nh sng lu hn (11) v cc t bo B sng lu (20) khi
chm trn li vi cc khng nguyn cng h, c th 10 ngy sau th n tng sinh rt nhanh v t so
vi cc t bo T v B cn "trinh" (nhng t bo cha h chm trn vi khng nguyn) (hnh 9.1 v
9.2).
c tnh ny ca h min dch c nhn ra ngay t thi xa xa. Mt nh s hc ngi Hy
Lp tn l Thucydides ghi ch trn 200 nm nay rng: "Nhng ngi m khi c iu tr khi th
khng b mc li ln th 2 th bnh ".
1.3. H thng Min dch l h thng t dung np.
Hu ht cc i phn t sinh hc u c tnh khng nguyn. V th trnh s hu hoi h
thng min dch, ng vt phi phn bit r gia khng nguyn ca mnh v khng nguyn l. Qu
trnh ny c la chn mt cch tuyt i. i vi ng vt c xng sng c ti hng mi ngn
cc i phn t khc nhau m mi i phn t li c v s cc v tr khng nguyn khc bit.
Vy c ch ca s t dung np l g ? Nh ta bit h thng min dch ca ng vt tr nn
hot ho quanh thi im c ra. Nu mt khng nguyn l c cy vo phi trc lc th
ng vt khng c kh nng to min dch chng li khng nguyn . R rng l h thng min dch
loi i nhng dng t bo B hoc T nhn dng c cc khng nguyn c mt ng thi im
m h min dch tr nn hot ho (la chn dng). Tuy nhin, li c rt nhiu dng mi ca
lymphocyte m mi dng li c mt b gn nh c quyn v cc quyt nh khng nguyn c pht
trin ln trong i sng ca ng vt. Nh vy t dung np phi l mt qu trnh tin trin. Ngi ta
hiu rt r v c ch ca qu trnh ny, n xy ra tuyn c. Ch nhng t bo T trinh c mang
cc Receptor gn vi protein MHC nhng khng c i lc vi khng nguyn ca mnh th mi c
chn lc di truyn. Nh vy, ch c mt b phn rt nh lymphocyte c to ra bi tuyn c l ri
lin tc khi t chc . Nhng thnh thong h min dch cng mt dung np vi mt vi khng
nguyn ca mnh, kt qu l gy ra cc bnh t min v d bnh nhc c trm trng (Myasthenia
Gravis), mt bnh t min trong c th to ra cc khng th chng li cc Receptor ca
Acetylcholin ca c, xng (Acetylcholin l mt cht dn truyn thn kinh (neurotransmitter) lm cho
co c), kt qu l lm c b yu thi k phi cng nh cc giai on tip theo ca i sng sinh vt.
Cng tng t nh vy nhng ngi mc bnh lupus ban h thng (systemic lupus erythematosis)
l mt bnh vim thng xy ra thi k phi thai, c th to ra cc khng th chng li nhiu thnh
phn t bo ca chnh mnh, bao gm cc protein ribonucleate v DNA. Mt bnh t min thng gp
khc l bnh khp (h min dch tn cng vo cc ch khp ni ca m lin kt), hay bnh i tho
ng ph thuc Insulin (Insulin-dependent diabetes mellitus) v bnh a s cng (multiple sclerosis).
2. Cu trc v chc nng ca khng th (Immunoglobulin).
Khng th do Kitasato tm ra nm 1890 v ng nh ngha KT l globulin min dch
(Immuno globulin k hiu l Ig ). Khng th l thnh phn ca s bo v th dch lun lun c trong
huyt thanh ca ng vt v c tng hp nhiu khi gy min dch nhn to cng nh khi c bnh
truyn nhim. Bn cht ca KT l mt nhm globulin lm nhim v thc hin c ch " p ng min
dch "
Cu trc ca khng th: Theo Gerald Edelman v Rodney Porter, hu ht cc Immunoglobulin
v cc khi cu trc c bn ca n u bao gm 2 chui nh v 2 chui nng.
Chui nh (Light chain) k hiu L c khong 214 acid amin. Chui nh c 2 dng l K (Kappa)
v (lamda), c khi lng khong 23 KD
Chui nng ( Heavy chain) k hiu H c khong 446 acid amin, c khi lng khong 75 KD.
Chui nng c 5 loi:
M (Muy) tng ng c khng th IgM
G (Gamma) tng ng c khng th IgG
D (Delta) tng ng c khng th Ig D
E (Espilon) tng ng c khng th Ig E
A (Alpha) tng ng c khng th Ig A
Tng ng c 5 lp Immunoglobulin.
Cc subunit gn vi nhau qua cc lin kt disulfide cng nh hnh thnh cc tng tc khng
ng ho tr. K thut Electron Micrograph cho thy n l cc dimer (L - H)
2
hnh ch Y (Hnh 9.3,
9.3b). Immunoglobulin l cc glyco protein; mi chui nng c mt oligosaccharide.
ngi c 5 lp Immunoglobulin (Ig) c k hiu l IgA, IgD, IgE, IgG v IgM. Chng khc
nhau bi cc dng chui nng tng ng l , , , v (bng 9.1). C 2 dng chui nh l v .
Cc lp IgD, IgE v IgG ch tn ti dng dimer (L - H)
2
. Cn IgM l pentamer (hnh 9.4a), IgA c
th l monomer, Dimer v Trimer ca cc dimer ny (Hnh 9.4b). Cc Unit dng dimer ca cc
multimer c gn vi nhau bi lin kt disulfide v gn vi mt protein 20 - KD gi l chui J
(Joining chain). IgM ca t bo B cng c dng Monomer gn vi mng. l v tr gn khng
nguyn ca IgM monomer to cho IgM p ng min dch th dch.
Bng 9. 1. Phn loi cc lp Globulin min dch ca ngi.
Lp Chui nng Chui nh Cu trc di
n v
Khi lng
phn t
IgA or (
2
2
)
n
J
a
(
2
2
)
n
J
a
360 - 720
IgD or
2
2
160
IgE or
2
2
190
IgG
b
or
2
2
150
IgM or (
2
2
)
5
J
(
2
2
)
5
J
950
V cu trc ca khng th:
Nm 1959, Porter ch r rng, IgG - lp Ig ph thng nht khi b phn ct bi papain phn bn
l th ngi ta c 2 on Fab (Antigen binding Fragmet): on gn vi khng nguyn v mt on
Fc (Crystalizable Fragmet): on kt tinh. on Fc bao gm cc on cui C ca hai chui nng (Hnh
9.3a, 9.3b,). Fc c vai tr quan trng, tuy khng lm nhim v gn khng nguyn nhng Fc c kh
nng gn vi t bo khc v lm hot ho t bo n gn. on Fc cha cc v tr effector thc hin
chc nng thc bo, to phc vi b th v hng s vn chuyn ca cc Ig ti cc v tr tc ng ca
chng. Fc c receptor gn vo b th, ng thi Fc cn c vai tr lm nhim v thoi ho (phn gii
Ig khi kt thc nhim v).
Hnh 9.3a. Cu trc ca phn t Immunoglobulin (theo Dr Landry)
Hnh 9.3b. Cu trc ca phn t Immunoglobulin (theo Mike Clark, 1994).
Trong phn t Ig phn chui nh (L) li chia lm 2 phn: phn bin i (Variable) k hiu l
V
L
v phn c nh (Constant) k hiu l C
L
. chui nng cng c chia thnh 2 phn: phn bin
i (Variable) k hiu l V
H
v phn c nh (Constant) k hiu l C
H
. Phn bin i nm trong on
Fab, n c th bin i cho ph hp tng ng vi KN m n cn tc dng (hnh 9.3a, 9.3b, 9.4a,
9.4b).
Chc nng ca khng th: Nhng lp Ig tit khc nhau c cc chc nng sinh l khc nhau.
IgM c nhiu trong mu, c hiu ng nht i vi vic chng li s xm nhp ca cc vi sinh
vt. l mt Ig c tit ra u tin trong p ng vi mt khng nguyn; n c to ra sau 2 n 3
ngy khi c th chm trn ln u tin vi khng nguyn.
IgG l Ig ph thng nht, n c phn phi ng u trong mu v trong cc dch k. Ch c
khng th ny mi qua c nhau thai (qua Receptor mediated endocytosis) v th n cung cp tnh
min dch cho phi. IgG c to ra sau 2 n 3 ngy khi IgM xut hin ln u tin.
Hnh 9.4a. Cu trc ca Ig M

Hnh 9.4b. Cu trc ca IgA
IgA c nhiu trong ng tiu ho v trong cc cht tit nh nc bt, m hi, nc mt. IgA
chng li s xm nhp ca cc Pathogen bng cch gn vi cc v tr khng nguyn ca chng do vy
kho cht cc qu trnh gn vi b mt ngoi bin. IgA cng l mt khng th ch yu ca sa v sa
u. V th n gip cho tr s sinh chng li cc pathogen xm nhp bng ng rut.
IgE thng c mt trong mu vi nng thp, n c tc dng chng li k sinh trng v c
lin quan n cc phn ng d ng.
IgD cng c mt trong mu vi liu lng thp, chc nng ca Ig ny cha r.
Cc vng c nh v cc vng c th bin i ca chui nng v chui nh ca khng th.
xc nh c tnh ca mt phn t, iu cn thit l phi c c cc phn t tinh khit. i
hi ny l mt tr ngi ln i vi cc nh min dch hc. Khi mt con vt tip xc vi mt khng
nguyn c bit n hnh thnh v s dng t bo plasma, mi dng tng hp mt Ig gn khng nguyn
khc nhau cht t. V th khng th l khng ng nht. Tuy nhin, tr ngi ny c y lui vo
u nhng nm 1960 khi pht hin ra nhng c th c multi myeloma - mt t bo plasma ung th, n
tng hp mt lng ln cc mu n ca Ig c tn l Myeloma protein. Mt s myeloma to ra mt
lng tha cc chui nh, khi n c tit vo trong nc tiu th gi l protein Bence - Johnes (sau khi
Henry Bence Johnes pht hin ln u tin vo nm 1847).
Cc ui aminoacid ca mt vi protein Bence Johnes c cha 214 gc, ngi ta pht hin ra
rng s khc nhau v ui (trnh t) gia cc chui nh l nhng na cui N ca chng. Vng c th
bin i ca chui nh c cc gc tri t 1 n 108, c gi l vng bin i (Variable) k hiu l V
L
.
Cn vng c nh bao gm cc gc t 109 n 214 c gi l vng c nh (Constant) k hiu l C
L
(Hnh 9.3a, 3b,). Cng tng t nh vy, khi so snh vi chui nng myeloma c 446 gc th thy tt
c cc trnh t u khc nhau t gc 1 n 125. V vy chui nng cng c vng bin i V
H
v vng
c nh C
H
(Hnh 9.3a, 3b,).
Khi so snh cc trnh t cho thy vng C
H
bao gm 3 on gn 110 gc l C
H
1, C
H
2 v C
H
3
tng ng nhau v tng ng vi C
L
. Trn thc t ngay c trnh t ca vng c nh v vng bin
i cng c quan h vi nhau nhng xa hn so vi quan h gia cc thnh vin ca nhm ny. Khi
quan st mi n v ng dng c s lin kt cho bng cc cu disulfide chng t rng c 12 n
v ng dng (homology) ca mt phn t Immunoglobulin, mi n v c cun li trong mt vng
c lp. Nh vy r rng l cc gen ca chui nh v cc gen ca chui nng c tin ho qua s
nhn i ca mt gen gc m ho cho mt protein 110 gc. cc vng bin i V
L
v V
H
phn ln
cc amino acid bin i 3 trnh t bin i cao (hypervariable).
Elvin Kabat phn on rng cc trnh t bin i cao c lin quan vi v tr gn khng nguyn
ca Immunoglobulin v cc acid amin ca chng xc nh ch gn c hiu ca n.
Gii php ca Kabat c cc th nghim nh du i lc ng h. Cc phn t nh hn 5 KD
t th hin ch khng nguyn, nhng khi mt nhm hu c nh c tn l hapten chng hn nh nhm
2, 4 dinitrophenyl (DNP), nhm ny lin kt ng ho tr vi mt protein vn chuyn (carrier) chng
hn nh albumin huyt thanh b (do phn ng ca Fluorodinitrobenzene vi gc Lys ca n) v sau
c tim vo mt con vt th con vt ny s sn xut ra cc khng th gn vi hapten vi s c
mt ca Carrier. Nu mt cht tng t DNP chng hn nh p-nitrophenyldiazonium th n gn vi
khng th khng DNP nhm diazonium tnh phn ng cao ca hapten s hnh thnh lin kt diazo vi
His, Lys v Tyr chui bn trong vng ln cn ca v tr gn DNP ca khng th.
(DNP - hapten)

Hu ht cc chui bn dn xut nh thc t l cc thnh vin ca trnh t bin i nhiu ca
khng th. iu chng t rng cc v tr gn khng nguyn lin quan vi cc gc bin i nhiu.
on bin i ca Ig v th c gi l vng xc nh b cu (complementary determining regions-
CDR).
Hnh 9.5. Khng th ho tr 2 c th lin kt cho vi KN a ho tr to thnh mng li

Cc Immunoglobulin u gp li.
Cu trc ca Immunoglobulin c David Davie, Allan Edmondson, Robert Huber, Roberto
Polfak v nhiu tc gi khc xc nh v m rng bng phng php xc nh cu trc tia X- ca cc
on Fab v Fc. IgG l mt phn t c 2 phn tng ng ho hc, cc n v tng ng ca n to
thnh cc vng (domain) tch bit. Mi mt vng gn cht vi mt vng ca chui polypeptide khc
cho ton b phn t c coi nh l c cu to bi 6 module hnh cu, 2 module to nn ch Y
(vng Fc) v 2 to cnh tay X2 (vng Fab - Hnh 9.3a,9.3b)
Cc n v Immunoglobulin ng dng u c c tnh gp li ging nhau (Immunoglobulin
fold). Mt t hp bao gm mt tm i song song 3 v 4 si lin kt vi nhau bi lin kt disulfide.
Vng V khc vi Vng C ch yu bi vng polypeptide thm vo nm dc theo tm 3 si ca vng
V.
Nh cc nghin cu v ho hc sinh l v cu trc tia X cho thy cc Immunoglobulin c
tnh mm do cao gia cc on. Mt s kin c bit gi l vng "bn l" trong protein, on
polypeptide ny ni vi vng Fab v Fc ca n (Hnh 9.3a, 3b), tuy nhin, nhng vng ny ging ci
dy xch hn l mt ci bn l (trong 2 gc ca bn l l 65 v 115) c xc nh mt
cch chc chn.
Mt t hp bao gm mt tm i song song 3 v 4 si lin kt vi nhau bi lin kt disulfide.
Vng V khc vi Vng C ch yu bi vng polypeptide thm vo nm dc theo tm 3 si ca vng
V.
V cu trc c bn ca Immunoglobulin phi ph hp c vi nhiu khng nguyn v th tnh
mm do ca n lm thun li cho vic gn khng nguyn bng cch cho php mt s thch ng
gia cc khng nguyn v v tr gn ca n. Na phn t c Carbohydrate ca Immunoglobulin chm
gia cc n v ng dng CH
1
v CH
2
lm nhim v iu ho s tng tc gia cc vng Fab v Fc.
3. Khng th n dng.
Hnh 9.6. Cch to khng th n dng
Mong i ln nht l thu c cc Ig ng nht vi s lng ln bi mt dng lymphocyte.
Nhng tht kh l cc lymphocyte li khng pht trin lin tc khi nui cy. Mi cho n nhng
nm 1970, Sesar Milstein v Georges Kohler pht trin c k thut gy min dch cc dng
t bo ny (hnh 9.6). Cc khng th n dng c th thu c vi s lng khng hn ch v c
hiu cho hu ht cc khng nguyn bng cch trn ln cc t bo myeloma vi cc lymphocyte
c gy min, tc l to mt dng t bo lai. Cc t bo lai ny s tng hp c Ig ca
lymphocyte nhng li c tnh trng tn ca cc t bo myeloma.
Khng th n dng l mt cng c khng th thiu c trong y, sinh hc. Chng cng c
th dng thc nghim v phn lp mt lng cc k nh ca hu ht cc cht sinh hc c
hiu, chng hn nh chng ta c th lm c cc xt nghim Routine mu v s c mt ca HIV
m bo an ton trong vic truyn mu.
4. V tr gn khng nguyn ca khng th..
Cu trc tia X ca mt vi phc hp protein Myeloma - hapten ch ra rng v tr gn khng
nguyn ca Ig c nh v nh mi vng Fab trong mt khe nm gia cc n v V
L
v V
H
(Hnh
9.3a, 9.3b, 9.7)
Hnh 9.7. V tr gn vi khng nguyn ca khng th
Hnh dng v kch thc ca khe ny ph thuc vo trnh t aminoacid ca cc n v V
L
v
V
H
v cc bc thnh c to nn t 6 on bin i nhiu (CDR,). Chng c g phi ngc nhin l
cc phc hp khng th - hapten cng tng t nh cc phc hp enzyme - c cht. C 2 dng ny
u bao gm cc tng tc Valderval, lin kt k nc, lin kt hydrogen v tng tc ion. Tht vy,
cc phc hp khng th - hapten v phc hp enzyme - c cht u c cc thang tng t v hng s
phn ly t 10
-4
n 10
-10
M, n tng ng vi nng lng gn t 25 n 65 KJ.mol
-1
.
Cc phc hp khng th - hapten l nhng m hnh khng hon thin ca phc hp khng th -
khng nguyn bi v hapten ch lp y mt phn cc v tr gn khng nguyn tng ng. Tuy nhin
nhng khng th n dng c th gip cho vic xc nh cu trc tia X ca khng nguyn protein
trong phc vi cc dn xut Fab ca cc khng th n dng khng li cc khng nguyn ny. Chng
hn, nh cu trc tia X ca 3 phc hp lysozyme lng trng trng g (Hen egg white - HEW) vi cc
dn xut Fab ca cc khng th n dng anti - HEW lysozyme c xc nhn. Mi Fab u gn
kh c lp v hnh dng bt thng, mt ng c chiu di 700 A
o
trn b mt lysozyme, cc
chui bn nh ra ca mt phn t n rt khp vi ch lm xung ca rnh. Trong mi phc hp ny,
tt c 6 Fab CDR u tham gia gn lysozyme. Nhng phc hp ny rt ging cc phc hp protein -
protein bit, n c gn vi nhau do c s b cu cao v v th n ngn tr dung mi khi b tc
ng bi tng tc Valderval, cc cu nui v cc lin kt hychogen. Trong mt s tng tc ny, b
xng lysozyme v cc chui bn vn duy tr s phn bit cu trc, mt khc cng c nhng thay i
cu trc a phng (s so snh ny khng th m rng ti lysozyme gn Fab bi v vn cha kt tinh
c chng).
Tnh c hiu cao ca khng th anti-lysozyme i vi cc v tr khng nguyn c chng
minh bi hiu ng ca s thay i aminoacid n trn b mt tip xc ca lysozyme. Hng s phn ly
ca Immunoglobulin khng lysozyme HEW c tn l D1.3 vi lysozyme HEW l 2,2 x 10
-8
M. Nhng
hng s phn ly ca khng th n dng ny vi lysozyme lng trng trng li gn vi hng s phn
ly ca khng th n dng vi g g, chim ct v g ty l > 10
-5
M. Trong nhng lysozyme ny th
Gln 121 nh ra khi b mt lysozyme HEW v trong v tr gn khng nguyn ca Fab n c thay
bng His.
Vy c tnh c bit ca epitope (v tr khng nguyn) ni m khng th gn vo l g? Tt c
cc epitope lysozyme trn u gm 14 n 16 gc b mt t 2 hay nhiu on peptide. Mt s gc
ny biu l tnh di ng cao, nhng cc gc khc th khng. V th ngi ta ch thy 3 phc hp khng
th - lysozyme ph quanh mt na b mt lysozyme, iu chng t b mt tip cn y ca mt
protein l s tim tng tnh khng nguyn.
on Fab p ng gn khng nguyn nh th no? Cu tr li c xc nh nh nghin cu
tia X ca Ian Wilson, n ph thuc vo Fab v khng nguyn i hi. Khi so snh cu trc tia X ca
mt Fab t mt khng th n dng khng trc tip 1 on gm 36 gc ca Influenza hemagglutinin
ring r v phc hp mt on 9 gc ca khng nguyn th thy Fab gn vi i lc cao. iu vch
r rng khi gn vi khng nguyn lm cho Fab tri qua mt qu trnh sp xp li cu trc chnh -
ch yu thng qua s dch chuyn cu trc ca CDR3 chui nng. Nh vy, nu khng c s thay i
cu trc th Fab s khng c kh nng gn vi khng nguyn ny t nht l cu trc m n c tha
nhn trong phc hp ny. Mt khc, trong mt nghin cu tia X ca Wilson trn mt Fab khng li
trc tip on Myohemerythrin 19 gc (mt Fe khng hem cha protein gn oxygen ca mt u trng
bin) c dng n l ln dng phc hp vi khng nguyn th thy Fab ch tri qua s chnh l cu
trc mt vi chui chnh v chui bn khi gn khng nguyn.
Trong c 2 phc hp ang tin trin ny, cu trc ca Fab gn khng nguyn khc hn vi cu
trc protein dng nguyn th. iu ny lm ni ln tnh t m nhng vn cha tr li c l mt
khng th c th gn vi peptide v vi c protein hay l dn xut ca peptide ny nh th no? Nu
tr li c cu hi ny s xc nh c nhng hiu qu quan trng trong vic to ra cc vaccine c
s peptide.
5. S pht sinh tnh a dng ca khng th.
H thng min dch c kh nng to ra khng th khng li hu ht cc khng nguyn xm nhp,
n c th sn xut dng nh khng hn ch cc v tr gn khng nguyn khc nhau. Vy ci g l
ngun gc ca tnh a dng ny? Mt iu chc chn l biu l gen Immunoglobulin cng nh s biu
hin gen trong cc chui H v L rt tch bit ca cc protein c m ho bi mt gen nguyn bo
mm. Nu iu ny l s tht th cc gen ny c th phi m ho hng t cc khng th khc nhau.
ng vt c xng sng c kh nng to ra rt nhiu cc gen ny. Chng hn nh, cn phi c 10
3
gen
chui nng v chui nh m ho 10
3
x 10
3
= 10
6
Immunoglobulin khc nhau. Tuy nhin, cc nghin
cu lai to s dng cc si DNA ng v phin m mRNA ca Immunoglobulin ch r rng genome
phi chut ch cha mt vi gen Immunoglobulin, iu kh gii thch cho mc a dng ca
khng th quan st thy trong chut. Cui cng th ci gi l gi thuyt mm ny cng b gt b.
Hin nay c 2 m hnh v ngun gc tnh a dng ca khng th c coi l cng nhn, l:
5. 1. Gi thuyt ti t hp sinh dng (Somatic).
Gi thuyt ny do William Dreyer v Claude Bennett xng nm 1965 trn c s cho rng
tnh a dng ca khng th pht sinh bi ti t hp di truyn gia mt vi on gen c lin quan m
ha cho vng bin i ca Immunoglobulin. Qu trnh ny xy ra thng qua qu trnh ti t hp bn
trong nhim sc th trong thi k bit ho t bo B cho mi dng t bo biu l ch mt nhng c
quyn mt Immunoglobulin.
5. 2. Gi thuyt t bin sinh dng.
Gi thuyt ny cho rng tnh a dng ca khng th l do tc t bin cao ca gen
Immunoglobulin trong lc bit ho t bo B.
Chng ta s xem xt di y c 2 c ch to nn tnh a dng ca khng th.
5.3. Cc gen chui nh K c tp hp t 3 b cc mu gen.
Cc cng trnh nghin cu trnh t DNA ca Leroy Hood, Philip Leder v Susumu Tonegawa
ch r rng cc chui nh c m ho bi 4 exon (Hnh 9.7).
on dn hay on L
K
m ho mt peptide k nc c 17-20 gc. Peptide ny c tng hp
i vo mng li ni cht ri sau ct khi mng li ny.
on V
K
m ho 95 gc u tin ca vng bin i gm 108 gc ca chui K.
Chui ni (Joining) hay on J
K
(ng ln ln vi chui J ca IgA v IgM), m ho 13 gc
cn li ca vng bin i.
on C
K
m ho vng c nh ca chui K.
S sp xp ca cc extron ny trong cc m ca phi ngi (cha to c khng th) khc rt
nhiu vi h gen gp trc y. Cc on L
K
v V
K
tch bit nhau bi mt intron.
Tuy nhin, h gen chui K cng bao gm mt dy 150 cc n v L
K
- V
K
400-bp, tch bit
nhau bi mt ci chm 7 kb. Cc trnh t ca i exon ny nh sau theo th t thp dn: 5 on J
K

trung gian 300 bp, mt ci chm 2,4kb v mt on C
K
n l.
S lp rp ca mRNA chui K l mt qu trnh phc tp bao gm c ti t hp sinh dng v c
ni gen chn lc. i vi chut, bc u tin ca qu trnh ny xy ra mt t tin ca mi dng
t bo B, l qu trnh ti t hp bn trong nhim sc th ni n v L
K
- V
K
vi on J
K
v loi
b cc trnh t chen vo. Sau cc th h sau ny, cc gen bin i hon ton c phin m v
gp li mt cch chn lc, nh vy m ni n v L
K
- V
K
- J
K
vi on C
K
. Cc on L
K
v V
K
cng
gp li vi nhau trong giai on ny to nn mt mRNA m ho cho mt trong s cc thnh phn ca
Hnh 9.7. S t chc v sp xp li h gen
K chut
mt gen
chui nh (Hnh 9.7).
Cc trnh t bo tn cao u 3' ca mi on V
K
v u 5' ca mi on J
K
chng t cc
v tr ti t hp sinh dng c chn lc nh th no. on V
K
c tip theo sau bi mt trnh t
heptamer CACAGTG, mt ci chm 12 1 Nucleotide v mt nonamer giu AT b cu. Nhng trnh
t ny gn vi nhau di nh hng ca mt h enzyme ti t hp hnh thnh mt cu trc vng v
ng tc ng nh mt tn hiu ti t hp (Hnh 9.8).
5.4. S mm do ca ti t hp to nn tnh a dng ca khng th.
Khi ni mt trong s 150 on V
K
vi mt trong s 5 on J
K
c th to ra ch 150 x 5 = 750
chui K, con s ny t hn rt nhiu so vi s liu quan st c. Tuy nhin, nhng nghin cu
vch r n bao gm nhiu s kin xy ra nhng on V
k
v J
k
ging nhau. V tr ti t hp V/J
khng c xc nh mt cch chnh xc, hai on gen ny c th ni cc im bt cho khc nhau.
Sau na l cc amino acid c nh r bi cc m nm vng ln cn v tr ti t hp V/J ny ph
thuc vo phn trnh t ca on V
K
v J
K

dng mm.
Nh vy, cc amino acid c nh r bi cc m xung quanh ch ni ti t hp to nn vng
bin i nhiu ca chui nh ln cn gc 96 (CDR3, hnh 9.9). Phi tha nhn rng tnh mm do ti
t hp ny lm tng tnh a dng ca chui K ln 10 ln. Con s mong i v cc chui K khc
nhau c th ln ti 150 x 5 x 10 = 7500.
S ni khng chnh xc ca V/J thng gy nn s mt ngu nhin mt vi nucleotide cui
on V
K
v J
K
. Cui cng, trn 2/3 sn phm ti t hp b c lch pha (out of phase reading) v th
to nn mt gen m ho mt protein v ngha. Nhng protein ny s khng c biu hin. Mt t bo
trong mt s kin ti t hp khng to nn sn phm xy ra th s n lc sp xp li gen K xa
Hnh 9.8: H gen K dng mm c cha cc
heptamer v nonamer b cu, k tip l
on V
K
v trc l J
K
. Cc trnh t
ny l trung gian ti t hp sinh dng do
vic hnh thnh cu trc vng v ng
hn gia cc n v L
K
- V
K
cn li, nu tt c cc qu trnh ny tht bi th s sp xp li gen . Hin
tng ny chnh kin cho s quan st thy rng cc t bo biu hin K th rt him thy gen c
sp xp li. Trong khi , cc t bo biu hin th khng c s thay i sp xp li cc gen K.
Bng c ch ny c th pht hin c cc s kin ti t hp cha bit.
6. Cc chui nh .
H gen chui nh K v cc nhim sc th khc nhau c s sp xp li cc on L, V v C
cc dng mm khc nhau. chut ch c 2 on L
- V
, mi on c theo sau bi 1 cp n v J
- C
(Hnh 9.10). C l v th m chui nh K ca chut l 95% K v ch c 5% l . ngi th

ngc li, c rt nhiu n v L
- V
v J
- C
so vi chut; Immunoglobulin ngi cha mt lng

tng ng bng nhau gia cc chui K v
.
Hnh 9.10: T chc dng mm ca h gen chui chut, J
4
l on gen gi
7. S lp rp cc gen chui nng.
Cc gen ca chui nng c lp rp rt ging vi cc gen chui nh cng bi 4 on gen,
nhng li c thm phn diversity 13bp hay cn gi l on D nm gia cc on V
H
v J
H
.
H gen chui nng ngi nm mt nhim sc th khc vi h gen chui nh, n bao gm
cc cm ca 250 n v L
H
- V
H
, c th l 10 on D, 6 on J
H
v 8 on C
H
, 1 C
H
cho mt trong 8
lp hay di lp Immunoglobulin (Hnh 9.11).
Hnh 9.9: Cc im cho cc trnh t V
K
v
J
K
ti t hp sinh dng lm thay i mt vi
nucleotid v th to nn cc trnh t nucleotid
khc nhau trong gen K hot ng. V d amino
acid 96 vng bin i nhiu th 3 ca chui K
c th l Ser, Arg hoc Leu
Hnh 9.11: S t chc v sp xp li h gen chui nng ca ngi. Gia nh gen ny gm 250 i
trnh t ca cc on L
11
v V
11
, tip theo l ~ 10 on D, 6 on J
11
v 8 on C
11
. Trong khi
bit ho lymphocyte, mt n v L
11
-V
11
c ni ti t hp vi on D nm bn sn cc
on ngn ca cc trnh t ngu nhin c gi l vng N. c t bo B v t tin ca n, s
phin m v ni s gn cc n v V
11
-L
11
-N-D-J
11
vi mt trong8 on gen C
11
Cc on D m ho phn li ca vng bin i nhiu (hypervariable) th 3 ca chui nng. Dc
theo sn cc on V
H
, D v J
H
dng mm l phn tn hiu ti t hp heptamer - nonamer cng ging
nh chui nh (Hnh9.15). Tuy nhin, cc v tr ni V/D v D/J ca chui nng li tu thuc vo tnh
mm do ti t hp tng t nh cc v tr V/J ca chui nh. Qu trnh ni V (D) J ny c iu
ho cht ch, n xy ra theo th t thi gian c bit (tc l D
H
c ni vi J
H
trc khi V
H
ni vi
D
H
J
H
) v theo mt cch ni c bit.Phi tha nhn rng, tnh mm do ti t hp ng vai tr nh
mt yu t lm tng 100 ln Diversity chui nng. Nh vy ti t hp sinh dng c th to ra khong
250 x 10 x 6 x 100 = 1,5 x 10
6
chui nng khc nhau cho mt lp cho. Khi ta tnh thm s Diversity
ca chui nh K (ng sao lng l ) th n c th n mc 7500 x 1,5 x 10
6
= 11 t dng
Immunoglobulin khc nhau ca mi lp c to thnh bi ti t hp sinh dng gia 400 on gen
khc nhau (hnh 9.12)
8. Protein RAG1 v RAG2.
Cc tn hiu ti t hp lm trung gian ni V(D)J (Hnh 9.8) v hnh (9.12) l cn thit v
hng dn cho qu trnh ny. Nhng quan st sau ny chng minh rng tt c cc phn ng ni
V(D)J u c xc tc bi V(D)J Recombinase n c bo tn trong qu trnh tin ho. Thng qua
vic s dng k thut DNA ti t hp, David Baltimore xc nh c mt gen hot ho ti t hp
Hnh 9.12: V tr t hp hnh vng v ng gia
nh gen chui nng dng mm tc ng trung
gian bi ti t hp sinh dng gia cc on V
11
v D (bn tri) v gia D v J
11
(bn phi)
(Recombination activating gene) RAG1 ca ngi v ca chut m ho cho cc protein bao gm 1043
v 1040 gc c ti 90% trnh t phn bit. Protein RAG1 tng t nh mt receptor glucocorticoid, n
bao gm cc gc Cys gn kim loi v v th khng ly g lm ngc nhin, chnh l mt protein gn
DNA.
Tuy nhin, s c mt ca protein RAG1 thc y s ti t hp V(D)J, nhng iu hon
ton cha hiu lc. V th mi dn ti vic pht hin ra mt gen th 2 c bo tn trong qu trnh
tin ho l RAG2, cc sn phm protein ca n s lm tng s ti t hp V(D)J 100 ln cao hn so
vi RGA1, gen ny cnh nhim sc th ca RAG1.
Cn lu rng h thng ti t hp cn i hi s tham gia ca 2 protein cha c r, chng
hn nh cc sn phm ca gen int v xis cho vic ct DNA bacteriophage t nhim sc th tc ch
E. Coli bng ly gii.
9. t bin sinh dng.
t bin sinh dng l mt nguyn nhn xa hn ca tnh a dng khng th. Mc d rt
nhiu Diversity khng th c to ra bi ti t hp sinh dng, nhng cc Immunoglobulin c
lin quan nhiu vi nhng bin i ca t bin sinh dng vi 2 dng.
Dng th nht: Trong khi ni V
H
/D v D/J
H
th mt vi nucleotide c th c thm vo hoc
b loi i trong qu trnh ni ti t hp ny. Cc nucleotide c thm vo ny s to nn ci gi l
vng N, to nn cc n v NDN trn 30bp m ho cho rt nhiu on bin i ca chui nng bao
gm t 0 n 10 gc aminoacid (Hnh 9.11). Baltimore cho rng vng N c to nn thng qua s
tc ng ca Terminal deoxynucleotidyl Transferase, mt polymerase DNA phin c lp c mt
cc t tin t bo B, enzyme ny lm nhim v ni cc chui nng, nhng c th khng thy c cc
th h t bo khi hnh thnh s ni chui nh.
Dng th 2: Nhng vng bin i ca c chui nng v chui nh u c s bin i nhiu
hn, l c s so snh cc trnh t aminoacid vi cc trnh t nucleotide dng mm tng ng
ca chng. Tht vy, tc t bin vng ny l trn 10
-3
thay i base cho mi nucleotide ca mt
th h t bo, tc ny cao hn t nht hng triu ln tc t bin t pht nhng gen khc. T
tin t bo B hoc t bo B r rng l c cc enzyme lm trao i trung gian siu t bin sinh
dng (somatic hypermutation) trong cc on gen bin i ca Immunoglobulin. V th vi tc
ny cc t bo B nh c hot ho lm tng sinh do i lc ca khng th b mt ca chng vi khng
nguyn, siu t bin sinh dng c coi l s tc ng qua nhiu th h chun xc khng th i
vi mt khng nguyn c hiu.
Qu trnh t bin sinh dng lm tng s lng ca cc khng th m con ngi c th to
ra bi ti t hp sinh dng n vi con s 11 t. Con s ny qu tht qu ln, c l l > 10
10
, nhng
thc t c th n ch tng hp mt lng nh cc Immunoglobulin. Nhng bin i sinh dng c
to bi ti t hp v t bin cho php cc c quan ca c th ghi li theo quy lut u tranh sinh
tn ca Darwin, vi tc t bin nhanh i vi cc vi sinh vt gy bnh.
10. S loi tr Allele m bo cho khng th c tnh c hiu cao.
Cc Ig c tng hp bi t bo B, nh chng ta thy n bao gm 2 chui nng v 2 chui
nh tng ng. Tnh tng ng ny cn thit cho chc nng c bit ca h min dch bi v cc
Ig cha 2 dng chui nng hoc 2 dng chui nh th s c t nht 2 v tr gn khng nguyn khc
nhau v v th khng th to c hng ro khng nguyn lin kt cho. Nhng cc t bo B cng
ging nh cc t bo sinh dng khc, n l lng bi, c cha 2 h gen chuyn ho cho chui
nng (mt allele m v mt allele b) v 4 h gen m ha cho cc chui nh (2K v 2). R rng
l cc t bo B c kh nng km hm s biu hin ca tt c cc allele tr mt allele chui nng v
mt allele chui nh, qu trnh ny gi l qu trnh loi tr allele do s c ch ti t hp hu ch
xy ra.
S loi tr allele c chng minh bng thc nghim nh sau: tim mt lng nh Plasmid
c cha cc gen chui K ti t hp vo mt t bo trng chut th tinh. Kt qu l chut chuyn
gen ny km hm s ti t hp ca cc gen chui K.
Nhng kt qu tng t cng thu c vi cc gen chui nng. Mc du c ch loi tr allele
vn cha r nhng c kh nng l cc sn phm protein ca cc s kin ti t hp thnh cng c
ch ton b qu trnh ti t hp tng t sau ny.
11. S chuyn i t dng lin kt mng n dng tit ca mt khng th.
S chuyn i t dng lin kt mng n dng tit ca mt khng th l do s thay i phin m
ca chui nng. M hnh la chn dng ca s pht sinh khng th i hi rng khng th bc l trn
b mt ca cc t bo B cn trinh cng c tnh c hiu khng nguyn ging nh cc khng th c
tit ra bi cc hu th ca t bo B chn. IgM gn mng (mt khng th c tng hp bi cc t bo
B trinh) neo vo mng sinh cht bi mt polypeptide k nc 41 gc to nn cc cui C ca chui
nng (m).
Dng tit ca IgM (khng th u tin c tit ra bi cc t bo B chn), chui nng (s) c 2
on cui C phn bit nhau. Vy cc t bo B thay i s tng hp chui nng ny nh th no ?
Hnh 9.13: S chuyn ho cc gen C i vi protein s thng qua s la chn ni thay i v tr
polyadenylate ho. Trong m mARN (tri) on cui exon C
11
3 (6) chuyn ni s
polyadenylate sau 2 exon chuyn ho on vn chuyn mng (7+8). Cc s mARN (phi) li
polyadenylate ng sau on ui s cn li
Cc gen chui nng ti t hp sinh dng bao gm 8 exon C (Hnh 9.13 ): Mt on L m ho
on dn peptid tn hiu, mt n v VDJ m ho vng V
H
; 4 exon m ho vng C
H
1, vng bn l,
vng C
H
2 v vng C
H
3 v 2 exon m ho chn lc ui vn chuyn mng ca m. Trong vic hnh
thnh m RNA c hiu m, s ng vng ca h loi ra mt on cui exon C
H
3 c hiu ui s
v s phin m y kt thc nh thng l bi poly (A). Trong s hnh thnh s mRNA th s
ng vng li lm h gi li on s v phin m polyadenylate xy ra sau thi im ny v th loi
tr c on vn chuyn mng. Cc t bo B khi c kch thch bi khng nguyn c s chuyn
i nh th no gia s ng vng cui cng v v tr polyadenylate th vn cha r.
12. S chuyn lp Immunoglobulin ca cc t bo B.
Cc t bo B c th chuyn lp Immunoglobulin m chng tng hp. Cc t bo B trinh tng
hp ch yu cc IgM gn mng. Nhng con chu ca cc t bo B li b kch thch tng sinh tng
hp cc lp Ig khc nhau c cc vng bin i ging nhau cng nh cc IgM gc. Cc trnh t
acid nucleic c hiu cho vng bin i ca chui nng v th tr nn gn k vi trnh t c hiu
vng c nh ca cc ca chui nng. Vy c ch ca s chuyn lp l g ? Nhng vng bin i
ca h gen chui nng ngi nh chng ta thy, n bao gm 8 on m ho cc vng c nh
cho cc lp v di lp (Hnh 9.14). S chuyn lp c th xy ra qu trnh thng qua RNA hoc
DNA. Trn thc t, c 2 c ch ny u xy ra. Trong c ch xy ra RNA th khng xc nh
c s kin chuyn i (switching) l thay i kt thc phin m, s polyadenylate hay s ng
vng. Nhng trong bt c trng hp no, kt qu vn l tng hp mRNA chui nng c cc vng
bin i ging nhau, nhng vng c nh th khc nhau. T bo v th c th tng hp lin tc 2
hoc nhiu hn cc lp Ig vi cc v tr gn khng nguyn ging nhau.
Hnh 9.14 :S chuyn lp qua trung gian DNA
C ch chuyn lp vi DNA xy ra thng qua s ti t hp sinh dng gia n v VDJ v
vng C la chn. lm vic , cc on DNA xen gia c loi b, v th c ch ny xy ra
khng thun nghch. V d s chuyn i ti t hp t to IgM ti to IgG (Hnh9.14) th t bo B
mt cc on C, C v C3, v th hu th ca n khng th tng hp c IgM, IgD hoc IgG3,
nhng vn cn tim nng chuyn i tng hp IgG2, IgE v IgA v s ti t hp khng gy phin
toi ti cc on C2, C v C.
Mi on C
H
c s loi tr C do s chuyn i hoc vng S bao gm cc yu t b cu ngn
lp i lp li (C ch c biu hin thmng qua RNA). V th vng S ny c th to nn cc tn hiu
ti t hp s dng trong s chuyn lp.
13. Receptor t bo T
13.1.Receptor ca t bo T vi khng nguyn: TCR.
C 2 dng TCR: TCR1 v TCR2. Khong 95% t bo mu biu l TCR2 v 5% l TCR1.
TCR2 (hay TCR) l mt dimer tp gm 2 chui v ni vi nhau bng lin kt ng
ho tr. Chui l sn phm ca s sp xp li cc gen trn nhim sc th 14; chui l t cc gen
trn nhim sc th 7. Mi chui c mt vng bin i tng t nh Immunoglobulin, mt vng c
nh, mt phn xuyn mng v mt phn nm bn trong nguyn sinh cht (cho nn c xp vo trong
siu h Ig).
Mt trong nhng khc bit ln vi Immunoglobulin l TCR nhn bit khng phi l phn
epitope nm trn khng nguyn nguyn vn m l mt peptide t 8 n 20 axit amin do khng nguyn
b tiu ho m ra v c bc l bi mt "t bo trnh din khng nguyn" (nh i thc bo, lympho
B) trn mt phn t HLA lp II i vi t bo CD4+ hay HLA lp I i vi t bo CD8+.
TCR2 lin kt vi 4 chui polypeptide , , , ca CD3, cho php chuyn t tn hiu khng
nguyn vo bn trong t bo T.
Cui cng l s kt hp ca cc phn t, mt bn l CD2 v LFA1 ca t bo lympho v bn
kia l LFA3 v ICAM1 ca t bo i ng lm tng cng thm s bm dnh gia t bo lympho T
ph tr v t bo trnh din khng nguyn hay gia t bo T c vi t bo ch.
13.2. Cc receptor khc ca t bo T.
Receptor vi on Fc (FcR) ca Ig. Nhng Receptor ny khng ch c trn t bo T. Cc t
bo lympho T v B cng nh nhng t bo khc trong mu, hay cc m, u c th biu l Receptor
vi on Fc ca cc lp hay di lp Ig khc nhau. C th khng thy r cc receptor y trong vic
hnh thnh hoa hng EA (hng cu gn khng th) hay bng khng th n dng. S c mt ca chng
tng ng vi cc chc nng hiu ng hay iu ho.
TCR1 hay TCR : Cc lympho cha chn mang Receptor ny nn chng nhn bit c
khng nguyn m khng b hn ch bi MHC (cho nn c th l mt nguyn nhn gy bnh t min ).
Hnh 9.15. Cc thnh vin ca siu h Ig (a) Receptor t bo T, (b) IgM gn mng, (c)
Protein MHC lp I v (d) protein MHC lp II.
Receptor vi interlcukin 2 (IL-2) hay CD25. Receptor vi IL-2 tham gia vo s pht trin t
bo T v trong p ng min dch t bo khi c kch thch (n xut hin khi t bo c hot ho, trn
t bo lympho T cm ng va c CD25 va tit IL-2 nn c hin tng t kch thch (autocrin) lm
khuych i phn ng.
Receptor b th (C). C 2 loi: CD35 hay CR1 v CD21 hay CR2.
Receptor vi IL-1, IL-4, IFN , hormone, lectin.
Nhng tin b gn y cho thy trn t bo lympho ngoi cc Receptor vi cytokin cn
c c Receptor vi hormone v cht dn truyn thn kinh nh ACTH, endorphin... nn mi c
khi nim m rng h thn kinh hormone - min dch (hnh 9 15).
14. Phc hp ho hp t chc chnh.
Cc protein gn trn mng c m ho bi phc ho hp t chc chnh (major
Histocompatibility complex - MHC) nh chng ta thy, n l cc maker trnh din khng nguyn
(Protein MHC lp I) v marker ca cc t bo min dch (Protein MHC lp II). Di y chng ta s
xt v cu trc cng nh bn cht di truyn ca cc protein cn thit ny.
14.1. Protein MHC c tnh a dng cao.
MHC c nghin cu m rng c trn ngi cng nh trn chut. ngi, protein MHC
lp I c m ho bi 3 locus ng nht di truyn nhng tch bit l HLA-A; HLA-B v HLA-C
(Hnh 9,16). (HLA = human - leucocyte - assciate antigen, v nhng protein ny ln u tin c tm
thy bch cu Leucocyte). V vy, mi c th tng hp trn 6 protein MHC lp I khc nhau. ngi
cng c 3 protein MHC lp II m cc chui v ca n c m ho bi cc gen DP, DP, DQ,
DQ, DQ v DR (Hnh9.16). Gen MHC ca chut locus H-2 cng c sp xp tng t nh
trn.
Hnh 9.16:Bn di truyn ca MHC trn ngi m ho protein HLA . Gen lp III m
ho mt s protein ca b th
Hin tng ni bt nht ca cc gen MHC lp I v II l tnh a dng cao gia cc c th. Thc
cht chng l cc gen a dng nht bit ng vt c xng sng bc cao. V d ngi c 23
allele A, 49 allele B v 12 allele C c cc c tnh ring c pht hin. Cng tng t nh vy, c
> 50 allele gen MHC lp I ca chut. Hai c th khng c quan h vi nhau th khng ging nhau
nhiu n mc c cng mt b gen MHC.
14.2. Protein MHC lp I.
Cc m c th c cy t mt b phn ca c th ny sang c th khc hoc gia cc c th
ging nhau v mt di truyn ( sinh i). Nhng ngay c khi cc m c cy vo gia cc c th c
quan h gn gi th cc mnh ghp cng b hu hoi bi h thng min dch ca c th tip nhn.
(Hin tng ny l tr ngi chnh i vi vic ghp cc c quan nh tim v thn). Nhng nghin cu
v s loi tr mnh ghp nh th gn 50 nm tri qua, do vic pht hin ra protein MHC lp I
c hiu l khng nguyn ghp (Transplantation antigen).
Protein MHC lp I l cc glycoproteit vn chuyn mng 44 - KD c bc l trn b mt hu
ht cc t bo c nhn ca ng vt c xng sng. Cc trnh t aminoacid ca nhng protein ny
c cun li trong 5 vng t cui C n cui N, mt vng t bo cht 30 gc v mt on vn
chuyn mng 40 gc, 3 vng bn ngoi k hiu
3
,
2
v
1
(Hnh 9.15 c) 90 gc. Cc protein
MHC lp I c lin kt vi nhau bi lin kt khng ng ho tr vi t l 1:1 vi
2
- microglobulin
(
2
m; Hnh9.15, c); l mt protein 12 - KD. Cu trc tia X ca phn nm ngoi t bo ca protein
MHC lp I, HLA-A
2
c lm sng t bi Don Wiley v Jack Strominger, cc ng ch r rng vng
3
cng nh
2
- microglobulin u tng ng vi cc Immunoglobulin, tc l tha nhn
Immunoglobulin gp np. Mt cch r rng l tt c cc protein ny cng vi cc receptor t bo T
u c quan h tin ho v to nn siu h gen (mt b gen c quan h tin ho vi cc chc nng bin
i).
Cc vng
1
v
2
tng ng ny ca HLA-A
2
to nn mt tm i song song 8 dy n c
quan h vi nhau xp song song vi mng t bo v i dc bn sn bi 2 son . Do c rnh su
hoc khe va kch thc v hnh dng son nn n c th gn vi mt polypeptide c 8 - 10 gc to
nn v tr gn ca on khng nguyn c t bo x l, n gn vi chnh protein MHC lp I ny
v c nhn bit bi Receptor t bo T.
Tht vy, HLA-A
2
cha mt lin kt "khng nguyn" cha r trong rnh ( c tinh khit
v kt tinh li) vi protein MHC lp I (c tng hp trong mt dng t bo nui cy ca ngi ). Tuy
nhin, nhng gc aminoacid l khc nhau gia HLA-A
2
v 2 protein MHC lp I khc m cu trc tia
X c xc nh (HLA - Aw 68 v HLA - B27) tp trung trong v bao quanh khe gn khng
nguyn.
Cu trc tia X ca protein MHC lp I ca ngi cng nh ca chut u to phc vi cc
peptide ni sinh hoc vi cc peptide octa v nona ngoi sinh c hiu chng t rng nhng
protein ny gn vi peptide thn cn (Cognate) ca chng v trnh din ti Receptor t bo T. Cc
peptide ny gn vi cc protein MHC lp I hu ht qua lin kt hydrogen khung peptide, cc peptide
c s son li v ni rng cu trc ging nh son polyprolin II. V th cc mch bn peptide k tip
s nh ra theo hng i nghch, n hi ging chui bn ca mt dy trong np gp . Trong phc
hp protein H - 2K
b
ca chut vi mt nonapeptide Virus chng hn th chui bn ca cc gc P
2
, P
3
,
P
6
v P
9
( y P
n
l ch th t gc ca peptide) mt hng vo trong tip xc vi protein trong
nhng ci ti gn vi chng).
Nhng chui bn cn li t nht c mt phn tip xc vi dung mi v co th tng tc vi
Receptor t bo T. Thm vo na, cc cui N v cui C ca cc peptide gn vo su v bo v cc
ti ny cui khe gn Protein MHC thng qua lin kt hydrogen tip xc vi cc gc c
bo v,v vy chng ta bit c hng I ca peptide.Nh vy octapeptide ny gn vi H-2Kb l
cn thit duy tr tip xc tng t nh vi nonappeptide bi v gc P
5
ca nonapeptide c
iu chnh thng qua vic hnh thnh mt chli trung tm (tc l cc gc t P
6
ti P
9
trong
nonamer tng ng vi P
5
ti P
8
trong octamer).
Kch thc v v tr ca cc amino acid ti c cha cc chui bn ht gi chng t rng bt
k mt protein lp I c bit no cng ch c th la chn mt cch gii hn cc peptide. V d trong
phc hp ca HLA - B27 vi cc peptide ni sinh, chui bn P
2
gn vo mt ti k nc kt thc
gn Cys 67 v Glu 45 tch in m. iu ny chng t rng v tr ny gn u tin mt chui di, tch
in dng. Trong thc t, tt c 11 peptide c HLA - B27 u cha Arg P
2
. S phn bit cc
chui bn ht gi khc P
3
, P
7
v P
9
mc du khng gii hn nh P
2
, n c hoc t hoc nhiu bn
cht ti, cn trong khi cc chui bn u dung mi th c s phn bit rng hn.
Nhng peptide cc protein HMC lp I khc cng th hin cc ho tit trnh t c hiu allele
tch bit. c bit, mi ho tit trnh t c cha 2 v tr neo, n c th ch c mt hoc nhiu gc c
chui bn quan h gn gi. V tr neo ny thay i vi tng protein MHC.
Trong c gng lm r vai tr ca cc gc c HLA-A
2
, ngi ta thy c s tng tc vi
u cui N v u cui C ca peptide m HLA-A
2
gn. Stromiger pht hin hiu ng t bin ca
nhng gc ny trn phc hp peptide HLA-A
2
l kh nng hot ho ca cc t bo T Killer. C 2 gc
Tyr u gn vi cc cui N ca nonapeptide influenza Virus c t bin bng Phe. iu dn
ti 2 vn ln: Mt l kh nng ca cc t bo T Killer l lm tan cc t bo c HLA - A
2
t bin v
hai l cc HLA - A
2
t bin ny u phi by mt nonapeptide hoc influenza Virus tip xc. R
rng l lin kt Hydrogen m cc chui bn Tyr to vi cc nhm amin cui N v c th c
nonapeptide lin kt HLA - A
2
chuyn bit cho hot ho T Killer. Tuy nhin, s t bin cc gc Tyr
v Phe hnh thnh lin kt Hydrogen vi nhm Cachoxyl cui C ca nonapeptide, nhng Phe v
Val th khng hot ho c T Killer.
14.3. Protein MHC lp II.
Baruj Benacerraf l ngi pht hin ra protein MHC lp II, ng quan st thy rng cc p ng
min dch no thng qua mt trung gian l sn phm gen, ch khng phi l khng th. V d nh
khi chut bch c tim chng vi mt khng nguyn n nh polylysine, c mt s c th p ng
rt mnh i vi khng nguyn ny trong khi cc c th khc li khng p ng. p ng min
dch vi mt khng nguyn cho l mt c trng di truyn ni bt. Mt s nh ci gi l cc gen
p ng min dch (Ir) r rng l iu khin c th p ng vi tt c cc khng nguyn n.
Mt c th lun lun c th p ng min dch chng li cc khng nguyn xm nhp mt cch
t nhin. Bn gen Ir

trn MHC v th by gi c hiu l cc gen MHC lp II. Chng m ho cho
2 subunit (di n v) ca mt glycoproteit vn chuyn mng heterodimer c chui - 33 - KD v
chui - 28 - KD. Mi chui c 2 vng (Hnh 9.15d). Cc trnh t amino acid ca cc subunit ny ch
ra rng cc vng cui C ca
2
v
2
l cc thnh vin ca siu gia nh gen Immonoglobulin. Tuy
nhin, cc vng
1
v
1
c th sp thng hng trn mt cu trc bit ca cc vng
1
v
2
ca
protein MHC lp I. iu ny chng t rng protein MHC lp I v lp II c cu trc cng nh chc
nng tng t. D on ny c khng nh bi cu trc tia X ca phn nm ngoi t bo ca
protein MHC lp II, HLA - DR1. Cc phc hp ca n vi hn hp cc peptide ni sinh v mt on
gm 13 gc ca protein hemagglutinin ca Virus influenza (HA) c xc nh bi Strominger v
Wiley. Tuy nhin, v tr gn peptide ca HLA - DR1 l mt vng m cui, trong khi protein
MHC lp I li l nhng rnh ko di nhng cui th ng li. iu ny gii thch ti sao protein
MHC gn peptide vi chiu di tu tin, trong khi protein MHC lp I gn ko di l ch yu nhng
li c cc nonapeptide phng ra ngoi. Nh vy, cu trc tia X ca HLA - DR1 trong phc vi HA 13
gc chng t rng peptide ny rui ra c 2 ui ca ng rnh gn ca n.
Tuy vy, protein MHC lp I v lp II u l cc dimer , HLA - DR1 c kt tinh nh mt
Dimer trong tt c 4 mt cui C u cng 1 hng v b mt ca khe gn peptide u hng
i din. y l mt cch trong cc dimer protein MHC lp II biu l c s kt hp trn mng
b mt t bo.V ligand cm ng s dimer ho ca cc Receptor b mt t bo l c ch dn truyn cc
tn hiu nn c th l s dimer ho ca Receptor t bo T trhn thuc c lm theo kiu hot ho t
bo T. iu ny s gii thch ti sao cc receptor t bo T c hot ho bng cch lin kt cho vi
khng th hai ho tr (divalent) ch khng phi bng on Fab mt ho tr (monovalent) tng ng.
14.4. Tnh a dng ca MHC.
Tnh a dng ca MHC c chc nng bo v quan trng. Hu ht cc gc c tnh a dng
trong protein MHC u c tp hp li thnh cc cm, nh chng ta thy rnh gn khng nguyn
phi nh th no mi bch cu a nhn gn vi mt on khng nguyn cho vi mt i lc
c trng (ngi ta xc nh c rng bt k mt MHC lp I bch cu a nhn no cng c th
gn < 1 % octapeptide v nonapeptide m n chm trn). Nhng quan st m t trn v s thay
i p ng min dch vi cc gen (Ir) MHC lp II v th c xc nh rng mt s protein MHC lp
II bch cu a nhn tc dng yu hn so vi cc lp khc trong vic kt hp vi mt epitope cho.
Tht vy, nhng nghin cu dch t min dch ch r rng nhng bch cu a nhn nhy cm tng
ln hoc gim xung i vi mt bnh nhim khun hoc bnh t min. V d nh 95% c th b i
ng ph thuc insulin mang t nht mt allele DR2 hoc DR3 ca gen DR, cn ngi bnh thng
ch chim 50%. Nhng trong bnh Celiac (bnh ri lon nng ng rut do n gluten la m) l 100%
bi allele DQw2 ca gen DQ. Ngc li, mt nghin cu v s phn b ca cc allele MHC tr em
Chu Phi b st rt nghim trng c so snh vi nhng tr em b nhim bnh nhng khng chu tc
ng ln (ch c mt b phn nh tr nhim k sinh trng st rt l b e do tnh mng) ch r rng
HLA-Bw53 ca protein MHC lp I v DRB1 1302 - DQB1 0501 ca protein MHC lp II l kt hp
mt cch c lp chng li bnh st rt kch lit. Nhng Allele ny kh ph bin dn Chu Phi (~
1% tr di 5 tui cht v st rt). Nhng allele MHC ny dng chng li bnh st rt hn l chng
li hnh nh t bo hnh li lim.
Chc nng ca protein MHC bch cu ht l g ? Dng nh l n khng ging nh tin ho
m ch phng cc m ghp v cc Receptor t bo T ch nhn dng c khng nguyn khi
chng c trnh din cng vi protein MHC. Nu bt k mt mu n no c mt b ging nhau v
protein MHC. Nu mt pathogen m cc epitope ca n tng tc yu vi cc protein MHC ny th s
gch i cc mu . Gen MHCbch cu ht c l l phng pathogen v qua tin ho m c kh
nng ny. V th s la chn t nhin s dn ti vic duy tr s thay i ln protein MHC trong mt
qun th..
15. H thng b th.
15.1. Khi nim v vai tr ca b th.
Cc khng th vi tt c s phc tp ca n ch phc v cho vic phn bit khng nguyn l.
Cn mt h thng sinh hc khc lm bt hot v ngn tr s xm nhp t bn ngoi, l h
thng b th.
B th l h thng enzyme k hiu t C1 n C9, hot ng c tnh cht lin hon, dy truyn
vi vai tr y mnh qu trnh phn ng min dch. S dung gii vi khun, t bo hng cu ch din ra
khi c mt ca b th, n hot ho phn ng ngng kt, kt ta v thc bo. Chc nng ca b th, th
hin ch l n gn vi phc hp KN-KT p ng vi nhng tc dng ca KT. B th hot ng
theo 3 cch:
Git cc t bo l bng cch gn v lm tan mng t bo, qu trnh c hiu l c nh b
th ( complement fixation).
Kch thch s thc bo cc vt l, qu trnh ny c tn l s opsonin ho.
To ra phn ng vim cc b.
H thng b th bao gm ~ 20 protein huyt tng (bng 9.2) n tng tc trong 2 b phn ng
c lin quan vi nhau (Hnh 9.17): Con ng c in ph thuc khng th (antibody - dependent
Classical pathway) v con ng khc khng ph thuc khng th (antibody - independent
alteRNAtive pathway). C hai con ng u gm nhiu phn ng hot ho trnh t ca mt sery cc
protease serine, rt ging qu trnh ng mu. H thng b th c tn gi rt khc thng. Hu ht cc
tn protein b th u c ch "C" v theo sau l tn s cc thnh phn, nu protein li c cc subunit
hoc cc on protein ln th li c ch t di. Cc protease hot ho c ch nh bng du gch
trn cc thnh phn ring bit. V d: C4b l protease c hot ho bi s proteolysis C4.
15.2. Hot ho b th theo con ng c in.
Trong con ng c in, cc protein b th to nn 3 phc hp gn mng hot ho trnh t
(hnh 9.17,).
n v nhn bit, gn vi phc hp khng nguyn - khng th gn trn b mt t bo.
n v hot ho, khuych i s nhn bit thng qua thc proteolytic.
Phc hp tn cng mng (membrane attack complex - MAC) phc hp ny chch vo mng
sinh cht ca cc t bo v gy nn s ly gii ri cht ca t bo.
Hnh 9.17. S cc con ng hot ho b th. Cc mi tn ch hot ho proteolytic.
Proteolytic hot ho c ch bng mt gch trn ch s ca hp phn.
15.2.1. n v nhn bit.
Con ng c in c khi u khi C1, mt n v nhn bit gn c hiu vi t hp khng
nguyn - khng th trn b mt t bo. C1 c mng sinh cht, c coi nh l phc hp gn lng lo
ca C1q, C1r v C1s. C1q l protein ch yu nht, n gm 18 chui polypeptide A
6
,B
6
,C
6
trong cc
gc cui N 80 ca mi chui c s lp li cc trnh t Gly - X - Y mang c tnh Collagen. y X
thng l Pro v Y thng l 4 - Hydroxyproline hoc 5 Hydroxylysine. C1q v th l 1 b gm 6
vng son ging Collagen m cui mi son l mt vng cui C hnh cu gn vi nhau cng tng t
1 b gm 6 hoa tulip (Hnh 9.18). Nhng vng hnh cu ny gn khng th - khng nguyn thng qua
s nhn din ca vng Fc ca IgM v mt vi di lp ca IgG (mc d Fc phc khng nguyn -
khng th khc vi cu trc dng khng th t do nh th no th vn cha r). Tuy nhin, C1 ch
c hot ho nu 2 u C1q ca n c gn lin tc vi khng th, qu trnh ny i hi s tham
gia ca t nht 2 phn t IgG, nhng vi IgM th n c hiu lc xa hn. Ch mt thay i v c cht
bao gm c Lipopolysaccharid vi khun v mng Virus cng c th hot ho c C1. Phn cn li
ca C1 l C1r v C1s l nhng zymogen protien serine ng dng cng ging nh hu ht cc
zymogen ng mu, chng u b hot ho do vic ct proteolytic to nn 2 chui lin kt disulfide.
Bng 9.2: Cc thnh phn Protein ca h thng b th.
Protein Cu trc di n
v
Khi lng phn
t
n v nhn bit (C1)
Clq A
6
B
6
C
6
460
Clr
2
157
Cls
2
150
n v hot ha
C2 Monomer 81
C3 174
C4 187
n vi tn cng mng
C5 190
C6 Monomer 102
C7 Monomer 91
C8 142
C9 Monomer 61
Con ng khc

Factor B Monomer 83
Factor D
Monomer 24
Properdin (P)
4
224
Protein iu ha
Factor H Monomer 137
Factor I

63
Protein gn C4b
7

570
Cht c ch C I
Monomer 53
Protein S Monomer 52
Vic gn phc hp khng th - khng nguyn s kch thch C1q gn cht hn vo 2 subunit ca
C1r v C1s, l mt qu trnh ph thuc Ca
2+
, kt qu l lm t hot ho C1r thng qua vic ct lin
kt Arg - Ile. C1r khi n lt mnh li ct c hiu C1s lin kt Arg - Ile to C1s .

Hnh 9.18: Cu trc ca protein b th C1q
15.2.2. n v hot ho.
n v hot ho bao gm cc thnh phn dn xut t C2, C3, C4 bc khi u hnh thnh
n v hot ho. C1s ct C4 lin kt Arg - Ile to ra cc mnh C4b gn ng ho tr vi mng t bo
trong vng ln cn ca n v nhn bit. C4b gn mng kt hp vi C1s , ct c hiu C2. C2a gn vi
C4b to nn C4 2 a a , , l mt protease c tn l C3 convertase n ct C3 thnh C3a v C3b. Cui
cng C3b gn vi C3 Convertase to nn n v hot ho C4 2 3 b a b , , , chnh l C5 Convertase
m chc nng ca n l hot ho C5 proteolytic bng cch ct lin kt Arg- Leu.
C C4 v C3 u i vo nhm Thioester phn ng cao khi n c th lin kt ng ho tr cc
protien ny vi mng t bo. Trong C3, Thioester bao gm mt Cys thiol v mt nhm Cacboxyl ca
Glu to nn mt vng ln cc ui Gly - Cys - Glu - Gla - Asn.
Khi ct C3, sn phm C3b phi tri qua s sp xp li cu trc bc l nhm Thioester ca n.
Sau Thioester phi ng vi nhm OH hoc nhm amin gn b mt t bo to cc amide tng
ng hoc to lin kt ester vi mt nhm sulfhyhydrin. Chc nng ca qu trnh ny s bn lun sau.
C4 c hot ho cng tng t nh vy.
S hot ho C3, C4 v C5 cng to ra nhng chc nng khc cho h min dch. C3b, C4b
to nn s opsonine, l nhng c cht kch thch s thc bo (phagocytosis) (s opsonine ho),
trong C3a, C4a v C5a (mt sn phm ca phn ng Convertase C5 to nn c cht phn v
(anaphylatoxin), cc c cht kch thch phn ng vim cc b v co tht c trn.
15.2.3. Phc hp tn cng mng.
Hnh 9.19. Phc hp tn cng mng (MAC) l mt cu trc hnh ng to nn mt l xuyn
mng mng sinh cht ca t bo ch.
C5b, mt sn phm kh ca phn ng C5 convertase, biu l khng c hot tnh proteolytic.
Tuy nhin, n gn trnh t C6 v C7 to phc i vo lin tc trong mng t bo. Phc hp C5,6,7
sau gn vi C8 v theo sau l khong 18 phn t C9 to nn MAC. Tip theo,phn t C9
polymer ho to mt cu trc gn cht vo mng c hnh ng phc C5b,6,7,8 gn tht cht vo
(Hnh 9.19). T bo b ly gii l do MAC to mt knh cha ng knh 30-100, knh ny m
thng mng, lm tng tnh thm ca n. C 2 c ch ny cho php ch cc phn t nh ca t bo mi
trao i c vi mi trng xung quanh. V vy nc c thm thu vo gy nn s trng phng
v lm v t bo. D nhin ch c cc MAC hiu lc mi git c t bo.
15.3. Hot ho theo con ng cnh c lp khng th.
Con ng cnh ca c nh b th (Hnh 9.17) s dng nhiu thnh phn ging nh con ng
c in v cng to thnh C5 Convertase gn MAC. Hai con ng ny khc nhau ch l con
ng cnh l c lp - khng th chng li s xm nhp ca vi sinh vt. V th ngi ta ngh rng
chc nng ca con ng cnh l bo v, chng li s xm nhp ca vi sinh vt trc khi c p ng
min dch chng li chng. (con ng c in cng c chc nng nh vy). Khi khng th c tng
hp th con ng cnh m nhn mt vai tr th hai c lin quan ti con ng c in.
Con ng cnh thng c hot ng mc thp to ra mt cch lin tc mt lng nh
C3b, mt phn t ging nh c to ra bi C3 convertase ca con ng c in. Tuy nhin, trong
con ng cnh th C3b gn vi factor B ca protein sinh cht trong mt phn ng ph thuc Mg
2+
.
Phc hp to thnh C3b, B ch c hiu nh l c cht cho Protease serine sinh cht hot ho, yu t
D ct subunit B ca C3b, B to C3b, Bb. Phc hp C3b, Bb tng ng vi C3 convertase,
nhng phn bit vi con ng c in. N ct C3 thnh C3b tham gia vo vic hnh thnh nhiu
hn C3 convertase trong mt qu trnh khuych i vng. Thm vo na, C3b cng gn vo C3
convertase to (C3b)
2
Bb, mt C5 convertase phn bit vi con ng c in nhng n cng c
tnh xc tc tng t trong vic hnh thnh MAC.
Vy ci g l ngun gc ca C3b m n li khi u con ng cnh? D nhin, n c th c
to ra bi con ng c in, nhng trong trng hp con ng cnh th n li tc ng nh mt c
ch khuych i khng th - cm ng hot ho b th (antibody - induced complement activation).
Tuy nhin, nu thiu qu trnh ny th n vn c phn ng nhng khng bc l c lin kt Thioester
ca C3 m m phi tri qua s thu phn lin tc to mt protein ging nh C3b ; C3i gn vi yu
t B v qua trung gian D - hot ho xc tc. V C3 convertase s to ta C3b xc thc.
Con ng cnh hng vo cc vi sinh vt xm nhp nh th no? Khi nng C3b trong dung
dch b gii hn bi mt protein huyt tng c tn l factor I th n cng vi mt protein th 2 l
factor H s to nn mt phc (I - H) n phn gii proteolytic C3b trong dung dch. Khi C3b lin kt
ng ho tr vi b mt nhng tc phn gii b gim rt nhiu. Tuy nhin, phc C3 convertase gn
trn b mt s c n nh bng cch gn vi mt protein huyt tng l properdin (P), n bo v
cho C3b khi b phn gii qua trung gian I, H cng nh lm chm s phn ly ca Bb t C3
convertase. Cui cng, C3b lin kt ng ho tr nhanh hn vi b mt phn gii vi tc chm
hn. Cc c cht m C3b gn mt cch c hiu lc l cc cht hot ho theo con ng cnh. Nhng
iu ny i n mt kt lun rng cc polymer ca cc ngun gc vi sinh vt nh lipopolysaccharide
ca vi khun gram m hay cc acid teichoic vch t bo ca cc vi khun gram dng, nm, vi khun
v cc t bo nhim Virus... u c hiu l cc ni c t (endotoxin). V th con ng cnh
m nhim vic chng li mt cch c hiu qu cc vi sinh vt xm nhp. Nh vy, mt c th c s
thiu ht di truyn v cc thnh phn b th no th hay nhy cm vi s nhim trng.
15.4. S iu ho h thng b th.
H thng b th c iu ho mt cch nghim ngt. N c kim sot mt cch cht ch.
Mt khc, h thng b th cng c th ph hi c cc t bo ca tc ch, chng hn trong cc bnh t
min. H thng b th c iu ho bng cch lm bt hot cc thnh phn hot ho ca n. C 3
cch thc hin:
1. Cc thnh phn ca b th b bt hot thng qua s suy gim lin tc ca n. V d nh cc
Thioester phn ng cao ca cc C3b v C4b hot ho mi sinh s phn ng vi nc vi thi gian bn
sng (half life) ch 60 s (micro giy). V th nhng protein ny b mt con ng c in tr phi
chng gn vo mng ln cn n v nhn bit ang hot ho. iu c ngha l, mng ca cc vi
sinh vt xm nhp lm hot ho chng (hn l ca cc t bo tc ch). Cng tng t nh vy, i
vi C3 convertase, C4 2 b a ca con ng c in c hot ho rt nhanh, nhng C2a d b phn
gii do mt hot tnh enzyme.
2. Cc thnh phn b th b bt hot thng qua s phn gii ca cc protease c hiu ca
chng. Chng hn protein gn C4b to phc vi factor I lm bt hot proteolytic C4b, n rt ging
phc IH phn gii C3b. R rng l protein C4b v yu t H tc ng nh mt Cofactor hng vo
factor I i vi C4b v C3b. T quan im ny ta thy protein gn C4b hn ch s hot ho C3
convertase (4b, 2a) v C5 convertase (C4b, 2a, 3b) theo con ng c in. Trong khi nh chng ta
thy factor H thc hin nh vy i vi protease c cha C3b trong c 2 con ng c in v con
ng cnh.
3. Cc thnh phn ca b th c lm bt hot thng qua vic kt hp vi cc protein gn c
hiu. V d nh C1 inhibitor gn cht vo C1r v C1s to nn mt phc hp, v th lm bt hot
n v nhn bit ny.
Cng tng t nh vy, protein S tn cng vo MAC gn trong t bo cht ngn nga cc tn
cng sau ny vo mng t bo. Nhng s tn cng nh th cui cng lm hn ch v tr hot ho b
th.
S iu ho h thng b th v th thu tm c cc vt xm nhp l v lm gim bt s tn
thng ca cc t bo tc ch.
16. Vaccine ca hin ti v tng li
K nguyn gen hc s gip cho s pht trin ca vaccine mi tng theo s m. Vo nhng nm
70 ca th k 20,vic pht hin trt t gen l iu khng th. Nhng vo nhng nm 80 iu ny
tr thnh hin thc. Hin ti ngi ta bit ton b kiu gen ca vi sinh vt cha khong 3 triu i
base nit. Bng d dng thut ton v my vi tnh, ch trong vi gi ngi ta c th chn lc c ton
b gen thch hp cho vaccine d tuyn.
Mt vn khc c t ra l ng s dng vaccine. Ph bin v kinh in l tim. Nhng s
dng qua ng nim mc ang thu ht nhiu nghin cu vi hy vng thay ng tim, v n trnh
gy au n cho ngi dng, to c min dch v min dch ti ch. Vi nhng tin b ca khoa
hc k thut v yu cu phng bnh, cha bnh, nhiu vaccine mi s ln lt ra i bao gm vaccine
chng nhim trng v khng nhim trng.
t c tnh an ton, hiu qu v kinh t cc nghin cu v vaccine hng ti cc sn
phm:
Vaccine tinh ch: Vaccine khng cn tp cht, ch c khng nguyn hoc quyt nh khng
nguyn.
Vaccine lin kt (Conugate): Polysaccharide lin kt vi protein c phn t lng cao tip
cn d dng vi t bo T.
Vaccine ti t hp DNA: Gen m ho khng nguyn c chuyn np vo genome ca t bo
nm men, t bo vi khun hoc t bo ng vt thch hp to ra nhiu khng nguyn tinh khit nh
phng thc nhn bn. Qu trnh chuyn np gen m ho khng nguyn c thc hin qua yu t
trung gian l Plasmide.
Vaccine DNA trn: Loi vaccine ny c gii m in Vivo v to nn p ng min dch. Tim
vaccine trn l bin php tt x l khng nguyn bn trong c th. iu ny gn vi nhim trng t
nhin hn so vi tim vaccine cha khng nguyn gn vi c cht. Mt u im na l khng th m
truyn sang con khng nh hng g ti p ng min dch.
Vaccine DNA trn to khng th khng cao ngay t u. Nhng nu tim nhc li vi khng
nguyn tinh khit th nng khng th s rt cao v ko di. Vn cn li l tnh an ton ca
vaccine DNA trn.
Vaccine ghp: y l kt qu ca s kt hp k thut ti t hp v k thut di truyn. Chng vi
sinh vt dng lm vaccine c cy ghp gen m ho khng nguyn ly t vi sinh vt gy bnh. Vi
sinh vt c cy ghp l vi sinh vt Vector. Vaccine lai ghp mt lc kch thch c th to ra hai p
ng min dch: p ng bo v i vi vi sinh vt gy bnh v p ng vi vi sinh vt vector. Nu vi
sinh vt vector c chn t danh mc cc vi sinh vt hin c th nh vy ngi ta c dng vaccine
c kh nng chng li hai bnh.
Vaccine ho tng hp: Vaccine peptide l mt v d ca vaccine ho tng hp. Bng phng
php ho hc ngi ta c th to ra chui polypeptide vi trnh t axit amin theo mun, trn c
epitope bo v. Peptide ny c th lin kt vi mt protein ti tng tnh ph thuc t bo T.
To chng vi sinh vt d tuyn lm vaccine: Bng k thut di truyn, ngi ta c th loi b
mt gen m ho tnh trng bt li no v ghp mt gen c li vo mt loi vi sinh vt d tuyn lm
vaccine.
Trong thc t, mt s vi sinh vt d tuyn l vaccine c to ra trong qu trnh nghin cu
vaccine t, thng hn, l. Chng hn nh vi khun Salmonella gy bnh thng hn b lm t
bin gen GalE hoc gen Aro tr thnh chng khng c lm vaccine thng hn sng loi ung. Vi
khun ny khng gy bnh, c kh nng xm nhp nim mc rut nn kch thch p ng min dch
mc cao.
Vaccine thc vt chuyn gen: Thc phm cha gen khng nguyn, khi n thc phm coi nh
s dng vaccine.
Cht b tr Vaccine: Cht b tr l tng c tnh an ton v lm tng hiu lc ca vaccine v
cc tnh cht khc.
Phng php s dng vaccine: Vaccine tip xc vi nim mc qua ng tiu ho, h hp c
th thay th ng tim. S dng vaccine khng tim ang l hng ng c ch .
YU CU CN NM
CHNG IX: MIN DCH HC
Khi nim v min dch. H thng min dch t bo. H thng min dch dch
th. Cu trc v chc nng ca cc loi khng th. Khng th n dng. H thng b
th. vaccin.
Cu 1: Th no l min dch t bo? Vai tr ca cc lymphocyte?
Cu 2: Th no l min dch dch th. Cu trc v chc nng ca cc loi khng th.
Cu 3: Cho bit h thng b th. Qu trnh hot ho b th?
Chng X
S VN CHUYN CC CHT QUA MNG
1. Nhng nt i cng v mng t bo.
Trc y phn ln cc nh sinh hc cha c khi nim v mng. C kin cho rng gia
mi trng ngoi v nguyn sinh cht, ch tn ti mt b mt tip xc, ni tp trung cc cht khc
nhau t mi trng ngoi hoc t nguyn sinh cht ti. Tri qua mt thi gian di, nh s pht trin
ca knh hin vi in t ngi ta mi tha nhn s tn ti ca mng v cng cn phi nhiu nm
ngi ta mi bit c chc nng ca mng.
Ngy nay, chng ta hiu rng t mng sinh hc (biomembrane) dng ch lp cu trc
bao bc bn ngoi cc t bo sinh vt cng nh cc c quan bn trong t bo nh nhn, ty th, lc
lp, lysosome, li ni cht, b my Golgi Chnh v s phn chia khu vc nh vy nn cc t
bo c nhn thc hin c hng lot qu trnh ho hc rt a dng v c s iu tit cht ch
chng hn nh trao i cht, thc bo, tiu ho, tng hp protein, sinh nng lng v.v.. Trong qu
trnh tin ho ca sinh vt, vic xut hin cc loi mng sinh hc l mt bc tin v cht ht sc
quan trng. Mng sinh hc vi thnh phn nn tng l lipid gip ngn cch mi trng trong v
ngoi t bo.
Tuy nhin s ngn cch ny khng lm c lp mi cu trc t bo, cng nh t bo vi mi
trng xung quanh. Tri li, s giao lu trao i vn c thc hin theo hng thun li cho vic
duy tr v pht trin s sng ca t bo. V qua cu trc mng m t bo tip nhn mt cch chn
lc cc cht dinh dng cng nh nhng thng tin cn thit t mi trng xung quanh v a ra
ngoi t bo nhng cht thi loi. Mng khng cn c quan nim nh mt b phn tnh ti ca
t bo, ngc li, n lun c i mi (qu trnh thc bo), nhiu qu trnh c bn, nn tng ca
s sng t bo c thc hin mng (s vn chuyn in t v proton trong qu trnh
phosphoryl ho oxi ho to ATP, qu trnh quang hp h thng mng Tilakoid ca lc lp, s
dn truyn thn kinh v.v..). V th mun hiu r cc qu trnh trn, iu cn thit l phi am hiu
k v cu to mng sinh hc.
2. Thnh phn ho hc ca mng t bo
2.1 Lp kp Lipid ca mng t bo.
Cu trc c bn mng t bo l mt lp kp Lipid, l mt l Lipid rt mng, b dy ch c
2 phn t, lp mng ny lin tc bao quanh t bo. Thnh phn ho hc ca lp Lipid bao gm
nhm glycero phospholipid v nhm Sphingolipid. Ngoi ra cn c mt lng ng k l
cholesterol v dn xut ca n. iu ng lu l cc hp cht Lipid u khng tan trong nc, v
vy chng c kh nng lm hng ro ngn cch mi trng nc vi cc cu trc t bo. Chng ta
cng thy, phospholipid c 2 u, mt u l gc phosphate a nc, cn u kia l gc acid k
nc. Cholesterol cng c 2 u, mt u l gc hydroxyl a nc, cn u kia l nhn steroid th
k nc (hnh 10.1a).
Nh vy, c 2 loi phn t u ging nhau ch c mt u a nc, mt u k nc.
u k nc b nc gian bo cng nh nc ni bo y nn quay vo trong, chng gp nhau,
hp dn nhau, l phn k nc tc l phn m chim lp gia hai lp kp ca mng. Phn a
nc th quay ra mt ngoi tip gip vi nc bao quanh.
Lp Lipid ny l hng ro ngn cch cc cht tan trong nc nh glucose, cc ion Cn cc
cht tan trong m nh oxy, carbon dioxide, ru th qua mng d dng.
c im ca lp Lipid ny l mm mi, c th un khc, trt i trt li d dng.
Hnh 10.1a. S cu trc ca mng.
Mt iu ng ch l s phn b ca cc Lipid trong mng rt khc nhau. T l Lipid v
protein thay i hnh nh ty theo hot tnh sinh hc ca mng. Chc nng sinh hc cng phc tp
th hm lng protein cng cao. Chng ta hy ly mng ty lp th lm v d: lp mng trong gi
vai tr chnh trong qu trnh h hp m bo v tng hp ATP nn cha nhiu enzyme oxy ho kh,
cc protein vn chuyn in t, cc ATP synthetase Mng mylein bc dy thn kinh vi nhim
v cch in do khng cn nhiu protein chc nng cc t bo schwann.
Hn th na, s sp xp cc nhm Lipid ngay gia 2 lp ca cu trc mng kp cng khng
ng u v cc thnh phn cht bo, nht l vi nhm phospholipid. mng hng cu, lp ngoi
cha ch yu phosphatidyl cholin v Sphingomyelin, cn lp trong (gip vi bo tng) cha
phosphatidyl ethanolamine v phosphatidyl serine. Nhm phosphatidylinositol cng phn b lp
trong ca mng t bo. Cc glycolipid thng lun gn mt ngoi ca mng thun tin cho
chc nng sinh hc ch nh tnh khng nguyn ca mng.
Tuy nhin, cho ti nay ngi ta vn cha hiu c ti sao mng t bo li cn nhiu loi
Lipid khc nhau nh vy.
2.2 Cc protein mng sinh hc
Cc khi protein hnh cu, ni bp bnh trn lp Lipid kp, l glycoproteit. C 2 loi
protein, mt protein xuyn mng, cn mt loi l protein ra (hay l protein ngoi vi) ch v bm vo
mt bn mt ca mng m khng thm nhp vo lp mng (hnh 10. 1b).
u phn t protein trn mt ngoi cha nhiu Carbohydrate (ch yu l Oligosaccharide)
ng vai tr cu ni tip xc v vn chuyn thng tin gia cc t bo .
Nhiu phn t protein xuyn mng lm thnh nhng knh (hoc l) qua cc cht tan trong
nc, c bit l cc ion c th khuch tn qua li gia dch ngoi bo v dch ni bo. Cc protein
ny khng phi l nhng ci ca m th ng cc cht t do qua li, m l protein c thuc tnh
chn lc, cho php mt cht ny khuch tn u tin hn cht khc. Mt s phn t protein xuyn
qua mng li l nhng protein mang (carrier) lm nhim v vn chuyn cc cht theo chiu ngc
vi chiu khuch tn t nhin, l s vn chuyn tch cc. Mt s phn t protein khc li c hot
tnh enzyme.
Hnh 10.1b. Cu trc mng t bo .
Cc protein ra thng hon ton mt bn mt pha trong ca mng v bm vo cc protein
xuyn mng, chng c chc nng v hot tnh hu nh hon ton l enzyme (hnh 10.1b)
Cc protein mng t bo m nhim cc nhim v chnh sau y: Vn chuyn cht, bm cc
ion, thc hin cc qu trnh oxy ho kh, l cc receptor, l knh dn ion, l cc enzyme phn gii
(protease, esterase v.v..), l cc ng c hoc kh c vn ng vi sinh vt, to ng ni gia cc t
bo.
2.3 Cc Glucid ca mng t bo
Cc Glucid ca mng hu nh bao gi cng ho hp vi protein v vi Lipid di dng
glycoproteit v glycolipid. Nh vy hu nh bao gi phn protein cng nm chm trong b dy
mng t bo, cn phn glucid bm pha mt ngoi mng t bo mt cch lng lo v ton b b
mt ngoi t bo c mt lp o glucid lng lo gm phn glucid ca 3 loi hp cht k trn
(glycoproteit, glycolipid, proteolycan). Lp o c gi l o glucid hay v glucid (glycocalix).
o glucid c cc chc nng quan trng nh sau: Nhng glucid thng tch in m c tc
dng xua i nhng vt c tch in m, lm cc t bo dnh vo nhau khi o glucid t bo ny bm
vo o glucid t bo khc, nhiu glucid l cc Receptor gn cc hormone v cui cng l tham
gia mt s phn ng min dch.
3. S vn chuyn cc cht qua mng
3.1. Hng ro Lipid v s vn chuyn qua mng
Nh trn ni, mng t bo ch yu l mt lp kp, ri rc nhiu phn t protein lnh bnh
trn mt lp Lipid l mt hng ro ngn khng cho nc, hot cht tan trong nc qua li gia hai
khu vc trong v ngoi t bo. Tuy nhin vn c mt s cht i qua lp Lipid kp ra hoc vo t
bo.
Mt khc, cc phn t protein cn c nhiu cch khc vn chuyn cht qua mng. Phn t
protein chim mt ch lp Lipid kp, ch l mt con ng thay th c ngha l phn t hay
ion no khng qua c lp Lipid th c th dng con ng m i qua mng c. Vy phn
ln cc protein xuyn mng l protein vn chuyn. C nhiu lai protein, mi loi c mt cch hot
ng khc nhau. Mt s protein c mt khoang cha y nc chy xuyn sut qua phn t protein
lm thnh mt con ng hay cn gi l con knh, l nhng protein knh. Li c nhng
protein mang, n gn vi cht cn c vn chuyn, ri phn t protein ny bin dng hnh thi, do
a cht c vn chuyn i qua cc khe bn trong phn t protein, nh qua mng sang mt
bn kia ca mng. Hai loi protein knh v mang u c tnh chn lc cao i vi phn t hoc ion
m n a xuyn qua mng.
S vn chuyn cc cht qua mng t bo c th thc hin qua mt trong hai qu trnh c bn:
khuch tn v vn chuyn tch cc. Khuch tn l s vn ng phn t ngu nhin ca mt cht,
lm cho tng phn t cht i qua mng, hoc lch qua khe lin phn t ca mng, hoc gn vi
mt protein mang. Nng lng khuch tn chnh l nng lng t nhin sn c ca vn ng c hc
ca vt cht. Ngc lai, vn chuyn tch cc l a cht i xuyn qua mng do kt hp vi protein
mang, li c thm s i qua ngc thang nng lng, chng hn nh i t ni c nng thp sang
nng cao. Qu trnh ny i hi phi cung cp thm nng lng t bn ngoi.
3.2. S khuch tn.
Khuch tn l s lin tc vn ng ca cc ht vt cht, ht c th l ion, l phn t nc,
l cht tan trong dung dch bt k, trong dch c th hoc l cht kh t ni c nng cao sang ni
c nng thp. S khuch tn ny ph thuc vo ni nng ca vt cht tham gia khuch tn. Ni
nng ca vt cht, vt l hc l nhit, y chnh l s chuyn ng nhit, s chuyn ng cng
nhiu th nhit cng cao v khng bao gi ngng, ch khng tuyt i th mi ngng chuyn
ng.
3.2.1. Khuch tn n thun qua lp Lipid kp
Khuch tn ca cc cht tan trong m: Ngi ta thc nghim to mt mng nhn to ch c
mt lp Lipid kp (khng c protein vn chuyn) th thy yu t quan trng nht khin mt cht tan
trong m nh oxy, nit, carbon dioxide v ru i qua mng t bo rt nhanh. Tc khuch tn
qua mng t l thun vi tan trong Lipid (Hnh 10.2).
Vn chuyn nc v cc phn t khng tan trong Lipid.
Mc d nc khng tan trong Lipid mng t bo nhng nc c vn chuyn qua mng rt
nhanh, phn ln i thng qua lp Lipid kp, mt s qua knh protein. Nc khuch tn nhanh ti
mc mt giy nc c th vo hng cu bng 100 ln th tch ca chng. Nguyn nhn cha r ti
sao nc qua nhanh, nhng ngi ta cho rng do phn t nc nh, li c ng nng cao nn phn
k nc ca mng cha kip ngn th phn t nc i qua ri.
Cc ion khng khuch tn qua lp Lipid kp tuy kch thc nh. Nguyn nhn ngn cn ion
qua mng l do in tch vi 2 c ch khc nhau:
in tch lm cho cc phn t nc gn vo ion to thnh nhng ion gn nc c kch thc
rt to nn khng qua c mng.
in tch ca ion b in tch ca lp Lipid kp xua y, khng cho lt qua mng.
Hnh 10.2. Nhng c ch c bn ca s vn chuyn qua mng t bo .
3.2.2. Khuch tn n thun qua knh protein v cnh cng ngn knh.
Ngi ta dng my tnh dng li cu trc 3 chiu ca mt protein v chng minh l
nhng knh hnh ng ni dch ngoi bo vi dch ni bo. Knh c tnh thm chn lc cao, do kch
thc, do hnh dng v do bn cht in tch c mt trong ng knh c tc ng ln cht i qua
mng.
Cng ca knh protein: Cng ny l mt phng tin kim sot tnh thm ca knh. Ngi ta
cho rng cng (hay l cnh cng ng m) l s pht trin ca c ch phn t protein vn chuyn.
Cng c th khp li hay m ra do s bin i hnh dng ca phn t protein. Natri c nhiu dch
ngoi bo, v cnh cng ca knh natri ng m pha mt ngoi ca mng t bo, cn kali c
nng cao trong t bo, cnh cng ca knh kali ng m mt trong t bo, pha gip bo tng
(Hnh 10-3).
C 2 c ch kim sot vic ng v m cng:
ng m do in th (Voltage gating) l do in th mng lm thay i hnh dng phn t
ca cng. in tch m trong mng lm cng natri ng cht, khi mt trong mng mt in tch m
th cng natri m hm lng ln natri chy vo qua knh natri. l nguyn nhn c bn ca in
th hot ng dy thn kinh khi c xung thn kinh.
ng m do cht kt ni (ligand) l s ng m knh do protein knh gn vi mt phn t
khc. Phn t gn vo c gi l cht kt ni (ligand). V d, tc dng ca acetycholin i vi
knh acetycholin. Cng ny rt quan trng i vi vic vn chuyn tn hiu t mt t bo thn kinh
ny sang mt t bo thn kinh khc.
Hnh 10.3. Vn chuyn Ion Na
+
(a) v K
+
(b) qua cc knh protein
3.2.3. Khuch tn tng cng.
Khuch tn tng cng cn gi l khuch tn thun ho (facilitated diffusion), l s
khuch tn d dng hn v tng cng tr thnh d thc hin c. Trong trng hp ny, nu
thiu vt mang th khng thc hin c s khuch tn. V c vai tr ca vt mang nn qu trnh
ny cng cn gi l khuch tn qua vt mang.
Khuch tn tng cng khc khuch tn n thun qua knh m, do mt iu quan trng l
khuch tn tng t l thun vi nng cht khuch tn. Trong khuch tn tng cng, tc
khuch tn tng dn ti mt im ti a gi l Vmax, ti th dng li d nng cht khuch tn
tip tc tng na.
C gi thuyt cho rng s d c im gii hn ti a v tc khuch tn l v cht c
khuch tn khi i qua phn t protein mang, i trong mt con ng bn trong phn t mang n
gia ng th nghn li v b dnh vo mt ni gi l im gn (binding) hoc cn gi l im tip
nhn (Receptor). Sau phi c thi gian cho protein mang thay i hnh dng khin cho phn t
khuch tn tch c ra khi im tip nhn, v tip tc l trnh i ht con ng, sang mt bn kia
ca mng t bo. Thi gian protein mang thay i hnh dng, chnh l yu t gii hn tc khuch
tn tr s Vmax. Khuch tn tng cng l c ch qua mng t bo nhng cht rt quan trng nh
glucose v nhiu acid amin. Ngi ta bit nhng phn t protein cht mang c khi lng phn
t c chng 45.000 Dalton v cn c th vn chuyn nhng mono saccharide c cu trc ging
glucose nh manose, galactose, xylose v arabinose. Insulin lm tng tc khuch tn tng cng
ca glucose ln gp 10-20 ln.
3.2.4. Cc yu t nh hng i vi tc khuch tn.
Thng thng khi ni mt cht khuch tn qua mng vi mt tc no th ngi ta hiu
l tc khuch tn thc (net diffusion) v khi dung dch mt cht c nng khc nhau hai
bn mng, th ng thi c 2 dng khuch tn qua mng vi 2 tc khc nhau. S khuch tn t
bn trong nng cao sang bn nng thp, vi mt tc cao. ng thi li c dng khuch tn
cht t bn nng thp sang bn nng cao vi tc thp hn.
Nh vy, tc khuch tn thc l hiu gia tc khuch tn ca 2 dng vn chuyn cht
theo hai chiu qua mng, l tc chng ta quan tm v n l hin tng lin quan ti s sng
ca t bo. Tc khuch tn thc chu nh hng ca 4 yu t l: Tnh thm ca mng, hiu nng
cht hai bn mng, hiu p sut qua mng v hiu in th hai bn mng.
nh hng tnh thm ca mng i vi mt cht (k hiu l P - Permeability) l tc
khuch tn thc cht qua mt n v din tch mng, di tc dng ca mt n v hiu nng
(khi khng c hiu p sut v hiu in th). Tnh thm ca mng chu nh hng ca: B dy ca
mng ( mng cng dy cng khuch tn chm); tan trong m ( tan cng cao, khuch tn cng
nhan); s lng knh protein (tc khuch tn t l thun vi s knh cho mt n v din tch);
nhit (t l thun vi khuch tn) v khi lng phn t cht khuch tn (KLPT thp th d
khuch tn, mi quan h ny rt a dng ch khng n gin).
H s khuch tn ca mng c k hiu l D (diffusion) chnh l tnh thm P ca ton mng,
do bng tnh thm P nhn vi din tch A ca ton mng.
D = P x A
nh hng ca hiu nng : Tc khuch tn thc t l vi hiu nng cht hai bn
mng.
Khuch tn thc = D (C
0
C
i
)
Trong C
0
l nng ngoi mng (out), C
i
l nng trong mng (in), D l h s khuch
tn.
nh hng ca hiu p sut: Khi c hiu p sut ln hai bn mng th c dng vn ng phn
t t bn p sut cao sang bn p sut thp.
nh hng ca hiu in th: Khi c hiu in th hai bn mng th c mt gradient in qua
mng. in tch dng hp dn cc ion m, cn in tch m y cc ion m, to nn mt chnh
lch nng . S chnh lch nng tng dn n mc xu th khuch tn do chnh lch nng
bng xu th khuch tn do hiu in th, ti lc ny h trng thi cn bng ng. nhit c
th (37
0
C), hiu in th to cn bng vi hiu nng ca cc ion ho tr mt nh Na
+
,K
+
,Cl
-
, v
hiu in th c xc nh do phng trnh Nerst:
Trong EMF l lc in ng (tc in th) gia 2 bn ca mng, C
1
, C
2
l nng ion
bn 1 v bn 2 ca mng. Tnh phn cc, tc du hiu in th bn 1 trong phng trnh trn l
dng (+) i vi cc ion m, v l m (-) i vi cc ion dng. H thc ny l cc k quan trng
hiu bn cht ca s truyn xung thn kinh.
3.2.5. Khuch tn nc v thm thu.
Nc l cht c s phn t nhiu nht i qua mng. Nc thng khuch tn qua mng t
bo. Ngi ta tnh rng trong 1 giy ng h lng nc vo v ra khi hng cu bng khong
100 ln th tch ca chnh hng cu. Tuy vy bnh thng vn c s cn bng gia lng vo v
lng ra. Cn bng ny c iu ho chnh xc n mc s phn t ra bng ng s phn t vo.
Nh vy khng c dng vn chuyn thc (net transport). Tng s lng nc ang c trong hng
cu gi nguyn khng suy suyn v th tch. Tuy nhin, trong mt s iu kin c th pht sinh hiu
nng nc (tc l chnh lch nng nc) qua hai bn mng ngn hng cu.
p sut thm thu:
S ht thm thu (tc nng mol) c tm quan trng ch p sut thm thu l do s ht
trong mt th tch, ch khng phi do khi lng ca cht tan trong dung dch. S ht ca cht
khng thm qua mng, d ht to hay nh khng nh hng, m c mi ht khng thm qua mng l
chon ch ca mt phn t nc. Ht to, ht nh u trao i nng lng sang nhau trong vn ng
phn t, tt c u c mt ng nng trung bnh K bng nhau tt c, m gi tr ca K theo
phng trnh:
K= mv
2
/2 .
Trong m = khi lng; v= vn tc ca ht
Mi ht thm thu l mt phn t ca cht khng phn ly, hoc l mt ion ca phn t phn
ly.
Khi nim v Osmol kilogam so vi nng Osmollit:
p sut thm thu c gi tr bao nhiu l do s ht cht tan ch khng do khi lng cht tan.
V vy nng cht tan to p sut thm thu khng biu th bng s gam m phi biu th bng s
ht cht tan. n v nng s ht thm thu l Osmol.
Mt Osmol l s phn t c trong mt phn t gam cht khng phn ly (khng ion ho), v d
glucose l cht khng phn ly v c s phn t gam bng 180, vy 180 gam Glucose l mt osmol.
Trong trng hp NaCl l cht phn ly hon ton trong dung dch nc v phn t gam NaCl l
58,5g; nh vy 58,5g NaCl l 2 osmol. Khi dung dch c 1 osmol cht tan trong 1 kilogam nc
(1kg), ta ni l nng osmol kilogam (osmolality) ca dung dch l 1 osmol cho 1 kg (1
osm/kg).
Trong sinh l hc ngi ta thng dng n v miliosmol (mosm). Dch ni bo v dch ngoi
bo c nng osmollit (osmolarity). Nng osmollit (osmolarity) c gi tr xp x nh nng
osmolkg (osmolality) (chnh lch nhau khng ti 1%).
Trong tng quan nh lng gia nng osmolkg v p sut thm thu, cn thit phi phn
bit p sut thm thu (osmotic pressure) v nng osmollit (osmolarity) l 2 khi nim khc
nhau. p sut thm thu l lc biu th bng kg/cm
2
hoc mmHg, cn nng osmol l nng
biu th bng s ht/lt. 37
0
C nng 1 miliosmol/lt to p sut thm thu 19,3 mmHg. Dch c
th c 300 mosm, tnh ra l 5790 mmHg, nhng khi o thc t ch c chng 5500 mmHg. C s
chnh lch ny l do trong dch c th, nhiu loi ion nh Na
+
, Cl
-
hp dn nhau nn vn ng nh
mt ht phn t, ch khng nh 2 ht ion. S ht osmol gim th tc dng thm thu gim. V vy
p sut thm thu o thc ch chng 0,95 tr s tnh ton t nng osmol.
3.3. Vn chuyn tch cc.
Khuch tn tch cc l khuch tn ngc chiu bc thang in ho. Bc thang in ho
(Electrochemical gradient) l tng cc lc to ra khuch tn, gm hiu nng , hiu in th v
hiu p sut. Khuch tn th ng l i xui chiu cc bc thang . S sng t bo nhiu khi i
hi phi khuch tn ngc bc thang, v d ta phi a K
+
vo t bo l ni c nng K
+
cao
hn bn ngoi rt nhiu, hoc phi a Na
+
t t bo ra dch ngoi bo mc d l dch ngoi bo
c nng Na
+
cao hn trong dch bo. S vn chuyn nh vy l i ngc dng ln dc. Trong s
cc cht c vn chuyn tch cc qua mng t bo gm Na
+
, K
+
, Ca
2+
, H
+,
Cl
-
,i
-
, ion st, ion urat,
nhiu loi ng, nhiu acid amin.
Vn chuyn tch cc nguyn pht v th pht.
Ngi ta chia vn chuyn tch cc lm 2 loi tu theo nng lng c dng. Loi nguyn
pht dng nng lng trc tip t phn gii ATP hoc hp cht phosphate giu nng lng khc.
Loi th pht dng nng lng ly t bc thang nng ion, bc thang ny l th pht, l h qu
ca s vn chuyn tch cc trc . C 2 loi vn chuyn tch cc ny u dng protein mang l
phn t xuyn qua b dy ca mng ging nh trong khuch tn tng cng. Tuy nhin, protein ny
c cch hot ng khc so vi khuch tn tng cng ch protein chia nng lng cho cht c
vn chuyn.
3.3.1. Vn chuyn tch cc nguyn pht.
Bm Natri Kali l c ch c nghin cu rt chi tit, l c ch bm ion Na
+
ra khi t
bo, ng thi bm ion K
+
vo trong t bo. Loi bm ny c mi t bo.
Bm Natri Kali l mt protein mang gm 2 phn t protein hnh cu, mt to c KLPT
chng 100.000 v mt nh c KLPT chng 55.000. Protein to c 3 im quan trng v chc nng:
C 3 trung tm tip nhn ion Natri, cc trung tm ny nm phn protein th vo bn trong t bo;
C 2 trung tm tip nhn ion kali nm phn th ra bn ngoi t bo v phn th vo trong, gip
vi trung tm gn Natri c hot tnh ATPase.
Khi c 3 ion natri gn vo u trong v 2 ion kali gn vo u ngoi ca protein mang th hot
tnh ATPase c pht ng. Phn t ATP tch ra ADP v gii phng mt lin kt giu nng lng.
Ngi ta cho rng nng lng ny lm thay i hnh dng phn t protein mang, do y Na
+
ra
ngoi v K
+
vo bn trong.
Bm Na
+
- K
+
c vai tr kim sot th tch t bo, l chc nng rt quan trng. Ta bit rng
trong t bo c nhiu ion m (protein, cc cht hu c) c xu th hp dn ion dng. Nu hp dn
c th s c qu nhiu ion trong t bo to p sut thm thu ht nc vo lm t bo phnh ra v
v. Nhng bm ny a 3 ion Na
+
ra m ch cho 2 ion K
+
vo, tc l thc t cui cng c 1 dng
ion dng chy ra ngoi t bo nh c tc dng thm thu a nc ra ngoi t bo. Mi khi v
l do no t bo phnh nc th t ng pht ng my bm Na
+
- K
+
hot ng tng cng, nh
m th tch t bo duy tr bnh thng.
Bm Na
+
- K
+
c bn cht sinh in v c mi vng quay ca bm thc t y c 1 ion
dng ra ngoi (3 Na
+
- 2K
+
), to in tch dng bn ngoi, in tch m bn trong t bo.
Bm calci l mt loi bm vn chuyn tch cc nguyn pht. Nng ion calci trong bo
tng ch bng 1/10.000 dch ngoi bo, nh hot ng ca 2 loi bm Calci. Mt loi bm nm
trn mng t bo, bm Calci ra ngoi t bo. Mt loi bm na, bm ion Calci vo bo quan, v d
vo mng ni bo tng hoc vo tylp th. Phn t protein mang cng nm xuyn qua mng t bo
v cng c hot tnh ATPase ging nh trng hp bm Natri.
S bo ho ca vn chuyn tch cc: S vn chuyn tch cc c th b bo ho, tc l t ti
im gii hn, gi l V
max
ging nh trng hp gii hn ca khuch tn tng cng. y cng
vy, tc phn ng b gii hn do cn c gi cho protein bin i hnh dng m gn hay nh
cht c vn chuyn.
S tiu dng nng lng trong vn chuyn tch cc. Nng lng dng vn chuyn cht,
khng k phn mt theo nhit trong phn ng ho hc, l t l theo mc tp trung cht, cn gi
l mc tng nng cht. Khi vn chuyn tch cc mt bn mng c nng cao gp hng
trm ln bn kia mng th tn nng lng gp 2 ln so vi to nng cao gp 10 ln. Ni cch
khc, nhu cu nng lng, t l thun vi logarit ca s tng nng cht, theo cng thc:
Nng lng ( calo/osmol) =1400log C
1
/ C
2 .
C nhiu trng hp t bo tiu dng rt nhiu nng lng vo vic ny, v d t bo ng thn
v mt s tuyn dng ti 90% nng lng ca mnh tp trung nng cht.
3.3.2. Vn chuyn tch cc th pht, ng vn chuyn v vn chuyn i ch.
Vn chuyn tch cc th pht l loi vn chuyn dng nng lng gin tip, tc l mn th
nng khuch tn ca mt chnh lch nng c to lp trc do vn chuyn tch cc
nguyn pht.
Ta bit rng, bm natri to mt nng cao ion natri ngoi t bo. Nng cao ny l mt
th nng c xu hng l ion natri khuch tn tr vo, khi tr vo th xy ra hin tng nhn tin
km theo mt cht khc. Tu theo cch thc em i theo m gi l ng vn chuyn vi natri hay
l vn chuyn i ch vi natri. Nhng cht i cng chiu vi natri vo t bo th ng vn chuyn
cn nhng cht cn i ngc chiu vi natri ra ngoi th vn chuyn i ch.
Glucose v acid amin qua mng t bo do c ch ng vn chuyn vi natri: Protein mang c
2 trung tm tip nhn phn ngoi ca phn t, mt trung tm nhn natri, mt trung tm nhn
glucose. Natri c nng bn ngoi t bo cao hn rt nhiu so vi bn trong nn th nng i vo
cung cp nng lng a lun c glucose vo theo. Protein mang s c bin i hnh dng ph
hp chuyn 2 cht qua mng. Protein mang c c im l chng no mi tip nhn mt cht
natri th cha bin dng vn chuyn, ch khi no tip nhn 2 cht th mi t ng bin dng v
khi chuyn lun c 2 cht qua mng trong t bo. ng vn chuyn acid amin cng tng t mi
mt nh ng vn chuyn glucose, ch khc l c ti 5 loi protein vn chuyn tng ng vi 5 acid
amin.
C 2 c ch ng vn chuyn nh sau:
Th nht l ng vn chuyn Natri Kali hai Clo, l qu trnh a 2 ion Cl
-
vo t bo,
i cng chiu vi ion K
+
v 1 ion Na
+
, u i vo.
Th hai l ng vn chuyn Kali v Clorua a K
+
v ion Cl
-
t bn trong t bo, 2 ion ny
cng nhau ra ngoi. Ngoi ra cn c ch ng vn chuyn cc ion I
-
, st, urat
Cc ion Ca
2+
v H
+
vn chuyn i ch vi Na
+
. C 2 c ch quan trng l i ch Na
+
- Ca
2+
v i ch Na
+-
- H
+
. Khi i ch Natri Calci th ion natri i vo t bo, i ch cho ion Calci i ra,
c 2 ion u gn ln mt phn t protein mang, phn t ny bin i hnh dng theo phng thc
i ch. Phng thc ny b sung cho vn chuyn nguyn pht, calci mt s t bo. C ch i
ch natri hydro l mt qu trnh rt quan trng trong ng ln ca thn, ion natri t lng ng i
vo t bo ng, i ch cho ion hydro t t bo ng i ra dch lng ng, nh vy va thi c
ion H
+
cn b ca s chuyn ho, va gi c ion natri cn cho c th. y l mt qu trnh rt
quan trng m t lu nay ngi ta vn thng ni n l s i ch Na
+
- H
+
.
Trong s vn chuyn i ch cn phi k n trao i cation gia mt bn mng t bo l
Ca
2+
hoc Na
+
, v bn kia mng l Mg
2+
hoc K
+
. Li c trao i anion gia ion Cl
-
i mt chiu v
ion bicarbonat hoc sulfat i theo chiu ngc li.
4 . Vn chuyn tch cc qua lp t bo.
C ch vn chuyn qua lp t bo c 2 bc chnh: Vn chuyn tch cc cht qua mng t bo
vo trong t bo v khuch tn n thun hoc tng cng qua mng t bo ra pha bn kia ca
t bo.
Hai bc vn chuyn trn ch l mt s n gin ca s vn chuyn qua mt lp t bo.
Trong thc t a dng hn rt nhiu v d vn chuyn t trong lng ng qua lp biu m vo h
tun hon nh rut, ng thn, hoc vn chuyn theo chiu ngc li a cc cht ra pha lng
ng nh ti mt, tuyn ngoi tit. Pha no ca biu m l vn chuyn tch cc (nguyn hoc th
pht) v pha bn no l khuch tn n (n thun hoc tng cng) l tu tng c quan.
YU CU CN NM
CHNG X: S VN CHUYN CC CHT QUA MNG
Khi nim v mng. Thnh phn cu to ca mng. S vn chuyn cc cht qua
mng
Cu 1: Thnh phn cu to ca mng?
Cu 2: S vn chuyn cc cht qua mng?
Chng XI
MI LIN H GIA CC QU TRNH
TRAO I CHT
Trong cc t bo v trong cc c th sng s trao i cht c mi lin quan tng h ln
nhau. Mi lin ny c th hin 2 lnh vc ch yu l nguyn liu v nng lng.
Mi lin quan v nguyn liu l kh nng chuyn ho mt cht ny thnh cht kia thng qua
mt s sn phm trung gian chung.
Mi lin quan v nng lng c biu hin ch l khi phn gii mt hp cht no , nng
lng c tch ly bng s hnh thnh hp cht ATP hp cht cao nng ATP ny c s dng
cho phn ng thu nng lng v cc qu trnh sinh tng hp cc cht khc nhau trong c th. V d
ATP c to thnh trong qu trnh ng phn v quang phosphoryl ho (quang hp), trong qu
trnh phosphoryl oxy ho (h hp), phosphoryl vi oxy ho thng qua chu trnh Krebs v chui vn
chuyn in t ca cc acetyl CoA c to thnh t saccharide, cc acid bo hay cc acid amin.
Nh kh nng chuyn ho tng h gia cc cht m cc c th thch ng c vi mi
trng. V d mt s ng vt vng n i do d tr c mt lng lipid ln nn bo m
cung cp nng lng v cc cht cn thit cho c th s dng trong thi gian ng ng. thc
vt, vo ma ng xy ra s chuyn ho tinh bt thnh ng v cht bo nn cy c kh nng chu
lnh. Sau y chng ta xem xt mi tng quan ca s trao i tng cp hp cht.
1. Mi lin quan gia trao i saccharide v lipid.
Khi phn gii saccharide (glucose) to thnh hp cht trung gian l Dihydroxyaceton
phosphate, cht ny c s dng tng hp nn glycerol. Cn t glyceraldehyd-3- phosphate s
phn gii v hnh thnh acetyl-CoA v tip tc c tng hp thnh acid bo. Glycerol kt hp vi
acid bo thnh lipid.
Dihydroxyaceton phosphate glycerol
ccharide Lipid
Gliceraldehyt-3-phosphate acetyl-CoA Acid bo
Ngc li, sn phm ca s phn gii lipid l glyxerol v acetyl-CoA li l nguyn liu
tng hp nn saccharide: glyxerol to thnh fructose -1,6 diphosphate. Acetyl-CoA i vo chu
trnh glyoxylic ( mt s thc vt, vi khun, nm mc) n s to thnh oxaloacetate, tip theo thnh
phosphoenolpyruvate v tng hp thnh glucose (hnh 11.1,11.2)
Hnh 11.1: S chuyn acid bo d tr thnh ng trong s ny mm ca ht.
hnh 11.1, c mt vng ca chu trnh glyoxylat c 2 phn t acetyl-CoA tham gia s to ra
c 1 phn t succinate. Succinate chuyn vo chu trnh Krebs to ra phn t oxaloacetate.
Acid bo
- oxy ho
Acetyl - CoA
CH
3
-CO-SCoA
Malate
Oxaloacetate
citrate
izocitrat
glyoxylate
Acetyl - CoA
0
CH
3
-C-SCoA
Succinate
-OOC-CH
2
-CH
2
-COO
-
Chu trnh
glyoxylic
Succynyl-CoA
Succinate
Fumarate
Malate
Oxaloacetate
citrate
Izocitrate
-Ketoglutarate
Phosphoenol pyruvate
Fructose-6-phosphate
Glucose-6-phosphate
=

=
OOC-C-CH
2
-COO
-
O
6
CO
2
Chu trnh
Acid-citric
Oxaloacetate b kh carboxyl v photphoryl ho thnh frutose - 6- phosphate, sau to thnh
glucose. Nh vy 4 phn t acetyl-CoA cho 2 phn t succinate, tip tc l 2 phn t oxaloacetate.
Oxaloacetate loi i 1 CO
2
, qua qu trnh bin i s thnh 1 phn t glucose.
Lipid

Acid bo Acetyl-CoA
Glycerol
Glycerol
Kinase
Glycerol-3 Photphate
NADH
NADH+H
+
Dihydroxyaceton phosphate
Hnh 11.2: Lipid d tr trong ht c oxy ho thnh acetyl-CoA v dihydroxyaceton
phosphate trong qu trnh ny mm- c 2 c cht ny s to thnh glucose thc vt. Cn nh rng
acetyl-CoA khng phi l c cht cho s to thnh glucose ng vt.
2. Mi lin h gia s trao i saccharide v protein.
S phn gii saccharide to ra mt s -cetoacid, khi amin ho, chng s to thnh cc acid
amin tng ng:
Pyruvate alanine
-cetoglutarate glutamate
oxaloacetic aspartate
Cc acid amin ny li tip tc chuyn ho bng con ng ring to nn cc acid amin khc
nh glutamate thnh proline, aspartate thnh lysine, Methionine, Threonine, Isoleucine Ngc
li, mt s acid amin (alanine, phenylalanine, tyrosine, histidine, tryptophan, serine, cystein,
glutamate, proline, aspartate) c coi l acid amin to glucose.
Ngoi ra, gia qu trnh d ho saccharide (chu trnh Krebs) v qu trnh d ho acid amin
(chu trnh urea) c nhng giai on to ra cc sn phm trung gian ging nhau. l cc aspartate,
glutamate, fumarate. iu chng t c mi lin quan gia trao i saccharide vi trao i protein
(hnh 11.3, 11.4, 11.5).
Hnh 11.3: Mi lin quan gia chu trnh Krebs (bn tri) vi chu trnh urea (bn phi) thng
qua cc sn phm trung gian aspartatarginino succinate, Fumarate, acginosuccinate, oxaloacetate...
Hnh 11.4: Chu trnh urea v cc phn ng cung cp nhm amin cho n
Fumarate
Malate
Oxaloacetate
Glulutamate
Arginine
ornithine
Acginino
succinate
urea
citrullin e
Cacbamoil
phosphate
Aspactat e
ketoglutarate
Cc Acid amin
Glutamine (t m nc
chit gan)
Chuyn amin ho thnh
-Ketogutarate
Alanine (t c)
Glutamate
n bc (2b) ca
chu trnh urea
Ty th
citrulline
Acginiosuccinate
ornithine
citruline
Aspartate
ornithine
Fumarat
Hnh 11.5. Con ng phosphoenolpyruvate n glucose-6-phosphate l chung cho s bin
i sinh tng hp ca nhiu tin cht khc nhau hnh thnh saccharide trong ng vt v thc vt .
Glucose mu
Glycogen
Cc
glucoprotin
disaccharide
Cc
monosaccharide
Thc vt
Sacarose
ng vt
Glucose - phosphate
Nng lng
phosphoenolpyruvat
C nh C0
2
Hnh 11.6: Tng qut ca sinh tng hp cc acid amin. Cc tin cht t qu trnh ng phn,
chu trnh acid citric v con ng pentose photphate.
3-phosphat glycerate Serine
Ribose-5-
phosphate
Histidine
Eritrose-4-
phosphate
Tryptophan
Phenylalanine
Tyrosine
Glycine
cycteine
Alanine
Valine
Leucine
Photphoenolpyruvate
Pyruvate
Glucose-6 - phosphatase
Glucose
3. Mi lin quan gia s trao i lipid v protein.
Acid bo l tin cht ca mt s acid amin thng qua cc chu trnh Krebs (mt s acid amin
c tng hp t acid - cetoglutaric) hoc qua chu trnh acid glyoxylic) to ra oxalo acetate, cht
ny sau b loi carboxyl to thnh acid pyruvic. T 2 cht ny tng hp nn mt s acid amin
(hnh 11.6)
Ngc li, mt s acid amin (leucine, isoleucine, tryptophan) khi phn gii s to thnh
acetyl-CoA, t tng hp nn acid bo. Mt s acid amin khc (alanine, cysteine, serine) li b
phn gii thnh acid pyruvic. Theo con ng tng hp mi glucose, acid pyruvic s to thnh
glyceraldehyd 3- phosphate. T cht ny s tng hp nn glycerol. S chuyn ho protein thnh
lipid c th khi qut trong s sau (hnh 11.7, 11.8).
Hnh 11.7. S chuyn ho acid bo thnh acid amin
Hnh 11.8: S chuyn ho Protein thnh lipid
4. Mi lin quan gia trao i saccharide v acid nucleic
Khi phn gii glucose theo chu trnh pentose phosphate s to thnh ribose 5-phosphate. T
cht ny s to nn phosphoribosyl- pyrophosphate dng lm nguyn liu cho tng hp cc purine v
pyrimidine (hnh 11.9)

Phenylalanine
Tyrosine
Leucine
Lysine
Tryptophan
Alanine
cystine
Glycine
Serine
Threonine
isoleucine
Leucine
Tryptophan
Protein
Acetoacetyl - CoA
Acetyl - CoA
Acid bo
Acid pyruvic
Glyceraldehyd -
Glycerol
Lipid

Phosphoribosylpyrophotphate (PRPP)
5- phosphoribosyl alanine
acid inozinic (IMP)
Hnh 11.9: Con ng tng hp cc nucleotid adenine v guanine
Mt s nucleotide cng c vai tr i vi s sinh tng hp cc oligosaccharide v
polisaccharide. V d, uridin diphosphate glucose (UDP- glucose) dn xut nucleotide ca ng, n
l cht cho gc glucose.
5. Mi quan h gia trao i protein v acid nucleic.
Cc acid amin glutamine, acid aspartate l nguyn liu tng hp nhn pyrimidine (hnh 11,9)
cc acid amin glutamine, lysine, acid aspartic tham gia tng hp nhn purine.
Cc base purine v pirimidin ng vai tr rt quan trng trong qu trnh tng hp acid
nucleic nh DNA, rRNA, mRNA v t-RNA.
Adenilo Acid xanthylic
Succinic

AMP GMP
ADN GDP
ATP GTP
Ribose 5- phosphate
6. Mi quan h gia s trao i lipid v acid nucleic
S trao i ca lipid v acid nucleic c rt t mi lin quan trc tip, chng ch lin quan
gin tip thng qua trao i saccharide v protein.
Mt s dn xut nucleoside diphosphate nh cytidine diphosphate choline v cytidine
disphosphate ethanolamine tham gia vo qu trnh sinh tng hp phosphatid vi vai tr cht cho gc
choline v ethanolamine (hnh 11.10, 11.11)
N
5
, N
10
- metilen
H
4
folate
7,8 Dihydrofolate
Gliycine
Serine
+
Hnh 11.10: Tng hp Thymidylate
Hnh 11.11: Tng quan cc con ng hnh thnh phosphotidylcholine v phosphtidyl
ethanolamine
Trong cc chng trao i cht chi gii thiu qu trnh chuyn ho trao i cht ring l.
Nhng c th sng l mt khi thng nht ton vn, qu trnh trao i c mi lin h hu c vi
nhau.
Ethanolamine
CDP
-
ethanolamine
choline
CDP-choline
3 ado Met
Phosphotidyl
Ethanolamine
ng vt
c v
Dioxylglyxerol
CMP
Serine
Ethanolamine
Phosphotidyl
Serine
Seri
CMP
CDP - diaxil
glixerol
Co
2
Decarboxyho
Vi khun
v nm men
CMP
3 ado Hcy
Phosphotidyl
choline
Trong c th, cc qu trnh trao i c lin quan mt thit vi nhau v c s thng nht iu
ho. Sn phm phn gii ca mt cht ny li l nguyn liu tng hp ca cht khc. Nng lng do
s phn gii ca cht ny li cn dng cho qu trnh tng hp mt cht khc.
Tuy nhin cn lu rng, vai tr v tm quan trng ca s trao i ca mi cht l khc nhau.
S trao i Saccharide v lipid c ngha ln v mt cung cp ATP cho cc qu trnh thu nng lng.
Tt c cc phn ng ca qu trnh trao i cht u phi c enzyme xc tc. Mt s chuyn ho li
c iu ho bi cc cht km hm hoc cc hormone c bn cht protein. Bi vy s trao i
protein c vai tr iu ho theo nhng c ch nghim ngt i vi ton b qu trnh trao i cht m
bo trng thi cn bng ca c th.
Ngoi ra, nh cc yu t iu ho bn trong c th v bn ngoi nh horcmone, nng
enzyme, nng c cht, s c mt cc cht kch thch v km hm v.v.. m cc qu trnh sinh tng
hp hay phn gii cc cht din ra mt cch chnh xc v tit kim nht.
YU CU CN NM
CHNG XI: MI LIN H GIA CC QU TRNH TRAO I CHT
Mi lin quan gia trao i saccharide v lipid. Mi lin h gia s trao i saccharide
v protein. Mi lin quan gia s trao i lipid v protein. Mi lin quan gia trao i
saccharide v acid nucleic. Mi quan h gia trao i protein v acid nucleic. Mi quan h
gia s trao i lipid v acid nucleic
Cu 1: Mi lin quan gia trao i saccharide vi lipid v protein?
Cu 2: Mi lin quan gia trao i acid nucleic vi saccharide; protein v lipid?
TI LIU THAM KHO
1. Trn Th n, L Don Din, ng Hnh Phc, Nguyn Th Thnh, L Ngc T, Phm
nh Thi. Sinh ho i cng tp I. Nh xut bn i hc v trung hc chuyn nghip, H Ni,
1972.
2. Trn Th n, L Don Din, ng Hnh Phc, Nguyn Th Thnh, L Ngc T, Phm
nh Thi. Sinh ho i cng tp II. Nh xut bn i hc v trung hc chuyn nghip, H Ni,
1974.
3. V Kim Bng, Nguyn ng Hng, Nguyn Vn Kim, Trn Th Lc, V Th Th, L
Khc Thn. Bi ging ho sinh i cng. Nh xut bn i hc v gio dc chuyn nghip, H
Ni, 1991.
4. Nguyn Hu Chn,Trn Th n, Nguyn Th H, Nguyn Nghim Lut, Hong Bch
Ngc, V Th Phng. Nhng vn ho sinh hc hin i tp I. Nh xut bn KHKT, H ni
2000.
5. Nguyn Hu Chn, Nguyn Th H, Nguyn Nghim Lut, Hong Bch Ngc, v Th
Phng. Ho sinh. Nh xut bn Y hc, H ni 2001.
6. nh H, ng Th Hoi An, Nguyn Th Ho, Phm Th Mai, Trn Thanh Lan
Phng, Th Thanh Thu, L Xun Trng. Ho sinh Y hc. Nh xut bn Y hc chi nhnh
TP. HCM 2003.
7. Nguyn Tin Thng, Nguyn nh Huyn. Gio trnh Sinh ho hin i. Nh xut bn
Gio dc 1998.
8. L Khc Thn, Nguyn Th Phc Nhun. Gio trnh sinh ho hc ng vt, Nh xut
bn nng thn, 1974.
9. L c Trnh. Hormon. Nh xut bn Y hc 1998.
10. Straub F.B. Ho sinh hc (Ti liu dch). Nh xut bn KHKT, H ni 1973.
11. Berge, Jeremy M ; Tymoczko, John L . ; and Stryer, Lubert. Biochemistry. W. H.
Freeman and Co. New York 2002.
12. Cooper, Geoffrey M. The Cell A molecular Approach 2
nd
ed. Sinauer Associate, Inc.,
Sunderland (MA) 2000.
13. Donald Voet ; judithg .Voet. Biochemistry 2
nd
ed ., John Wiley & Son, Inc. New York
1995 .
14. Gilber, Scott F. Developmental Biology. 6
th
ed. Sinauer Associates inc, Sunderland
2000.
15. Hames, B.D.; Hooper N. M.; Huoghton J.D. Instant note in Biochemistry, Bios
Scientific Publishers 1998.
16. Lehninger, A, L; Nelson, D,C ; Cox, M,M. Principles of Biochemistry, 2
nd
ed., Worth
Publishers, New York 1993.
17. Lodish, Harvey; Ber, Arnold; Zipursky, S. Laurence; Matsudaira, Paul; Baltimore,
Davi; Darnell, Jame E. Molecular Cell Biology . 4
th
ed., W.H. Freeman & Co ., New York 1999.
18. Nussey, S.S. and Whitehead, S.A. Endocrinology, An Integrated Approach, Bios
Scientific Publishers. Ltd .,Oxford,UK 2001.
19. Robert Horton, H.; Moran Laurence A.; Raymond S. Ochs; David Rawn, J.; Gray
Scrimgeour, K. Principles of Biochemistry, 2
nd
ed., Prentico-hall international inc, 1996.
20. Stryer, L. Biochemistry, 4
th
ed ., W.H. Freeman and Company, San Francisco 1995.
21. Cc website: www.microbes.otago.ac.nz/.../ biocontrol/protozoa.htm; Dopamine receptor
figure courtesy of www.sane.org.uk/; niko.unl.edu/bs101/ notes/slide3_8.html; www.
tulane.edu/biochem/med/igg.htm; whole mouse IgG2a molecule; users.rcn.com/.../
C/CellSignaling.html; RNA Verion of the genetic code; www.chemicalgraphics.com/. ../DNA/gem-dna.jpg;
genetics.gsk.com/ graphics/dna-big.gif; www.ocf.berkeley.edu/ ~bsj/submissions.html; www.columbia.edu/
cu/opg/pub/pub.html; ...

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-phosphateric Acid adenoseine 3

-phosphateric Acid adenoseine 2

-adenilic) (Acid acid 3

-adenilic) (Acid adenilic chu trnh)

Hnh thnh Tng hp Ct ri RNA v

Nng lng hot ho khng xc tc.

Thn kinh trung ng

Hormon gii phng(ng)

Hormon cui cng

Cc hormone gii phng

to thnh lin kt ceto acyl CoA

to thnh mt acyl CoA

P c G c metyl ho v tr 7 v c 3 gc phosphate. CAP

OH bao gi cng l C-C-A,

C (Timin Pseudo uridine Cytidin) gip cho t-RNA nhn

(Hnh 9.10). C l v th m chui nh K ca chut l 95% K v ch c 5% l . ngi th

so vi chut; Immunoglobulin ngi cha mt lng

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