TRNG I HC QUC GIA TP H CH MINH

I HC BCH KHOA
KHOA K THUT HA HC

Mn hc:

C T THC PHM
TI:

RU V C TNH CA
RU
GVHD:

Ts. Phan Ngc Ho

HVTH: Nguyn Thanh Sang

Cao Vit Cng
inh Trng nh
Xun Hng
Phan Th M Dung
Hunh Dng Ngc Uyn

Thng 4/2016

MC LC
DANH MC HNH...........................................................................................................
1.

S hp thu, khuch tn v o thi ru (methanol, ethanol, propanol.v ru

bc cao)................................................................................................................................
4
2.

S phn gii ru.......................................................................................................

2.1

3.

S phn hy methanol, ethanol thnh acetaldehyde v cc hp cht gy c.......

a.

Alcoldehydrogenase (ADH)..............................................................................

b.

Catalase.............................................................................................................

c.

H thng oxy ho ca ty th (cytochrome)........................................................

2.2

S chuyn ha acetaldehyde v cc hp cht gy c..........................................

2.3

Qu trnh oxy ha acetic acid v cc hp cht gy c trong chu trnh Krebs......

S ri lon trao i cht do oxy ha ru..................................................................

3.1

S chuyn ha ru trong c th..........................................................................

3.2

Ri lon trao i cht do oxy ha ru...............................................................

a.

S gim oxy huyt v hoi t gan....................................................................

b.

Qu trnh collagen v s ha x......................................................................

c.

Chng to ty th................................................................................................

d.

S nhim m...................................................................................................

4.

Dc hc v c tnh ca acetaldehyde v cc hp cht gy c.............................

5.

nh hng ca acetate.............................................................................................

6.

nh hng ca ethanol ln mng t bo..................................................................

6.1

nh hng ha l ca ru ln mng t bo......................................................

6.2

nh hng ti cc thnh phn ha hc ca mng t bo....................................

6.3

Cc hu qu chc nng ca s thch ng ca mng t bo..................................

TI LIU THAM KHO................................................................................................

DANH MC HNH
Hnh 1: S chuyn ho methanol v ethanol thnh aldehyde.............................................
Hnh 2: Qu trnh chuyn ho nhn heme ca cytochrome sinh ra cc hp cht c.........
Hnh 3: Con ng chuyn ha ru thnh acetaldehyde...........................................
Hnh 4: H renin-angiotensin...........................................................................................
Hnh 5: Tc ng acetate n gan....................................................................................
Hnh 6: Phn t etanol y cc phn t lipid v ph v s sp xp ca chng................
Hnh 7: Mt receptor ca protein mng cho hp thu etanol..............................................
Hnh 8: Tc ng ca ru ln mng t bo.....................................................................

1. S hp thu, khuch tn v o thi ru

Ethanol c cng thc cu to l C2H5OH. Vi tnh i nc cao nn chng c kh
nng khuch tn rt nhanh vo c th (dung lng phn b trung bnh (0.6 L/kg) khi
ru c ung vo, n s c truyn mt cch th ng t ming n thc qun ti
d dy v xung rut. kh nng hp thu ru vo c th ph thuc vo thi gian tip
xc ca chng vi cc t bo biu m, nhng ch yu l s phn b mch cc t bo
biu m ny s to ra s chnh lch nng ru gia ng tiu ha v mch mu.
Ru thm qua thnh d dy rt t, ch yu qua thnh rut non vo mu [1]. Nhng
ngi c van mn v - nm gia d dy v rut non nhy cm, sm co tht, th phn
ngm ru chm hn ngi khc. D dy c cha hay khng cha n, thc ung
cng nh hng ng k n tc hp thu ru vo mu. Ngi ta lm th nghim
thy ru khi ung trong lc i lm cho nng ru trong mu tng cao hn so vi
khi ung lc no. C th cc n km lm tng kh nng oxy ha ru dn n gim
tc i vo mu ca chng. Nng ru cng cao th tc khuch tn ca chng
ti cc c quan cng nhanh, c bit ti gan, thn, l lch v no [2].
Sau khong thi gian t 30-60 pht ung vo, nng ru c thit lp cn
bng trong tt c cc c quan k c trong phi thai ni c mng nhau bo v, qu trnh
khuch tn ru cng ch chm hn m thi.
Tip sau giai on cn bng, nng ru trong mu bt u gim vi tc
trung bnh khong 100-120 mg/kg/h ch yu qua trao i cht gan, phn cn li
c o thi qua ng phi v thn.
2. S phn gii ru
2.1 S phn hy methanol, ethanol thnh acetaldehyde v cc hp cht gy c
[3, 4]
Qu trnh oxi ho alcohol thnh aldehyde thng qua 3 con ng khc nhau,
c thc hin nh enzyme alcoldehydrogenase, catalase v h thng oxy ho ca vi
th. T l alcohol b oxi ho bng cc con ng khc nhau s khc nhau. H thng vi
th c th oxi ho c khong 9% lng alcohol thu np t ngoi vo, trong khi ,
catalase ch c th oxi ho alcohol khong 1%, trong khi , khong 90% lng
alcohol thu np t ngoi vo s c oxi ho bi alcoldehydrogenase. Mi mt c
quan s c mt con ng oxi ho ch o. V d nh gan, hu ht alcohol b oxi

ho bi Alcoldehydrogenase, trong khi , cc t bo no, alcohol b oxi ho bng

hai con ng cn li.

Hnh 1: S chuyn ho methanol v ethanol thnh aldehyde

a. Alcoldehydrogenase (ADH)
Alcoldehydrogenase l enzyme ng vai tr chnh trong qu trnh chuyn ho
ny. ADH l mt enzyme c cha nhm ngoi NAD+. ADH l mt loi enzyme nm
trong t bo cht, c tm thy gan, ng tiu ho, thn, nim mc mi, tinh hon, t
cung nhng khng c trong cc t bo no.
Kh nng xc tc ca ADH ng vt c v rt ln. Ngoi methanol, ethanol,
ADH ny cn c kh nng chuyn ho cc alcohol mch di hn, thm ch l c sterol.
V c ch, enzyme ADH s chuyn 1 ion H+ t alcohol sang cho cofactor NAD+, to
thnh sn phm kh l aldehyde v cofactor NADH. Tuy nhin, ADH chuyn bit cho
4

kh nng chuyn ho ethanol hn l cc alcohol khc. In vitro, tc chuyn ho

methanol ch bng khong 3% tc oxi ho ethanol. Cu trc ca ADH s l gii cho
s khc nhau ny. Cc alcohol khi c ADH xc tc s lin kt vi enzyme ny hai
vng khc nhau, mt l vng lin kt vi nhm hydroxyl, vng cn li s lin kt vi
u k nc ca alcohol. Phn t methanol v ethanol u c mt nhm OH, nhng
ui hydrocarbon ca methanol ch c mt carbon nn lin kt vi vng k nc trn
ADH kh khn dn n vic chuyn ion H+ cho NAD+ cng chm chp, cui cng l
vn tc oxi ho ca methanol chm hn ethanol.
i lc ca enzyme ny vi alcohol kh ln. Tc loi cn bi ADH ca gan
mc in vivo cho thy ADH c kh nng m trch c ton b qu trnh chuyn
ho alcohol. Tuy nhin, c mt s yu t c kh nng nh hng, kim sot hot tnh
ca enzyme ny.
Yu t th nht l nng c cht: vic ung ru lin tc, tip nhn alcohol
nhiu, ban u, s lm tng hot tnh ca enzyme, nhng tng qu mc hoc ung
ru trong mt thi gian di s lm gim hot ca enzyme.
Yu t th hai l cc yu t lin quan n co-enzyme ca ADH, NAD +. Do
mng ty th khng thm c nucleotide nn vic chuyn NADH v dng hot ng
NAD+ c thc hin bi mt lot cc phn ng khc nhau gia bn trong ty th v t
bo cht. Nh vy, tc chuyn ho ny s nh hng n hm lng NAD +, t
s nh hng n kh nng oxy ho ethanol thnh acetaldehyde. Lng NADH trong
t bo cht tng s hn ch hot ng ca ADH, v ngc li.
Yu t th ba l nng cc sn phm, c th y l lng aldehyde. Lng
aldehyde ln c th c ch ngc enzyme ADH.
b. Catalase
V tr khu tr Catalase v tng hp H2O2 chnh l vn lm cho vic oxy ho
alcohol bng con ng ny rt hn ch. Catalase thng c tm thy peroxisome,
cn H2O2 c to ra bng vic oxy ho mt s hp cht ty th. S c mt ng thi
Catalase v H2O2 gan l rt thp nn s hn ch s oxy ho alcohol.
Nh trnh by, mi loi alcohol s ph hp vi mt loi enzyme hn hai loi
cn li. V catalase chnh l con ng oxy ho chnh ca methanol. Vai tr oxi ho
alcohol ca catalase gan rt thp, nhng kh cao no, ni thiu enzyme ADH.
c. H thng oxy ho ca ty th (cytochrome)
5

H thng ny ln u tin c pht hin khi cho chut ung ru trong mt thi
gian di. Ti cc t bo gan ca chut xut hin s tng sinh mng li ni cht trn
trong t bo cht. S tng sinh ny cng tng t nh s tng sinh p li khi c
th tip nhn qu liu cc loi thuc v cc cht c. Trong h thng oxy ho ny,
enzyme in hnh nht l cytochrome P450. Cytochrome l mt h cc enzyme cha
nhn heme l cc enzyme monooxygenase c kh nng oxy ho c ethanol,
methanol, cc steroids, acid bo hoc thm ch l benzene, acetone, Ngoi gan,
ngi ta cng tm thy h enzyme ny t bo no v phi.
im ng ch nht ca enzyme ny l kh nng thch ng ca n vi
methanol v ethanol. Hng s Km ca P450 cao hn ADH gp 10 ln i vi c cht l
ethanol, do vy m nng thp, ADH gan c kh nng xc tc cao hn P450 rt
nhiu. Tuy nhin, P450 vt tri hn so vi ADH nng alcohol cao.
Mt khc, c mt hn ch khi P450 hot ng mnh, l s xut hin ca cc
th h oxi hot ng nh l O2 , H2O2 v cc gc t do khc. Cc tc nhn ny chnh
l nguyn nhn lm tn thng n cc t bo c P450 m c thu np qu nhiu
alcohol.

Hnh 2: Qu trnh chuyn ho nhn heme ca cytochrome sinh ra cc hp cht c

2.2 S chuyn ha acetaldehyde v cc hp cht gy c

Acetaldehyde, sn phm ca qu trnh oxy ha ru l mt cht c, nn sau khi
hnh thnh chng thng c chuyn ha ngay. Qu trnh oxy ha ny c xc tc
bi aldehyde dehydrogenase c coenzyme NAD+. Ngoi ra cn c aldehyde oxydase
v xanthin oxydase cng c kh nng phn hy acetaldehyde. Tuy nhin, qu trnh
phn hy acetaldehyde t ru ca hai enzyme ny thng khng hiu qu [5].
Phn ng ca aldehyde dehydrogenase c biu din nh sau:
Acetaldehyde + NAD+ + H2O2 acid acetic + NADH + H+
Enzyme ny khu tr gan cng nh hu khp cc m. Enzyme cha 4 di n
v, c khi lng phn t khong 200000. Da vo gi tr ca Km vi c cht, ngi ta
c th chia enzyme lm hai loi, loi enzyme c Km thp khong vi M v loi
enzyme c Km cao vi mM.
Bnh thng nng acetaldehyde lun rt thp. Khi ch c enzyme AldDH
vi Km thp mi hot ng c trong iu kin bo ha c cht nn c tc cao.
Cn enzyme AldDH vi Km cao th khng my c ngha i vi s chuyn ha
acetaldehyde t ra l trong iu kin bnh thng. Enzyme AldDH vi Km thp thng
c nh v ch yu trong ty th, do vy acetaldehyde c to ra do ADH trong
bo tng phi c vn chuyn qua mng ty th trc khi chng c oxy ha [5].
Cch thc chuyn ha acetaldehyde gi mt v tr rt quan trng v n lin quan
ti c tnh vn c ca thnh phn ny v c th c tnh c ca ru. Gan l c quan
ch yu chuyn ha ru do vy n cng chnh l ni chuyn ha acetaldehyde. Qu
vy nhiu nghin cu cho thy rt t acetaldehyde c to thnh trong gan thot khi
s chuyn ha ca AldDH, ngay c trong trng hp qu trnh oxy ha ru xy ra
mnh m, gan cng chuyn ha c trn 95% acetaldehyde to thnh, m bo duy
tr nng acetaldehyde trong mu tnh mnh khng bao gi vt qu 1-5M.
Enzyme ny hot ng ph thuc vo NAD+ v vo NADH do n to ra, nn dn
n lm gim hot tnh ca enzyme ADH nh cp trn. Ch c mt im khc
bit l NADH c to ra ch yu trong ty th, do qu trnh ti oxy ha chng
theo l thuyt c th d dng hn so vi lng t bo cht. Tuy nhin, theo nh lut
tc dng khi lng, NADH c to thm t con ng ny cng s gp phn lm
chm s chuyn vn ca NADH c sinh ra t qu trnh oxy ha ru trong t bo
cht [6].
7

2.3 Qu trnh oxy ha acetic acid v cc hp cht gy c trong chu trnh Krebs
Acid acetic c to thnh s tip tc c chuyn ha nh cc phc h enzyme
ca chu trnh Krebs to ra sn phm cui cng l CO2 v H2O kt hp vi vic tch
ly nng lng. Thc t, sau khi ung ru cc kt qu o nhit lng cho thy vic
s dng nng lng t glucid hoc t lipid. V mt ny, ng trn quan im dinh
dng ru cng c th c coi l mt cht dinh dng tt, bi n c kh nng to ra
khong 29kJ/g. Nu kh nng oxy ha ru l 100mg/kg/h th mt ngy m mi
ngi c th s dng 160g ru (ng vi khong 2 lt ru vang) to ra 4,5MJ
tng ng vi 2/3 nng lng to ra t qu trnh trao i cht c bn. Tuy nhin,
vic tnh ton ny ch thun ty v mt ton hc, trn thc t qu trnh chuyn ha ny
khng th din ra vi mt lng ln nh vy v n cn chu tc ng ca yu t dc
l khc [7].
Thc t, khi s dng mt lng ln ru thng rt hay dn n tnh trng tha
nng lng. Cc ung c ru thng cha rt t hoc khng c ng, khng c
protein nhng ru li thng kch thch ngon ming, n ung nhiu ln, gy tha
nng lng v dn n bo ph. Ngc li, mt vi yu t sinh l v tm l xut hin
ngi ung ru li dn n hin tng chn n hoc n ung tht thng dn n
vic gim kh nng hp th nit v vitamin gy ri lon tiu ha v suy gim dinh
dng [7].
3. S ri lon trao i cht do oxy ha ru
3.1 S chuyn ha ru trong c th
Ru c hp th vo mu qua cc mch mu nh ca thnh d dy v rut
non. Trong vng vi pht ung ru, ru di chuyn t d dy n no, ni nhanh
chng to ra cc hiu ng ca ru, lm hot ng ca t bo thn kinh chm li.
Khong 20% lng ru c hp thu qua d dy. Hu ht (80%) cn li c hp
th qua rut non.
Ru cng theo mu n gan, thi tr ru trong mu thng qua qu trnh ti gan
gi l chuyn ha, ni m ru c chuyn i thnh cht khng c hi. Gan ch
c th chuyn ha mt lng ru nht nh ti mt thi im, li lng d tha
lu hnh khp c th. Do , cng tc ng trn c th c lin quan trc tip n
8

s lng ru ung. Khi s lng ru trong mu vt qu mt mc nht nh, h

thng h hp (ht th) chm li r rt, v c th gy ra tnh trng hn m hoc t vong,
v thiu oxy no. Ru c chuyn ha hn 90% gan, cn li thi ra ngoi phi,
thn, da. Qu trnh chuyn ha ru gan gm 3 giai on:
Giai on 1: Chuyn ethanol thnh acetaldehyde qua 3 con ng chuyn ha:
Enzyme ADH (alcoholdehydrogenase) l con ng chnh > 80%, oxy
haethanol thng qua vic lm tng NADH dn n tng t l NADH/NAD+ ;
h thng microsome gan (MEOS): hot ng t khi nng ru thp v tng
hot ng khi nng ru cao v ngi nghin ru; h thng peroxidase
catalase: Tham gia rt t trong chuyn ha ethanol.
Giai on 2: Chuyn acetaldehyde thnh acetate nh enzyme ALDH
(Acetaldehyde dehydrogenase) cng thng qua vic bin NAD thnh NADH.
Giai on 3: Acetate thnh AcetylCoenzyme A a vo chu trnh Krebs chuyn
ha thnh CO2 v nc. Tc chuyn ha ca acetate trong chu trnh Krebs
ph thuc vo lng Thiamine trong mu.
nhng ngi lm dng ru, lng Acetaldehyde c sn sinh vi mt mc
qu ln s khng c chuyn ha ht v gn vo mng t bo gy tn thng t bo
thng qua cc c ch gy c, vim v min dch vi hu qu l qu trnh to x.
Nh vy nhng ngi ung mt lng ln ru th u tin khi nng cn
trong mu cao, h thng MEOS s hot ng. H thng Enzyme ny c tm thy
mng ca mng li ni bo tng nhn. Enzyme quan trng nht ca h thng ny l
Cytochrom P450 bi men ny khng ch c vai tr trung tm trong chuyn ha ru
m cn tham gia vo vic ging ha rt nhiu cht ca chnh c th cng nh cht l t
bn ngoi vo, v d rt nhiu loi thuc khc nhau thng c s dng trong lm
sng.
Cytochrom P450 2E1 (CYP 2E1), mt di type ca Cytochrom P450, c vai tr
quan trng nht trong chuyn ha Alcohol thnh Acetaldehyde. Vo nm 1968, ln u
tin Charles Lieber chng minh rng vic s dng thng xuyn thc ung c cn
9

s gy cm ng lm tng hot h thng men ny ln 10 ln. Mt c im cc k

quan trng l phn ng ging ha ny s gii phng ra cc gc xy t do hot ng
(reactive oxygen species ROS).
Enzyme Catalase trong Peroxisome ch tham gia oxy ha mt lng rt nh
Ethanol m thi. Vic thng xuyn s dng mt lng ln Alcohol s lm tng hot
ng ca hai enzyme khc na tham gia vo qu trnh chuyn Acetaldehyde thnh
Acetate. l cc men Xanthinoxidase v Aldehydoxidase. Thng qua hot ng ca
hai men ny, thm mt lng ln cc gc t do gy c c gii phng, gp phn to
nn nhng tn thng gan do ru.
Tm li, gan l c quan chc nng chnh gip chuyn ha ru, l nguyn
nhn ti sao ung nhiu ru c th dn n nhiu bnh ca gan. Ru c o thi
v loi b ra khi mu thng qua qu trnh oxy ha. Qu trnh oxy ha ny gip ngn
cn ru tch ly trong c th gy ph hy cc t bo v ni tng. Cc t bo gan ch
c th x l mt s lng ru nht nh mi gi. Mt l gan khe mnh c th oxy
ha ru tinh khit t l n ca 30ml ru trong 1 gi, ngha l trong 1 gi
gan ch c th oxy ha c t hn 30ml ru mnh. V vy, nu ung ru nhiu hn
mc x l ca gan, ru trong mu tng ln.
3.2 Ri lon trao i cht do oxy ha ru
Hot ng ca hai enzyme ADH v AlDH khi oxy ha ru trong t bo lm
tng ng k t l NADH/NAD+. c bit l t bo cht, ni sinh ra cc NADH (bi
ADH) nhng kh nng ti oxy ha NADH y li khng hiu qu do lm cho
lng NAD+ nhanh chng b thiu ht dn n km hm mt vi ng hng chuyn
ha ph thuc NAD+. Cng nh vy ty th, NAD+ c u tin s dng cho qu
trnh chuyn ha acetaldehyde v chu trnh Krebs khi b km hm bi t l CO2/O2
gim. Do vy, khi qu trnh oxy ha ru tr thnh u th hn n s s dng khong
60 80% lng oxy ca gan nn s lm gim kh nng oxy ha cc c cht khc. Tuy
nhin, ngoi kh nng sn sang ca cc cofactor qu trnh chuyn ha etanol cng nh
cc c cht cung cp nng lng khc u ph thuc vo nhu cu nng lng ca t
bo hay ni cch khc ph thuc vo t l ATP/ADP.

10

Thc t, tc do thi ru ph thuc vo qu trnh trao i cht c bn v kh

nng s dng oxy. V vy, mi con ng l tng kh nng ny u thc y qu trnh
o thi ru. C mt c ch tng nhanh s chuyn ha ru do Thurman ra, khi
lng ru c a vo c th ch duy nht mt ln nhng liu cao (5g/kg th
trng) th lng oxy tiu th gan s tng ln gp i. Tham gia vo trong c ch ny
c s hot ng ca chui vn chuyn electron v enzyme ADH. im khi u ca
c ch l hiu ng h nhit ca ru s kch thch s tit ra cc hormone adrenalin v
noradrenalin. Adrenalin s hot ha ATPase dn ti tng nhu cu oxy. Nhiu thc
nghim khc chng t c ch ny ni lin vi qu trnh trao i cc glucid theo hai
cch: Hoc l ngun glycogen b cn kit do hormone kch thch hoc l qu trnh
ng phn b phong b do trng thi oxy ha kh ca t bo cht. Trong c hai
trng hp s ng phn u b dng li, ADP ca t ba cht s tch t ri chuyn
qua mng ty th ti chui phosphoryl ha thc y qu trnh tiu th oxy.
a. S gim oxy huyt v hoi t gan
Nhu cu oxy tng lm tng s chnh lch p sut ring phn ca oxy gia cc
tnh mch ca v tnh mch gan dn ti vic thiu oxy trong mu. Thc nghim vi
cc m gan ng vt x l vi ethanol v trong iu kin thiu oxy (thiu mu, h
hp km) thy xut hin cc thng tn, hoi t v nhim m. Hin cha c nhng kt
lun chnh xc v vic thiu oxy tng i cc tnh mch ngoi vi l nguyn nhn
gy ra s hoi t gan. Tuy nhin, vic thiu ht oxy bi qu trnh trao i cht ny
ngi ung ru thng lm tng cng mt s triu chng nh thiu mu, ri lon
h hp, d nhim c thuc, gim th tch huyt cu, au c tim.
b. Qu trnh collagen v s ha x
Ung ru lu ngy cng s gy chng ha x gan do qu trnh trao i collagen
b ph hng. Chng ha x ny i khi lm tc cc tnh mch nh ca gan lm trm
trng thm tnh trng thiu ht oxy huyt v suy dinh dng. S thiu oxy v to ra
acid lactic do qu trnh trao i ru li l nhng cht hot ha enzyme collagen prolin
hydroxylase. Enzyme ny thng c mt trong nguyn bo si do c th dn n
lm tng thnh phn hydroxylprolin trong collagen. Cc nghin cu lm sng ch ra
c mi quan h gia hot ng ca collagenprolin hydroxylase vi t l x ha trn
cc sinh thit.
c. Chng to ty th
11

Mt trong nhng ch tn cng ca ru vo t bo gan l ty th. Trn phng

din hnh thi hc nhng ngi ung ru lu nm thng c s tng ln v kch
thc ca ty th. Thc nghim in vitro cho thy ru lm h hng mt s chc nng
ca ty th thng qua vic lm tng tnh thm ca mng ty th. Trong mu ca mt s
ngi nghin ru thy xut hin glutamadehyrogenase, mt enzyme thng ch nh
v trong ty th. Hn na, vic s dng ru s lm cho ty th tr nn mng manh, lc
u ty th b phng ln v sau lp bn ngoi b ph v. S sinh bnh t hin tng
ny l c lin quan vi cu trc lp mng lipid b ph hy do sn sinh thm lipase hoc
do hot ha cc phospholipase ni sinh.

d. S nhim m
Mt trong nhng bnh v gan quen thuc ca ngi nghin ru l s nhim m.
Hin tng ny l kt qu tng tc ca ethanol vi cc qu trnh trao i lipid v
lipoprotein.
L tnh trng cc ht m tch t trong t bo gan chim trn 5% trng lng gan
v lm hn ch hot ng ca t bo gan
L biu hin sm ca bnh gan do ru, thng him khi c triu chng, i
khi thy mt mi, y hi, kh tiu, nng tc vng h sn phi, nng hn c
th thy vng da, bun nn, nn hay s thy gan to.
Cc xt nghim sinh ha mu nh men gan u bnh thng hoc tng nh.
Siu m l phng php chn on tng i chnh xc, sinh thit gan s gip
phn bit vi nguyn nhn khc.
Gan nhim m tuy lnh tnh, nhng t l pht sinh x ha cao
Chng ta u bit cung cp nng lng cho c th, ty th phi dng cc cht
nh NADH2 t qu trnh oxy ha ru v acetaldehyde c bit l cc cht kh ca
chu trnh Krebs khi oxy ha cc cu t hai carbon vn c phn ct ra t acid bo.

12

Khi c ru, chng s thay th cc acid bo lm ngun cung cp nng lng chnh cho
t bo. Vic gim oxy ha cc acid bo s dn n s tch t m gan.
Vic tng t l NADH/NAD+ cng lm tng s tch t lng glyceraldehyde 3
phosphate trong gan. T cht ny d dng ester ha vi cc acid bo t do to
thnh triglycerid.
4. Dc hc v c tnh ca acetaldehyde v cc hp cht gy c [6, 7, 8]
Phn ln lng ru ung vo c hp th vo mu v chuyn ha gan (85
ti 98%), mt s nh c thi trc tip qua phi hoc thn (2 ti 10%), hoc c
hp th v chuyn ha khu tr ti cc t bo tit nhy d dy (0 ti 5%). Chng ta
ch xt con ng chuyn ha quan trng ti gan, ni y din ra hai qu trnh khc
nhau p ng vi lng ru v thi gian ung ru khc nhau, cui cng gii phng
cc mc nng lng khc nhau dn n kt qu chnh l nghch l trong thc t. C 2
con ng chuyn ha ru thnh acetaldehyde.
Con ng chuyn ha th nht: thng qua hai h thng men ADH (alcohol
dehydrogenase) v ALDH (acetaldehyde dehydrogenase). y l con ng
chnh xy ra nhng ngi ung ru va phi. Sn phm cui cng l acetate,
theo mu n tiu th m c. Ton b con ng ny gii phng nng lng
xp x 7 kcal/gram ru nguyn cht. S chuyn ha tun theo ng hc bc 0,
ngha l mt khi lng c nh c chuyn ha trong mt n v thi gian.
Ngi ln khng nghin chuyn ha khong 7-10g ethanol mt gi vi s gim
dn nng ethanol trong mu xp x 15-20mg/dL/gi. Ngi nghin ru
hoc ung qu nhiu ru c th chuyn ha nhanh hn v nng ethanol
trong mu c th gim vi tc 30-40mg/dL/gi. Ethanol c chuyn ha
ch yu bi ng alcohol dehydrogenase bo tng ca t bo gan:
Ethanol + NAD+Acetaldehyde + NADH + H+
Alcohol Dehydrogenase
Acetaldehyde + H2O + NAD+Acetate + NADH + H+
Alcohol Dehydrogenase
Acetate AcetylCoA CO2+ H2O
Chu trnh Krebs
13

 Con ng chuyn ha th hai: thng qua h thng men MEOS (microsomal

ethanol oxidizing system) v ALDH. Con ng ny thng thng ch chuyn
ha 10% ti 20% lng ru ung vo mt ngi ung va phi. Khi ung
ru ko di, c th ta s p ng chng chi bng cch tng gp 5 ti 10 ln
h thng MEOS ln, gip thi tr ru nhanh hn ngi bnh thng. Chnh v
s dng MEOS tht ra li tiu tn nng lng (ngc li vi ADH con ng
th nht l gii phng nng lng) nn ngi ung ru ko di, ru mt
vai tr l cht cung cp nng lng..

Hnh 3: Con ng chuyn ha ru thnh acetaldehyde

Khi ung ru nhiu v lu di, mc MEOS tng ln nhiu nhng ALDH li
khng tng, dn n tch t acetaldehyde, mt trong nhng yu t gy bnh l ti gan.
Ru cha cht ethanol. Khi ung ru, c th chng ta tip thu cht ethanol, v tri
qua hai bc chuyn ha trong gan. Bc th nht, enzyme ADH chuyn ha ethanol
thnh acetaldehyde. Bc th hai, enzyme ALDH2 chuyn ha acetaldehyde thnh
acetate l acid axetic m chng ta thy trong gim. Trong ba hot cht (ethanol,
acetaldehyde v acetate), acetaldehyde c xem l c hi nht, v n c kh nng
gy c 30 ln so vi ru, gy t bin DNA v ung th. Mc c hi ca
ethanol thng thp, v acetate th tng i v hi. Khi acetaldehyde tch t trong
mu s gy ra tnh trng nng bng, bun nn v nn v mt s ngi th nhp tim
p nhanh khi ung ru. Chnh acetaldehyde cng l nguyn nhn ca nhng d
hng nh nhc u vo bui sng sau khi ung ru trong m trc.
Nhiu nghin cu trong vng 2 thp nin qua cung cp cho chng ta nhiu thng
tin quan trng v nh hng ca gen n tu lng ca tng c nhn. Qu trnh
chuyn ha t ethanol trong ru sang acetaldehyde chu s iu phi ca mt gen c

14

cng tn vi enzyme l ALDH. Gen ALDH c hai phin bn l Glu (tm vit tt l G)
v Lys (L); do , trong dn s c 3 nhm ngi vi 3 bin th gien: GG, LG v LL.
Ngi mang bin th LL c th khng c kh nng chuyn ha acetaldehyde mt
cch hu hiu, v do hot cht ny tch t trong c th. Chnh v l do ny m
ngi mang bin th LL khi ung ru mt tr nn ng, hay i ma, v tim p
nhanh. Bin th LL hin din trong khong 30-40% ngi ng (Nht, Hn
Quc, Trung Quc).
Ngi mang bin th LG c kh nng chuyn ha acetaldehyde tt, nn h c
tu lng cao hn nhng ngi vi bin th LL. Phn ln nhng ngi ung ru
nhiu Nht v Hn Quc mang trong mnh bin th LG v GG.
Nhng nguy c ung th ty thuc vo bin th gen. i vi nhng ngi ung
ru, ngi mang bin th LL c nguy c ung th cao hn ngi mang bin th LG v
GG. Chng hn nh nu ngi mang bin th LL m ung nhiu ru (trn 400 mg
mi tun) nguy c ung th thc qun tng gp 50 ln so vi ngi cng mang bin th
LL hay LG ung ru vi liu lng thp (di 200 mg ethanol mi tun). Tuy nhin,
v nhng bin chng bun nn, nn v nng bng, nn ngi mang bin th LL
thng khng ung nhiu ru. Do , ung th thc qun hay thy nhng ngi
mang bin th LG v GG. Tht vy, nghin cu Nht cho thy khong 60-70%
trng hp ung th thc qun l do bin th LG
S kch ng thn kinh c th gy ra bi Ethanol c th dn dn vic sao chp
gen, dch m protein sai hoc ri lon mt s h thn kinh dn truyn. Ngoi nhng tc
ng trc tip ca ru ethanol ln h thn kinh trung ng v cc chuyn ha sinh hc
th acetaldehyde c to ra bi qu trinh thy phn ru bng cc enzyme
dehydrogenase. Acetaldehyde lm gim s lu thng ca cc cht qua mng t bo v
lm ri lon chc nng ca cc protein vn chuyn qua mng. Ngoi ra acetaldehyde
cn c coi l mt cht ha hc tng t nh formaldehyde c kh nng gy ung th,
ph hy DNA, kch thch s pht trin, sn sinh ra cc t bo c tnh rn c th.
Acetaldehyde c th tc ng trc tip lm ph v cu trc thng thng trn DNA s
nh vi cc DNA ngi to thnh cc DNA adduct (DNA cng sinh) gy ra cc
t bin nhim sc th ca t bo. Cc DNA cng sinh s tng tc vi ADN bnh
thng v lm nhiu lon hot ng ca chng. Mc d c th ngi c c ch sa
cha nhng sai lnh trn cc DNA cng sinh, tuy nhin vic s dng ung c cn
15

qu mc s lm qu trnh ny tr nn v ngha. Hu qu tt yu l ngi ung i mt

vi nguy c cao b ung th
Sau khi ung mt lng ln ru, nhiu ngi thng c cm gic kht v tin
rng sau khi ung ru ngi ta c cm gic kht nc. Vic li tiu c th do ruethanol mang li, iu ny c gii thch l do Ethanol lm c ch hocmon
Vasopressin (Vasopressin l mt hormon polypeptid ca thy sau tuyn yn, c tc
dng trc tip chng li tiu, nn c gi l hormon chng bi niu. Vai tr sinh l
ch yu ca vasopressin l duy tr thm thu ca huyt thanh trong phm vi bnh
thng. Vasopressin lm cho nc tiu c c tng i bng cch tng ti hp thu
nc ng thn) dn n s gia tng hnh thnh nc tiu. Tuy nhin, cm gc li tiu
ny do liu lng nc tiu bi tit thp ch khng phi do th tch ru ethanol ung
c. iu ny cho thy li tiu khng phi l yu t gy ra kht cm gic sau khi
ung nhiu ru Ethanol. Trong nghin cu in vivo v in vitro ch ra rng
acetaldehyde cng tc ng ln h thn kinh v no vt qua c hng ro mu no nn
cc acetaldehyde c th tc ng trc tip vo h thn kinh v gy ra cm gic kht.
Khi ung ru ethanol ngi ta cn c cc triu chng khc ngoi kht l cm
gic nn nao, bun nn, cc triu chng ny c cho l gy ra bi acetaldehyde. Tuy
nhin, acetaldehyde khng c coi l tc nhn gy l cn kht sau khi ung ru v
n khng c c ch hocmon Vasopressin m n lm gin cc mch mu v lm gim
huyt p. Acetaldehyde c ch tit renin t thn, dn n gia tng nng angiotensin.
H renin-angiotensin l mt h thng cc hormon lm nhim v iu ha cn bng
huyt p v dch ngoi bo trong c th ngi. Khi th tch mu trong c th ngi h
thp khin huyt p gim, thn s tit renin kch thch s sn sinh angiotensin.
Angiotensin gy co mch mu dn n vic tng huyt p. Angiotensin cng c ch
hormon aldosterone t lp cu v thng thn. Aldosterone lm tng ti hp thu nc
v ion Na+ cc t bo biu m ng thn. iu s dn ti vic tng lng nc
trong c th, phc hi huyt p.
Hnh 4: H renin-angiotensin

16

5.

nh hng ca acetate
Qu trnh bin i acetat thnh acetyl CoA lm tng cng chuyn ha ATP
thnh AMP. Nhu cu tiu th ATP ny c th gy c cho gan v gy ra tnh trng tng
chuyn ha gan u l kt qu ca vic dng nhiu ru.

Hnh 5: Tc ng acetate n gan

Gan l c quan chuyn ha ru quan trng nht. Trn 90% lng ru hp thu
s c chuyn ha ti gan, phn cn li s c thi ra ngoi qua phi v thn.
Ti gan, ru s c chuyn ha thnh Acetalhehyde l mt cht c, sau
chuyn thnh Acetate khng c. Tuy nhin, kh nng chuyn ha Acetalhehyde thnh
Acetate ca gan li c gii hn. Nu hp thu lng ru qu ln vt kh nng chuyn
17

ha ca gan dn n lng Acetaldehyde c sn sinh vi mt mc qu ln s dn

n tnh trng tn thng t bo gan, gy tnh trng vim gan, x gan.
Trong giai on 1, chuyn ha ru thnh Acetalhehyde c thc hin bi ba h
thng men: (1) Alcoholdehydrogenase (coenzyme NAD) nm trong bo tng; (2) h
thng xy ha ru microsome (Microsomal Ethanol Oxidating System MEOS) v
(3) cc men Catalase. Tuy nhin ngi ung ru nhiu th h thng men MEOS c
tm quan trng hn ADH.
Trong giai on 2, acetaldehyde uc hnh thnh, l mt cht c, s nhanh
chng c xy ha chuyn thnh Acetate. Nng lc chuyn ha ca giai on ny
ch c gii hn v c s tham gia ca ADH, mt enzyme ph thuc NAD. nhng
ngi lm dng ru, lng Acetaldehyde c sn sinh vi mt mc qu ln s
khng c chuyn ha ht v gn vo mng t bo gy tn thng t bo thng qua
cc c ch gy c, vim v min dch vi hu qu l qu trnh to x.
Nh vy nhng ngi ung mt lng ln ru th u tin khi nng cn
trong mu cao, h thng MEOS s hot ng. H thng Enzyme ny c tm thy
mng ca mng li ni bo tng nhn. Enzyme quan trng nht ca h thng ny l
Cytochrom P450 bi men ny khng ch c vai tr trung tm trong chuyn ha ru
m cn tham gia vo vic ging ha rt nhiu cht ca chnh c th cng nh cht l t
bn ngoi vo, v d rt nhiu loi thuc khc nhau thng c s dng trong lm
sng.
Cytochrom P450 2E1 (CYP 2E1), mt di type ca Cytochrom P450, c vai tr
quan trng nht trong chuyn ha Alcohol thnh Acetaldehyde. Vo nm 1968, ln u
tin Charles Lieber chng minh rng vic s dng thng xuyn thc ung c cn
s gy cm ng lm tng hot h thng men ny ln 10 ln. Mt c im cc k
quan trng l phn ng ging ha ny s gii phng ra cc gc xy t do hot ng
(reactive oxygen species-ROS).
Enzyme Catalase trong Peroxisome ch tham gia xy ha mt lng rt nh
Ethanol m thi.
Vic thng xuyn s dng mt lng ln Alcohol s lm tng hot ng ca hai
enzyme khc na tham gia vo qu trnh chuyn Acetaldehyde thnh Acetate. l
cc men Xanthinoxidase v Aldehydoxidase. Thng qua hot ng ca hai men ny,

18

thm mt lng ln cc gc t do gy c c gii phng, gp phn to nn nhng

tn thng gan do ru.
6. nh hng ca ethanol ln mng t bo
Ri lon trao i cht do etanol gy ra lin quan n mt s bnh l nh ri lon
trao i lipid gan i km vi bnh gan nhim m, thay i th oxi ha kh t bo
th gy hoi t gan. Nguyn nhn l do phn t etanol c kh nng khuch tn trong
mi trng phn cc ln khng phn cc, t n lan nhanh ra ton c th. Chnh
iu ny lm cho phn t etanol ha tan c vo nhng vng k nc ca mng sinh
hc (mng phospholipid kp) to ra trng thi cn bng mi gia 2 pha mng. T ,
chng can thip vo qu trnh trao i cht bn trong mng v qu trnh vn chuyn
cc cht qua mng. V d, s bin i cu trc mng ty th l nguyn nhn dn n
thay i chc nng ca ty th.

Hnh 6: Phn t etanol y cc phn t lipid v ph v s sp xp ca chng.

6.1 nh hng ha l ca ru ln mng t bo
Ru c th gy t vi mng t bo. L do s ha tan ca ru vo vng lipid
ca mng t bo dn n ngn cn s truyn tn hiu thn kinh.
Hu ht cc nh hng ca ru ln cu trc v chc nng ca mng t bo u
da trn kh nng h tan ca chng v mng t bo. Mt s thc nghim cho thy s
gn hoc hp th cc ru no ln mt s cu trc lipid khc nhau thng do cc
receptor c hiu m nhn. S gn kt ny lm tng din tch b mt mng v gy
xo trn s sp xp lp lipid mng. Qa trnh ny c thit lp dn dn v to ra tnh
chng chu cho php mng t bo bn vi nhng xo trn mnh gy ra bi ru. Sau
19

thi gian thch nghi di, mng t bo s bin i v nu nh vng ru chng s khng
thc hin c chc nng ca minh. Do , trong thi gian cai ru c th xut hin
mt vi ri lon chc nng ngc vi nhng ri lon ban u do ru gy ra.

Hnh 7: Mt receptor ca protein mng cho hp thu etanol

6.2 nh hng ti cc thnh phn ha hc ca mng t bo
S thch ng vi trng thi say ru lu ngy cho thy t l
cholesterol/phospholipid dng nh tng ln cn lng axit bo khng no ca
phospholipid mng t bo li b gim xung.
Rt kh nh gi c vi tr ca cholesterol vi cu trc mng bi l cc mng
thng rt giu cholesterol v nu nh cc mng chng chu c tc dng lm tan r
ru th s khng c nhng thay i c bn v cu trc. Mt khc, lng ca mng
t bo li thng c lin quan vi nhng mng giu cholesterol
Ru thng gy hin tng no ha vi cc axit bo. Ru lm gim s lng
cc lin kt i v i khi lm tng mt s axit bo no khng bo ha mt ni i. S
tng loi axit bo 18:1 li i km vi s gim loi 18:2, dn n lm mng t bo ha
cng. Tuy nhin, hin tng n li kh thy cc loi mng c lng axit bo thp.
Ru cn c nhng tc ng n s tng hp v s t chc ca cc lipid mng
cng nh s tng hp v hnh th cc protein mng. Etanol tng tc vi cc cu trc
mng t bo theo hng lm cho chng thch nghi c vi cc tc ng lin tc ca
ru trong nhng chu k tim ngm ru ko di.
Hnh 8: Tc ng ca ru ln mng t bo
20

6.3

C
c

hu qu chc nng ca s thch ng ca mng t bo

Qu trnh vn chuyn ion natri v kali qua mng cho thy n c vai tr quan
trng trong vic to ra in th mng. Khi enzyme b km hm s lm tng qu trnh
vn chuyn ion. C th s km hm enzyme l do tc ng trc tip ca etanol n
phn protein ca enzyme trong khi s hot ha vic vn chuyn ion li do cc bin i
hnh th thng qua mi trng lipid.
Qu trnh trao i canxi c bit cc im nt thn kinh b nh hng bi
etanol. Nu s dng mt liu duy nht etanol s gy ra hin tng gim canxi mng,
ngc li u s dng cc liu lp li s lm tang hm lng canxi. Mi lin kt ca
canxin vi mng t bo ph thuc vo cc axit bo v lin quan n lng ca mng.
Canxi c ngng kt vo u phn cc ca phospholipid v do s c nh c
cc i phn t tch in m khc. Khi lm lng canxi mng tng s lm tng rn
chc ca mng. Vic tng hm lng canxi l nguyn nhn gy ri lon qu trnh trao
i cc base ca cc phospholipid c c ch ph thuc canxi, kt qu s lm thay i
thnh phn lp phospholipid mng.
Cc nucleotide vng tham gia vo cc qu trnh mng ca cc receptor v kh
nng thm ion mng cng b tc ng ca etanol. Chng hn khi x l ko di bng
etanol s lm tng hm lng AMP vng trong no ng thi li lm gim lng GMP
21

vng mt vi vng c bit h tiu no, v thng thn (cortex). Thng t s nng
ca GMP vng v ca GABA (axit gama amino butyric) s quyt nh cho s biu
hin ca hi chng cai ru.
Ethanol gn trc tip vi cc receptor ca axit gama-amino butyric gy ra hiu
ng gim au tng t nh ca benzodiazepine.

TI LIU THAM KHO

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gastroenterology, 26(1), 3-15.
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absorption, gastric emptying and a breathalyser. British journal of clinical
pharmacology, 9(2), 205-208.
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3 L Ngc T, c t hc v an ton thc phm, NXB Khoa hc v k thut,

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Manchilha, I. M. (1995). Effect of acetic acid on xylose fermentation to xylitol
by Candida guilliermondii. Journal of basic microbiology, 35(3), 171-177.
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(2015) 589-599, Izumi Ujihara, Suzuro Hitomi, Kentaro Ono, Yasuaki
Kakinoki, Hirofumi Hashimoto, Yoichi Ueta, Kiyotoshi Inenaga.
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in Vitro 28 (2014) 822828, Kamila Cagliari Zenki, Ben Hur Marins Mussulin,
Eduardo Pacheco Rico, Diogo Lsch de Oliveira, Denis Broock Rosemberg
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