Bai giang

HOA HOC HEMOGLOBIN

ThS. Tran Th Tng Linh

oi tng giang: Lp D3 & CT2

MUC TIEU

1.Mo ta c cau tao hoa hoc, cach phan loai & tnh
chat cua Porphyrin
2. Mo ta c cau tao hoa hoc cua Hem va Globin
3. Trnh bay, giai thch c s ket hp gia Hem va
Globin.

4. Neu c tnh chat hoa hoc va vai tro quan trong cua
Hemoglobin trong c the

AI CNG

Cromoprotein
Protein phc tap co nhom ngoai la chat mau
- Cromoprotein vi nhom ngoai khong cha nhan porphyrin.
Flavoprotein : nhom ngoai cha riboflavin
Feritin : nhom ngoai cha Fe
Hemocyamin : nhom ngoai cha Cu
- Cromoprotein vi nhom ngoai cha nhan porphyrin (porphyrinoprotein)
Hemoglobin : sac to o cua hong cau.
Myoglobin: sac to ho hap trong tb c
Clorophyl: diep luc to
Cytocrom: tham gia phan ng oxy hoa kh trong chuoi ho hap tb
Catalase :tham gia phan ng oxy hoa kh sinh hoc

AI CNG

Porphyrin
Cau tao hoa hoc: Nhan porphin + nhom the
Porphin:
- 4 vong pyrol lien ket qua 4 cau noi methylen (- CH=).
- Cac vong pyrol c anh so I, II, III va IV (chieu kim ong ho)

- Cac cau noi methylen c ky hieu , , , .

-V tr cua cac nhom the tren khung phan t c anh so

1, 2, 3, 4, 5, 6, 7 va 8.

CH

CH

CH

CH
NH

NH

Vong pyrol

(1)

(2)

HC

CH
I

HC

CH

(8) HC

CH (3)

(7) HC

CH (4)

NH

III

HC

CH

(6)

(5)

8
7

III
6

3
II

CH

IV

HN
4

HC

HN II

IV NH

Porphin (dang viet tat)

Porphin

Cau truc nhan porphin

Porphyrin
La nhan porphin c gan them cac nhom the

Nhom the
Ten goc

Cong thc

Ky hieu

Metyl

-CH3

Etyl

-CH2 - CH3

Hydroxyetyl

-CH2 - CH2 - OH

E -OH

Vinyl

-CH= CH2

Acetyl

-CH2 - COOH

Propionyl

-CH2 - CH2 - COOH

Mot so dan xuat porphyrin thng gap trong t nhien

NH

P
NH

HN

Protoporphyrin IX (III)

NH

Coproporphyrin I

M
HN
P

N
P

P
N

HN

N
P

Coproporphyrin III

Mot so dan xuat porphyrin thng gap trong t nhien

P
N

A
NH

A
HN

NH

Uroporphyrin III

A
P

N
A

Uroporphyrin I

N
HN

NH

HN

E- OH

P
Hematoporphyrin

E- OH

Porphyrin
Tnh chat
- Co mau , co pho hap thu ac trng
- o tan phu thuoc so lng nhom carboxyl the.
V du: Uroporphyrin co 8 nhom carboxyl nen tan rat tot trong nc
Protoporphyrin co 2 nhom carboxyl nen t tan trong nc, tan
nhieu trong lipid.
- De tao phc vi ion kim loai

Metaloprotein

Hemoglobin, myoglobin, cytocrom, catalase: porphyrin + Fe2+.

Clorophyl: porphyrin + Mg2+
- Tnh kiem yeu (N cua nhan pyrol) va tnh acid (-COOH mach nhanh).

iem ang ien: 3 - 4,5.

HEMOGLOBIN (Hb)
ai cng
- Huyet cau to hay huyet sac to, ky hieu: Hb
- Cromoprotein (porphyrinoprotein), mau o, co / hong cau
ong vat cao cap.
- Ket tinh di dang nhng tinh the khac nhau tuy theo loai
ong vat

- Hong cau ngi cha 32% Hb (15g/ 100 ml mau).

Cau tao Hb
- Protein thuan: Globin
- Nhom ngoai: Hem.
Hem
- Nhan protoporphyrin IX + sat hoa tr II (Fe2+).
- Fe2+ trung tam noi vi 4 N cua bon vong pyrol qua 4
lk nam tren mat phang (2 lk cong hoa tr va 2 lk phoi tr)
V

M
N

Fe

M
N

P
HEM

Hem
- Hem b oxy hoa thanh hematin (Fe2+ bien thanh Fe3+).
- Hematin ket tinh dang muoi tinh the clorhydrat ac
biet (tinh the Hemin hay Teichman).
ng dung: xac nh vet mau trong phap y.

Fe OH
N

Hematin

Fe Cl
N

Hemin

Globin
Cau truc bac 1
Globin cua Hb A1 gom 4 chuoi polypeptid :
- Hai chuoi (141 aa/chuoi)
- Hai chuoi (146 aa/chuoi).
TC: 574 acid amin.
To hp chuoi: 2 2

Cau truc bac 2

- 80% aa cua cac chuoi va tao nen: 7 oan xoan helix (chuoi
) hay 8 oan xoan helix (chuoi ).
- Moi oan xoan gom 7 - 20 aa, ky hieu A, B, C ..theo th t
- Nhng oan aa con lai khong xoan, nam gia noi cac oan xoan,
ky hieu bi hai mau t cua hai oan xoan hai ben.
(v du: gia oan xoan A va oan xoan B la oan AB khong
xoan)

Globin

Cau truc bac 3

- Cac chuoi va cuon khuc tai cac oan acid amin

khong xoan
- Moi chuoi polypeptid xoan va cuon khuc + Hem = tieu
n v cua Hb.

Cau truc bac 4

Bon tieu n v ket hp vi nhau tao thanh mot phan t

Hb co cau truc bac 4 (tetramer)

S ket hp gia Hem va Globin tao Hemoglobin

1 chuoi polypeptid cua Globin + 1 Hem:
- qua lien ket phoi tr gia Fe2+ cua Hem vi nit (N) trong
nhan imidazol cua acid amin histidin oan xoan F8 (His
F8 hay His gan) va oan xoan E7 (His E7 hay His xa) cua
moi chuoi globin.
Hai lk nay ve hai pha cua mat phang protoporphyrin
- tao thanh mot tieu n v (subunit) cua phan t Hb.
1 Globin + 4 Hem = 1Hb
Hemoglobin gom 4 tieu n v (tetramer)
(moi tieu n v gom 1 chuoi polypeptid + 1 hem)

S ket hp gia Hem va Globin tao Hemoglobin

V
I

IV N

Fe

II

V
HEM
M

GLOBIN

HEM
GLOBIN

III
N

HEM

HEM

S ket hp gia Hem va Globin tao Hemoglobin

Cau truc bac 4 cua Hemoglobin

S ket hp gia Hem va Globin tao Hemoglobin

Cau truc bac 4 cua Hemoglobin

Cac loai Hemoglobin

- Globin quyet nh ac tnh chung loai cua Hb.
- Cac globin khac nhau do thanh phan & th t sap xep
cua cac a.a khac nhau lam thay oi cau truc va tnh chat
cua Hb.

Hemoglobin bnh thng

- Hb G (Gower) 2 2 , (bao thai).

- Hb P (Porland) 2 2 (bao thai).
- Hb F (Fetal): 2 2 (tre s sinh)
- Hb A1 (Adult): 2 2 (ngi trng thanh)
- Hb A2 (2,5% tong so Hb): 2 2 (ngi trng thanh)

Cac loai nay ch khac nhau oan xoan F cua globin.

Cac loai Hemoglobin

Chuoi
Polypeptid/
Hb

V tr xoan
F1

HbA ()
HbA2 ()
HbF ()

F2

F3

F4

Phe Ala Thr Leu

Phe Ser Gln Leu
Phe Ala Gln Leu

F5

F6

F7

F8

F9

Ser
Ser
Ser

Glu Leu His Cys

Glu Leu His Cys
Glu Leu His Cys

S khac nhau ve thanh phan aa cua HbA, HbA2, HbF tai cac
oan xoan

Hemoglobin bat thng (benh ly)

Nguyen nhan
S thay oi thanh phan va th t cua cac aa trong phan t
globin

Anh hng
- thay oi o tan va o ben vng cua Hb.
- anh hng en ai lc cua Hb oi vi oxy cung nh s
van chuyen oxy en cac to chc.
Hb bat thng gay benh ly

Hemoglobin bat thng (benh ly)

Hb S (2A 2S )
Glutamat v tr 6 cua chuoi c thay bang
valin,
hong cau co dang li liem.
Hong cau b pha huy gay benh ly thieu mau
tieu huyet man tnh, au keo dai, ot qu, suy
than.
Chan oan: ien di huyet thanh/OHHb S chuyen dch ve anod cham hn Hb A

Hemoglobin bat thng (benh ly)

Hb C (2A 2C)
- Glutamat v tr 6 cua chuoi c thay bang lysin.
- Hong cau co hnh bia.

Hb M:
Fe luon dang Fe3+ tao methemoglobin mau khong cha
c bang thuoc

Benh - Thalassemie
- Hb bart va Hb H : bat thng / tong hp chuoi polypeptid
- Gay benh thieu mau hong cau nho nhc sac .
Benh -Thalassemie
- ot bien/ tong hp chuoi , gay benh thieu mau.

- Xay ra chu yeu vung a trung hai

Tnh chat cua Hemoglobin

Ket hp vi O2 tao Oxyhemoglobin (HbO2).
Hb

HbO2

O2

oxyhemoglobin

Hemoglobin

ay la phan ng gan oxy hay s oxygen hoa ch khong

phai la phan ng oxy hoa v ion sat van con hoa tr 2.
M

V
I

IV N

Fe

II
V

III
N

M
GLOBIN

O2
N

Ket hp vi O2

Lien ket phoi tr gia His E7 va Fe2+ b t, mot phan

t oxy se the cho His E7 e gan vi Fe2+.

Ket hp vi O2
- 1 nguyen t Fe cua Hem gan vi mot phan t O2,
- 1 phan t Hb gan c bon phan t O2.
- 1g Hb gan c 1,34 ml oxygen.

Cau hnh khong gan oxy (Deoxyhemoglobin):

- dang cang hay trang thai T (Tense)

- Co ai lc yeu oi vi oxy.
- Dimer tng tac vi nhau qua he thong lien ket hydro va ion.
- Ben vng nh s hnh thanh cac cau muoi gia cac chuoi

Cau hnh gan oxy (Oxyhemoglobin):

- Dang dan hay trang thai R (Relax)
- Co ai lc manh oi vi oxy
- Lien ket hydro va ion gia cac dimer b cat t, cac cau muoi b
pha v, cac chuoi polypeptid di chuyen t do hn

Cac yeu to anh hng s ket hp gia Hb vi O2

Tng tac Hem - Hem
Cac tieu n v co tac ong cong lc: s ket hp cua 1
phan t oxy vi Hem au tien se lam tang ai lc cua oxy
vi cac Hem con lai
Phan ap cua oxy (pO2)
phoi: pO2 cao , phan ng xay ra theo chieu thuan tao
HbO2 theo mau en mo. (khoang 97% -98% Hb c
bao hoa O2 ).
mo: pO2 thap, phan ng xay ra theo chieu nghch,
HbO2 b phan ly nha O2 e cung cap cho cac mo.
Vai tro quan trong: van chuyen oxy t phoi en cac to chc

Cac yeu to anh hng s ket hp gia Hb vi O2

S thay oi cua pH (Hieu ng Bohr)
Khi pH cua mau giam hay khi phan ap CO2 (pCO2) tang,
kha nang ket hp vi oxy cua Hb giam,
Chat ieu hoa 2,3-diphosphoglycerat (2,3 DPG)
- San pham trung gian cua qua trnh thoai hoa glucid.
- Co kha nang ket hp va lam ben vng cau hnh T cua
phan t DeoxyHemoglobin, giam kha nang ket hp vi
oxy, kch thch giai phong oxy cac to chc.
-V tr ket hp: khe h gia 2 chuoi , trung tam phan t
deoxyhemoglobin

Cac yeu to anh hng s ket hp gia Hb vi O2

Chat ieu hoa 2,3-diphosphoglycerat (2,3 DPG)

S ket hp cua 2,3 - diphosphoglycerat (2,3-DPG) vi hemoglobin

Ket hp vi carbon dioxid (CO2)

Ket hp trc tiep
Qua nhom amin (-NH2) t do cua 4 chuoi polypeptid trong
globin tao thanh dan xuat carbaminoyl.(Carbohemoglobin):

R - NH2
Globin

CO2

R - NH - COOH
Carbohemoglobin

mo: pCO2 cao (46mmHg) phan ng xay ra theo chieu

thuan, carbohemoglobin c tao thanh theo mau en phoi.
phoi: pCO2 thap (36mmHg), phan ng xay ra theo chieu
nghch , phan ly giai phong CO2 va ao thai ra ngoai theo
ng ho hap.

Ket hp vi carbon dioxid (CO2)

Ket hp gian tiep
mo: H+ c tao thanh t CO2 :
Carbonic anhydrase

CO2 +

H2O

H2CO3

2H+ +

HCO3

2H+ ket hp vi Hb va phong thch 4 phan t oxy e tao thanh

2H+Hb, theo mau van chuyen ve phoi.
S tao H+, giam pH mau, nong o cao cua CO2 thuc ay s phong
thch oxy va ket hp vi CO2 tai mo
phoi: oxy gan vao deoxy Hb se ay H+ ra khoi Hb.
H+ ket hp vi bicarbonat giai phong CO2 ao thai ra ngoai theo
ng ho hap

Vai tro: Van chuyen CO2 t to chc en phoi e ao thai

ra ngoai bang ng ho hap

Ket hp vi carbon monoxid (CO)

- tao thanh carboxyhemoglobin (HbCO) rat ben vng,
khong con kha nang van chuyen oxygen.
Hb

CO

HbCO
Carboxyhemoglobin

- CO gan vao Hb tai v tr giong oxy, nhng co ai lc vi Hb

manh hn O2 gap 210 lan, nen co the ay O2 ra khoi HbO2
de dang:

HbO2

CO

HbCO

- HbCO gay ngo oc nang.

ieu tr: hon hp kh carbogen (95% O2 + 5% CO2)

O2

S oxy hoa Hemoglobin

Chat oxy hoa (nitrit, nitrat, clorat, ferricianur, nitrobenzen,
polyphenol, ..) oxy hoa Hb tao methemoglobin (M-Hb)
Hb

M - Hb

e-

Methemoglobin

M-Hb khong co kha nang gan O2 nen khong con chc nang ho hap.
M-Hb cao (> 1,5%) gay ngo oc, ngat th, da tm tai v thieu oxy mo
(hoi chng cyanose)
enzym diaphorase/c the kh M-Hb thanh Hb.
ieu tr: tiem cac chat kh manh (xanh metylen, vitamin C....)

Bnh thng Met Hb < 2% . Met Hb tang trong:

- Ngo oc bi cac chat oxy hoa
- Thieu men kh Met Hb do di truyen
- Cac benh Met Hb mau do cac dang Hb bat thng (HbM)

Tnh chat enzym cua hemoglobin

Tnh chat cua peroxidase
Xuc tac phan ng phan huy H202 :
Hb hay Peroxidase

AH2

H202

2H2O

ng dung: tm mau trong nc tieu va phan.

Tnh chat cua catalase

Hb hay catalase

2H2O2

2H2O

O2