I HC QUC GIA TP.

H CH MINH
TRNG I HC BCH KHOA
KHOA K THUT HA HC
...............0 CO 03..............................

TIU LUN HA SINH THC PHM

ti:

HEMOGLOBIN V MYOGLOBIN

GVHD : TS. TRN BCH LAM

NHM THC HIN:
HUNH HONG DUY
L TRN TRUNG
PHAN BO DUNG
TRN CAO DN
INH TH T UYN

60800300
60802379
60800288
60800272
60802571

T THANH LOAN

Mc Lc

60801123

CHNG I. Hemoglobin.................................................Error! Bookmark not defined.

1.1 .cu to hemoglobin....................................................Error! Bookmark not defined.

HEMOGLOBIN V MYOGLOBIN......................................1
Chng I: Hemoglobin...........................................................................................................................................3

HS-40 5' m........................................9

Embryo...................................................9
Porphyrin I.............................................14
Chng II: MYOGLOBIN...................................................................................................................................18

Oxy ho............................................23
Metmyoglobin Fe3+(mu nu)............................23
CC BIN I CHNH CA MYOGLOBIN TRONG THT (GD - globn
b bii tnh)........................................25

Ti liu tham kho

Chng I: Hemoglobin
1.1 Cu to :
Hemoglobin l huyt cu t ( Hb) mt cromoprotein c mu trong hng cu ng vt bc
cao.
Hemoglobin cu to gm hai phn :
phn protein thun : globin phn
nhm ngoi hem

Heme
<xchan
2

Heme

1.1.1 Hem :

Hemoglobin molecule

Hnh 1.1 cu trc bc bn ca hemoglobin

heme
protoporphyrin IX

Hs

c to thnh t protoporphyrin IX gn vi mt nguyn t Fe ha tr hai ( Fe2+ ) bi bn

lin kt vi 4 nito ca bn vng piron. Nhm hem b oxy ha thnh
hemantin
Hnh 1.2
Protopocp
h irin IX
(1,3,5,8tetrametyl
- 2,4divinyl6,7dipropionic
pocphirin)

CH =CHj

Ferrochel atase
CH22
CH

I.

COO
COO
'CO
'
O'

Fe2+ thnh Fe3+

vng protopocphirin : c cu to t bn vng piron ni vi nhau qua cu meten to thnh
vng tetrapiron. 4 nhm metyl, 2 nhm vinyl v 2 nhm propionat c the gn vo 15 v tr
khc nhau ca vng protopocphirin

1.1.2 Globin :
CH

H3C

CH = CH 2

H3C

CH3

COOH

COOH

ngi trng thnh gm 4 chui polypeptide trong c

hai chui a mi chui gm 141 acid amin

 hai chui [3 mi chui gm 146 acid amin

Ton b phn t Hb cha 574 acid amin. cu trc bc 2 ca hemoglobin cc chui a v p c

hn 70% acid amin to nn to nn 7 chui xon a v 8 chui xon |3 c chiu di t 7 n
20 acid amin .Trong cu trc bc 3 Hb cc chui a v p cun khc ti nhng im acid amin
khng xon ging cu trc bc 3 ca myoglobin .Mi mt chui polypeptide xon kt hp
vi mt Hem to thnh phn t Hemoglobin c cu trc bc bn

"Shortiand" cx-helix

cu trc bc 2 v bc 3 ca hemoglobin

cu trc bc 2 v bc 3 ca hemoglobin

Garrett &
Grisham:
Biochemistry,
Figure 15.24

2/e

* S tng

hp globin

Transferrin

Saunders College
Publishing

Hnh I . M hnh 1 chui ca Hb

Hnh 7:

Tng hp Hemoglobin

Nhng loi globin khc nhau kt hp vi hem to thnh cc Hb khc nhau

Nhng gen m ha cc chui globin:
b, g, d v e nm trn nhnh ngn nhim sc th 11
a v z nm trn nhnh ngn nhim sc th 16

-2

(*1

5'

Chromosome 11 Chromosome 16
LCR I HS-40 5' m

HEMOGLOBIN V MYOGLOBIN........................1
Chng I: Hemoglobin...................................................................................................3

HS-40 5' m...........................9

Embryo.....................................9
Porphyrin I...............................14
Chng II: MYOGLOBIN...........................................................................................18

Oxy ho...............................23
Metmyoglobin Fe3+(mu nu)..............23
CC BIN I CHNH CA MYOGLOBIN TRONG
THT (GD - globn b bii tnh)........25
Embryo

n u n u nU^.
& Ok L
h
"p
22
F

p
"
a2 F
A2

1
2

.A

Fetus

Adult

Globin bt u c tng hp t tun th 3 ca thai k

Phi
Hemoglobin Gower I ( z2e2)
Hemoglobin Portland ( z2g2)
Hemoglobin Gower II (a2e2)
Thai: HbF (a2g2), HbA (a2b2)
Ngi ln : HbA, HbA2 ( a2d2), HbF.

tu xng

Tiii non

Prenatal age (weeks)

Cu trc
%

Hb A
A2b2
95-97%

Bng thnh phn hemoglobin ca ngi ln

Hb A2
A2d2
2-3.5%

Hb F
A2g2
1-2%

1.1.3. S kt hp ca Hem v Globin

mi chui J30lypeptide ca Globin kt hp vi mt Hem qua hai lin kt phi tr
gia Fe ca hem vi N ca nhn Imidazol thuc acid amin histidin E7 vi N ca
nhn Imidazol thuc acid amin F8 trong chui polypeptide
biu din Hem trn mt mt phng th hai liu kt phi tr gia Fe 2+ vi globin nm
v hai pha mt phng
HIS (E 7 )

0=0

H IS (F8)

HIS

(F 8 )

Phn t Hb hon chnh l mt protein hnh cu c ng knh khong 55A phn t lng
64454.Hb gm 4 n v ging nhau tng i mt lin kt vi nhau bng lin kt phi ng
ha tr, mi bn n v gm mt chui polypeptide ca globin lin kt vi mt hcm l v tr
nh v gn oxy.T l st trong hemoglobin l 0,34%
M

1.2

Tnh
cht ca

hemoglobin :
1.2.1 Kt hp thun nghch vi oxy to oxyhemoglobin
Hb 1+
* 2 = Hb02
thm
ti
S kt hp v phn ly gia 02 v Hb c xc nh bi phn p oxygen mi trng
chung quanh Hb.
phi: phn p 02 cao 95-98% Hb kt hp oxy theo mu n m.
m: phn p 02 thp (40mmHg) phn ng xy ra theo chiu nghch, Hb02 phn
ly, nh 02 cho m
chc nng ca Hb trong h hp.
ng cong phn ly oxy -hemoglobin:
S kt hp v phn ly gia 02 v Hb c xc nh bi phn p oxy (p02)
C dng Sigma
Vic gn oxy vo hem th nht lm d dng gan oxy vo hem th 2

1Lch tri (d gn oxy)

p 50 (phn p 02 cn thit 50% Hb bo ha vi 02) 26.8mmHg

ng cong phn ly
oxy hemoglobin

partial pressure of oxygen

* phn P02 thp (ni Hb02 nh 02 cho m): ng cong rt dc 1 s thay i nh ca P02
s lm thay i s giao 02 cho m mt cch ng k => gip hng nh P02/m.
* phn P02 cao (ni Hb ly 02 t phi) ng cong t:
P02: 60mmHg bo ha Hb vi 02: 89%.
P02 t 500 th bo ha Hb02 cng ch 100%
> P02 mi trng, ph nang c th thay i nhiu nhng bo ha Hb02 & lng oxy giao
m khng b giao ng lm.
=> P02 m on nh.
=> Hb c tnh m gip P02/ m n nh, m bo s hng nh ni mi.
V tr bnh thn ca ng cong ty thuc vo:
S Nng 2,3-DPG s Nng ion H+ (pH)
S C02 trong hng cu s Cu trc ca Hb...

Lch phi (dc nh oxy)

2,3-DPG cao
H+ cao
C02 cao
Hb

Oxyhaemoqlobin____________Deoxhaemoglobin

Hnh 1.3 oxy-deoxy hemoglobin

2,3-DPG thp

Val FG5
Leu FG3

Leu F4

0.6 A

Heme
-s

_ i _ _ His F8

Porphyri
n

Porphyrin I

Helix F

Leu F7

Hnh 1.4 Lin kt ca oxy trong hemoglobin

(b)
(a)

Hnh 1.5 Oxy v deoxy hemoglobin trong khng gian

1.2.2 Ket hp vi cacbodioxyll to thnh cacbonyl hemoglobin
CO2: Sn phm chuyn ha cc mthi ra ngoi Mu
TM: 50-60ml CCVlOOml mu Mu M: 50-53ml
CCVlOOml mu.
P02 = 40mmHg, 37 o c, ch 2,9ml CO2 ha tan phi vn chuyn bng nhiu cch.
a) Hb kt hp trc tip vi CO2: qua nhm NH2 t do ca Globin to thnh
carbonyl Hb(HbC02)
R-NH2 +
CO2 <-> R-NH-COOH
(dn xut carbamyl) p/
xy ra hoc < ty thuc Pc:o2
* m : pC02 = 46mmHg : phn ng theo chiu thun *
phi: pC02 = 36mmHg : phn ng theo chiu nghch b Hb
vn chuyn gin tip COo CO2 thm thu t cc m vo
mu:
CO2 + H2O
H2CO3 ^ H+ + HCO'3
CA ( carbonic anhydrase)

15

H+ gn vo His (146) tn cng chui p ca Hb t do (va gii phng O) to Hb2H+

n phi: H+ c gii
phng
+
HCO3' => H2CO3
H2CO3

H2O

CA

+ CO2T

1.2.3 Ket hp vi cacbonmonoxyl to cacbonmonoxyl hemoglobin ( COHb)

to carbon monoxyd Hb (HbCO) rt bn vng.
> CO c i lc vi Hb gp 210 ln so vi oxy
> CO c th y O2 ra khi HbOo
Hb + CO
HbCO
Hb2 + CO
HbCO +
O2
> Trong trng hp ng c co, ngi ta phi gi tt kh cho bnh nhn
Ni tm li: Hemoglobin c kh nng kt hp vi CO, CO2 lrt ba trung tm khc nhau tng
tc ca cc trung tm ny c truyn bng nhng thay i dng khng gian ca phn t
protein gi l tng tc aosteht
1.2.4.Oxy ha Hb to Methemoglobin (MetHb):
cht oxy ha Hb
(Fe )

MetHb + e'
(Fe )

nitrit, clorat,
ferricyanua...

I.2.5.
Tnh cht enzym:
Hb c tnh cht ca mt oxydoreductase xc tc phn ng oxi ha kh s
Tnh cht ca mt peroxydase:
H2O2 + AH2
2H2O +
A
Hb
s Tnh cht ca mt catalase:
H2O2

2H2O + O2

16

Garrett & Grisham: Biochemistry,

2/e Figure 15.26

HLs E7

His E7

N'

HC-.

CH

CH

-N

HC.

N'
/

TV

His F8

HLs F8

N
(a) Free heme
with imidazole

N
(b) Mb:CO complex

(c)

Oxymyoglobin

Saunders College

1.3 Chc nng sinh hc ca hemoglobin

Vn chuyn oxy n m
Phn ng gia Hb & oxygen:
S gn oxy - khng phi phn ng oxy ha.

Mt Hb c th gn 4 phn t 02.

S gn oxy i hi t hn 0.01 giy.

Chu nh hng ca mt s cht: 2,3-DPG (2,3Diphosphoglycerate)...

Publishing

Chng II: MYOGLOBIN

II.l Cu to :

Hnh 2.1 cu trc khng gian ca Myoglobin

Myoglobin l protein c cu trc bc 3 in hnh, sc t ch yu ca c tht ng vt

Khi lng phn t trung bnh 16,700 daltons

18

Mt phn t Myoglobin ch gm mt n v, khng phi l bn n v nh Hemoglobin.

Phn t Globin ca Myoglobin do 153 gc acid amin to nn, trong 121 gc tham gia
vo cu trc xon a, gm 8 phn, mi phn cha t 7-26 gc.
- Nhm heme (st cha porphyrin) nhm phn gi trung tm quanh gp apoprotein cn
li. N c tm helices alpha v li mt hydrophobic.
TABLE 9-1. T HE

A MINO A CID S EQUENCES

Helix Boundaries A1

of THE a AND
A16B1

C HAINS

of H UMAN
B16
Cl

H EMOGLOBIN

C7

AND OF

D1

H UMAN M YOGLOBIN 4 -*

D7
El

HEMOGLOBIN V MYOGLOBIN.......................................1
Chng I: Hemoglobin................................................................................................................................................3

HS-40 5' m........................................9

Embryo....................................................9
Porphyrin I..............................................14
Chng II: MYOGLOBIN........................................................................................................................................18

Oxy ho............................................23
Metmyoglobin Fe3+(mu nu).............................23
CC BIN I CHNH CA MYOGLOBIN TRONG THT (GD - globn
b bii tnh).........................................25
Mb...............................G - L S D G E W Q L V L N V W G K V E A D I P G H G Q E V L I R L F K ^ H P E T L E K F D K F K H L K S E D E M K A S E D L K K H G A T V L T A L G

The residues have been aligned in structurally analogous positions. The

blue boxes shade the residues that are identical in both Hb chains, the
purple boxes shade the residues that are identical in both Hb chains and in
Mb, and the dark purple boxes shade residues that are invariant in all
vertebrate Hb and Mb chains (Thr C4, Phe CD1, Leu F4, His F8, and Tyr
HC2). The one-letter amino acid symbols are defined in Table 4-1.
E19

FI

F9

G1

'The first and last residues in helices A-H are indicated, whereas the
residues between helices constitute the intervening segments. The refined
Hb structure reveals that much of what is designated the EF segment is
really helical in both chains: It encompasses residues EF4-F2 and is designated the F' helix.
G19 HI

H19
H21

H26

HEMOGLOBIN V MYOGLOBIN....................................1
Chng I: Hemoglobin.......................................................................................................................................3

HS-40 5' m.......................................9

Embryo.................................................9
Porphyrin I...........................................14
Chng II: MYOGLOBIN...............................................................................................................................18

Oxy ho...........................................23
Metmyoglobin Fe3+(mu nu)..........................23
CC BIN I CHNH CA MYOGLOBIN TRONG THT (GD globn b bii tnh)...............................25

19

Mb........G I L K K K G H H E A E i K P | a Q S | T K H K I P V K Y L E F I S E C I I Q V L Q S K H P G D F G A D A Q G A M N K A L E L F R K D M A S N

Myoglobin cha mt vng porphyrin vi mt trung tm st. C mt nhm histidine proximal

gn trc tip n tning tm st, v mt nhm histidine ngoi bin trn mt i din, khng phi
ngoi quan n st. N phc v ba chc nng:

20

1. hnh thnh lin kt hydro vi cc phn na dioxygen, tng o 2 rng buc khng i
2. ngn chn s rng buc ca kh carbon monoxide, cho d c hoc khng c t bn trong c th.
Carbon monoxide lin kt vi st trong mt ngy cui thi trang, v l cn tr bi s hin din ca
cc histidine ngoi bin, m lc lng n thnh mt conformation cong, co lin kt vi heme 23.000
ln tt hn so vi
o 2 nhng ch c 200 ln tt hn trong hemoglobin v myoglobin. Oxy gn trong mt thi trang b
cong, m c th ph hp vi histidine ngoi bin. [l2]
3. e ngn chn dimerization khng th o ngc ca oxymyoglobin vi mt loi
deoxymyoglobin

Hnh 2.2 Lin kt ca nhm hem trung myoglobin

21

Mt trong 2 phi tr t do ca Fe c lin kt vi mt trong cc histidine ny, v cn li mt phi tr

t do trn Fe nm pha kia ca vng s lin kt vi oxygen

heme plane
11.2 Chc
nng
ca
chnh

chuyn
ch
mitochondria)

Xc tc vt vc NO

(p rotein chain)^/^!

Myoglobin cng c mt chc nng

Myoglobin thot ra khi m
tiu c mu hng
C tc dng l mt kho d tr kh
phng thch oxy khi nng xung
d tr kh cho c th
11.3 Tnh cht ca myoglobin

myoglobin : c hai chc nng

kh (t hng huyt cu vo ni bo

dng
H

d tr dng kh cho m tht

gin tip trong trng hp thng tn bp tht.
tht b thng tn v lc vo trong nc tiu lm nc
myoglobin gn cht vi oxy hn hemoglobin n ch
thp nn thch hp hn hemoglobin trong qu trnh

22

D esoxymyoglobin
Fe2+( ta)

Oxymyoglobin
phn ng cng oxy

Fe2+( ti)

Oxy ho

Oxy ho

Kh

Kh

Metmyoglobin
Fe3+(mu nu)
V
Desoxymioglobin l sc t bm sinh ca tht lm cho tht c mu ta, trong Fe c
ha tr II.
Myoglobin (Mb) khi mang oxy to thnh Oxymyoglobin (Mb02) c mu rc. Mb02
l cht d tr oxy cho c, trong Fe c ha tr II. Mu ca Mb02 c th nhn thy r
trn b mt tht ti.
Mb v Mb02 khi b oxy ha th Fe2+ chuyn thnh Fe3+ to nn Metmyoglobin (MMb)
c mu nu. Khi nguyn t Fe trng thi Fe3+ th phn t Mb khng c kh nng kt
hp vi oxy na.

23

Mb2+ hoc MbOo

ferrihemochrom

Nitrosomyoglobin
Nitrit

Nhit

Fe2-, Globin

hoc
nitrat

kh

iu kin

Fe3+, Globin
bin tnh,mu
nn

khng bin tnh,

+
nhit

Oxy

mn (n
Ferrohemochro

Nitrosoferrohemochrom

ha

Fe2+ , Globin bin

tnh, mu hng

2+

Fe , Globin bin tnh, mu hng

II.3 Bin tnh ca Myoglobin trong qu trnh ch bin v bo qun thc phm :
> Lng Mb thay i ty tng loi m, tng loi, tui, gii tnh dn n mu sc tht
cng thay i theo. tui cng cao th lng Mb cng nhiu nn tht ca con vt gi
c mu m hn ca con vt non. nhng c vn ng th nhiu Mb hn cc c khc.
S nh hng ca lng Mb n mu sc ca tht c th hin trong bng 1 (a,b,c).

CC BIN I CHNH CA MYOGLOBIN TRONG THT (GD - globn b bii

tnh)
nitrit

MbdCO (Fe2+,GD)

c a cb oxy fer ohemo crom

Phc khng mu

Quang

MbdNO(Fe^,GD)
N ltr oz ofer oh emo crom

Pocphirin r do, b
oxy ho

Cho lemy o g

(nu,vng, khng

lob in (xanh l
cy)

a.theo loi
Loi

Lng
Myoglobin(mg/g)

Mu

Tht heo

Hng

Tht cu

nht

Tht b

anh o

b.thco loi c
Loi CO'

Lng mvoglobin

C vn ng

12 mg/g

C tr

6mg/g

26

c.theo tui
Loi
(theo tui)

Lng
myoglobin(mg/g)

Tht b

Tht b (non)

Tht b (non)

Tht b (gi)

18

Ti liu tham kho : Ha sinh cng nghip . L Ngc T ( ch bin ) Nh xut bn khoa hc k
thut H Ni
Ha sinh y dc

27