CHlJdNG
4
CHUYEN
HOA
HEMOGLOBIN
MUC
TIEU
1.
Trinh
bay
va
giai
thich
dtfdc
tien
trinh
va
cd
chd
cua
qua
trinh
sinh
tdng
hdp
hemoglobin.
2.
Trinh
bay
va
giai
thich
dtfdc
tien
trinh
va
cd
che
ciia
qua
trinh
thoai
hda
hemoglobin.
3.
Neu
va
giai
thich
dtfdc
nhtfng
benh
ly
gay
ra
do
rd'i
loan
chuyen
hda
hemoglobin.
1.
SINH
TONG
H0P
HEMOGLOBIN
1.1.
Sinh tdng
hcfp
hem
Hem
cd
cau
triic
gdm
nhan
protoporphyrin
III
ket
hdp
vdi
Fe"+.
Stf
tdng
hdp
hem
xay
ra
trong
hau
het
te
bao
ngoai
trtf
hong
cau
trtfdng
thanh
vi
khong
cd
ty
the.
Khoang
85%
stf
tdng
hdp hemxay ra d te bao tien
hong
cau
trong
tuy
xtfdng.
1.1.1.
Tong
hcfp
nhan
protoporphyrin
III
Hai
nguyen
lieu
khdi
dau
cho
qua
trinh
tdng
hdp
nhan
porphyrin
ttf
do
tao
hem
la
succinyl
CoA
va
glycin.
Succinyl
CoA
la
mot
cha't
trung
gian
ciia
chu
trinh
acid
citric,
con
glycin
la mot acid amin . Qua
trinh
tdng hdp nhan protoporphyrin qua cac giai doan sau:
1.1.1.1.
Tao
acid
5 -
amino
levulinic
(ALA)
Stf
tdng
hdp
ALA
xay
ra d
ty
the,
ndi
ma
succinyl
CoA
dtfdc
tao
thanh
trong
cac
phan
tfng
ciia
chu
trinh
acid
citric.
Glycin
dtfdc
hoat
hda
bdi
pyridoxal
phosphat
(vitamin
B6)
Succinyl
CoA
ket
hdp
vdi
glycin,
loai
CoA
tao
thanh
acid
a-
amino
-P
-
ceto
adipic.
Chat
nay
nhanh
chdng
bi
khtf
carboxyl
de
tao
thanh
acid
5
-amino
levulinic
(ALA)
vdi
stf
xiic
tac
ciia
enzym
ALA
synthetase vdi
coenzym
la
pyridoxal
phosphat:
COOH COOH
COOH
I I I
CH9 CH9 CHo
I I I
CH
2
CH2
CH2
I _ . I
ALA
synthetase
I
CO-SCoA
HSCoA
CO
pyridoxal
phosphat
fO
+
*"
CH-NH2
T^n*"
CH2-NH2
CH2-NH2
J^n
";
UU2
i00u
(COOjH
Ac[d
a.amlno
levulinic
(ALA)
Acid
a-amino
p-cetoadipic
Succinyl
CoA
Glycin
1.1.1.2.
Tao
porphobilinogen
ALA
dtfdc
tao thanh se di
chuyen
den bao
ttfdng.
Tai day, hai phan ttf
ALA
ngtfng
tu
vdi
nhau
(loai
2
phan
ttf
H20)
va
dong
vdng
pyrol
tao
thanh
porphobilinogen
vdi
stf
xiic
tac
ciia
enzym
ALA
dehydratase
(porphobilinogen
synthase),
enzym
nay
bi
tfc
che
bdi
chi
kim
loai
(Pb).
102
COOH
I
CH2
C
H2
O
A
COOH
I
CH2
CHP
I
C
^2Ha°
Ql_j
/\LA
dehydratase
COOH
CH
COOH
COOH
CK
NH2
-
CH2
OH.
/
N
NH^CH^
^N/VH NH2-CH2 N
2 H
Porphobilinogen
1.1.1.3. Tao uroporphyrinogen
Bon
phan
ttf
porphobilinogen
ket
hdp
vdi
nhau,
loai
3
NH3
tao
thanh
mot
tetrapyrol
mach
thing
va
chat
nay
lai
tidp
tuc
loai
NH3
va
dong
vong,
cac
nhan
pyrol
ndi
vdi
nhau
blng
ciu
ndi
-
CH2
cd
the
tao
thanh
uroporphyrinogen
I
(enzym
xiic
tac
ia
uroporphyrinogen
synthetase)
va
uroporphyrinogen
HI
(enzym
xuc
tac
la
uroporphyrinogen
cosynthetase).
Hai
chat
nay
chi
khac
nhau
ve
vi
tri
ciia
2
nhdm
the
d
nhan
pyrol
TV.
Binh
thtfdng,
dong
phan
dtfdc
tao
thanh
hau
nhtf
deu
la
uroporphyrinogen
III.
Khi
cd
rdi
loan
chuyen
hda
porphyrin
mdi
tao
thanh
uroporphyrinogen
I
H,N-CH
3NH3
uroporphyrinogenase
A
H.N-CH,
\ ,p
N_
IV
^NH
hn(
II
N
p/
\
Uroporphyrinogen
•PA, -P A.
CH2/Vs^AcH2Ax^\cH2
N N
H H
A
A\
/"
N
IV
)nh
hn(
II
N
p'\
Uroporphyrinogen
A
103
1.1.1.4.
Tao coproporphyrinogen III , ,
~-
Uroporphyrinogen
III
chuvdn
thanh
coproporphyrinogen
III
nhd
stf
khtf
carboxyl
cua
tot
ca
cac
gdc
acetat
(A)
d
mach
nhanh
dd
chuydn
thanh
cac
gdc
metyl
(M)
vdi
stf
xiic
tac
cua
enzym
uroporphyrinogen
decarboxylase.
IV
>NH
HN<^
II
N
III
,M
p/
M
Coproporphyrinogen
III
1.1.1.5.
Tao protoporphyrin III 7 x
Coproporphyrinogen
III
rdi
bao
ttfdng
vao
ty
thd.
d
day,
nd
bi
khtf
carboxyl
va
oxy
hoa
di
chuydn
hai
nhdm
thd
propionat
(-
CH2
-
CH2
-
COOH)
d2
nhan
pyrol
I
va
II
thanh
2
nhdm
vinyl
(-
CH
=
CH2)
tao
thanh
protoporphyrinogen
III
vdi
stf
xiic
tac
cua
enzym
coproporphyrinogen
oxydase
(chi
tac
dong
tren
cd
cha't
la
coproporphyrinogen
III).
Protoporphyrinogen
III
tidp
tuc
bi
oxy
hda
dd
chuydn
cau
noi
-
CH2
-
gitfa
cac
nhan
pyrol
thanh
clu
ndi
methenyl
(-CH=),
tao
protoporphyrin
HI.
Enzym
xiic
tac
la
protoporphyrinogen
oxydase.
,M
V
Protoporphyrin
111
(IX)
1.1.1.6.
Tao
hem
. . , u
5
ty
thd,
protoporphyrin
III
kdt
hdp
vdi
Fe2+
tao
hem,
nhd
stf
xuc
tac
cua
enzym
hem
synthase
(ferrochelatase).
Transferin
cua
huydt
ttfdng
(f3
globulin
chtfa
Fe
+)
lam
nhiem
vu
van
chuyen
sat
den
cac
cd quan tao mau.
1.2.
Tong
ho*p
Globin s
Qua
trinh
tdng
hdp
globin
cung
theo
cd
chd
chung
cua
qua
trinh
sinh
tong
hdp
protein
Nguyen
lieu
la
cac
acid
amin
cung
stf
tham
gia
cua
nhidu
ydu
to
khac
nhtf
acid
nucleic
(ADN
va
ARN),
vitamin
(acid
folic,
B12),
cac
cha't
cung
cap
nang
ltfdng
(ATP,
GTP).
1.3.
Stf
ke't
hdp
gitfa
hem
va
globin
dd
tao
thanh
hemoglobin
104
"
Sau
khi
dtfdc
tong
hdp
xong,
hem
rdi
ty
thd
ra
bao
ttfdng
de
kdt
hdp
vdi
globin.
Stf
kdt
hdp
gitfa
hem
va
globin
dtfdc
thtfc
hien
qua
lien
kdt
pho'i
tri
gitfa
Fe
cua
hem
vdi
nitd
imidazol
(histidin)
ciia
globin.
Qua
trinh
tdng
hdp
hemoglobin
xay
ra
chii
ydu
d
cd
quan
tao
mau
nhtf
tuy
xtfdng
va
cac
hong
cau
non.
2.
THOAI
HOA
HEMOGLOBIN
H6ng
clu
ngtfdi
cd
ddi
song
trung
binh
khodng
120
ngay,
trong
thdi
gian
nay
Hb
khong
bi
bien
doi.
Khi
hong
du
chet,
Hb
se
dtfdc
giai
phdng
va
bi
thoai
hda.
Trong
didu
kien
sinh
If
d
ngtfdi
trtfdng
thanh
binh
thtfdng,
cd
ttf
1
-2
x
108
hdng
clu
bi
thoai
hda
trong
1
gid.Trtf
Fe
va
globin,
nhffng
san
pham
thoai
hda
ciia
porphyrin
khong
dtfdc
cd
the
stf
dung
trd
lai.
Stf
thoai
hda
Hb
xay
ra
chii
yeu
d
nhffng
te
bao
thuoc
he
tho'ng
vdng
noi
mo
nhtf
gan,
lach, tuy xtfdng....
Khi
hemoglobin
bi
phan
huy
se
giai
phdng
globin
va
hem:
-
Globin
chuyen
hda
theo
con
dtfdng
thoai
hda
ciia
protein
noi
bao
de
tao
acid
amin,
- Hem se thoai hda Ian ltfdt tao thanh sac td mat:
2.1.
Tao
biliverdin
Dtfdi
tac
dong
ciia
enzym
hem
oxygenase,
vdng
porphyrin
cua
hem
bi
md
gitfa
nhan
pyrol
I
va
II
bang
each
oxy
hda
va
loai
Cd
cau
ndi
methenyl
a
dtfdi
dang
carbon
monoxid
(CO),
giai
phdng
sat
dtfdi
dang
Fe3+
tao
thanh
biliverdin
(sac
td
mat
mau
xanh).
Fe
tach
ra
ket
hdp
vdi
mot
protid
van
chuyen
la
transferin,
dtfdc
mau
dtfa
den
tuy
xtfdng
de dung lai.
M,
V
l%^{
Biliverdin
Hinh 4.1. Sd do phan tfng tao sac to'mat biliverdin.
2.2.
Tao
bilirubin
Biliverdin
nhanh
chdng
bi
khtf
d
cau
no'i
-
CH=
tai
vi
tri
y(
cong
Hd
Cy,
N
kdt
hdp
vdi
H
va
cac
no'i
doi
se
di
chuyen)
tao
thanh
bilirubin
(sac
td
mat
cd
mau
vang
xanh)
vdi
stf
xiic
tac
105
ciia
enzym
biliverdin
reductase,
co
coenzym
la
NADPH
cung
cap
hydro.
Bilirubin
nay
khd
tan
trong^ntfdc,
cho
phan
tfng
mau
diazo
cham
va
gian
tidp,
goi
la
bilirubin
ttf
do
hay
gian
tiep.
Sau
khi
tao
thanh
d
mo
ngoai
vi,
nd
dtfdc
chuyen
vao
mau
ket
hdp
vdi
albumin,
globulin
ciia
huyet
thanh
va
theo
mau
den
gan.Vi
no
la chat
tan
trong
lipid
nen co the
tham
qua
mang
te
bao
gan
dd dang va tach khoi albumin, globulin.
Bilirubin
Hinh
4.2.
Cau
triic ciia
sac
td
mat
bilirubin.
2.2.
Su*
lien hr/p bilirubin d gan
Tai
gan,
bilirubin
ttf
do
lien
hdp
vdi
1
hay
2
phan
ttf
acid
glucuronic
tao
thanh
dang
lien
hdp
bilirubinmonoglucuronat
(20%)
va
bilirubindiglucuronat
(80%).
Phan
tfng
xay
ra
gitfa
2
nhdm
carboxyl
(-COOH)
ciia
gd'c
propionat
(P)
d
mach
nhanh
ciia
bilirubin
vdi
nhdm
OH ban acetal
ciia
acid
glucuronic.
Acid
glucuronic
d
dtfdi
dang
hoat hda
uridin
diphosphat
glucuronat
va
phan
tfng
lien
hdp
dtfdc
xiic
tac
bdi
enzym
glucuronyl
transferase.
Bilirubin
lien
hdp
tan
dtfdc
trong
ntfdc,
cho
phan
tfng
mau
diazo
nhanh
va
trtfc
tiep,
goi
la
bilirubin
trtfc
tiep.
Bilirubin
lien
hdp
dtfdc
bai
tie't
vao
mat
theo
mot
cd
che
van
chuyen
chu
dong
rdi
theo
6'ng
dan mat dd vao
ruot.
Binh
thtfdng,
trong
mat
ngtfdi
biliverdin
cd
mot
ltfdng
rat
nho
con
bilirubin
chiem
khoang
15-20% trong ltfdng kho.
OOC
coo-
Bilirubin
diglucoronat
Hinh
4.3.
Cau
triic ciia bilirubin
lien
hdp.
106