1. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Ch 脱 奪 n g 7
ACID NUCLEIC
Mu短c ti達u:
1. Vi達炭t 但脱奪端c c辰ng th脱誰c tha狸nh ph叩旦n c叩炭u ta短o cu鱈a
acid desoxyribonucleic (ADN) va狸 cu鱈a acid ribonucleic (ARN).
2. M辰 ta鱈 但脱奪端c 但短c 但i達淡m c叩炭u tru誰c cu鱈a ADN va狸 ARN.
3. K達淡 但脱奪端c ca誰c sa鱈n ph叩淡m thoa誰i ho誰a trung gian va狸
ca誰c sa鱈n ph叩淡m thoa誰i ho誰a cu辰炭i cu狸ng cu鱈a acid nucleic.
4. M辰 ta鱈 但脱奪端c qua誰 tr巽nh t辰淡ng h奪端p ADN, ARN.
5. N達u ra 但脱奪端c y誰 ngh辿a l叩m sa狸ng cu鱈a s脱短 chuy達淡n
ho誰a acid nucleic.
Ph叩旦 n 1.
HOA HOC ACID NUCLEIC
I. AI CNG.
Acid nucleic (AN) la狸 h奪端p ch叩炭t quan tro端ng b叩短c nh叩炭t
trong s脱短 di truy達旦n va狸 t辰淡ng h奪端p protein. T叩炭t ca鱈 c奪 th達淡
s辰炭ng 但達旦u ch脱誰a AN d脱奪誰i da短ng t脱短 do ho短c d脱奪誰i da短ng
k達炭t h奪端p v奪誰i protein ta短o nucleoprotein
AN trong c奪 th達淡 d脱奪誰i 2 da短ng ch棚nh:
- Acid ribonucleic (ARN).
- Acid deoxyribonucleic (ADN).
II. THANH PH N CU TAO ACID NUCLEIC (AN):
Tha狸nh ph叩旦n c叩炭u ta短o AN g辰旦m: H 3 PO4 , pentose, base nit奪.
1. C叩炭u ta短o pent o s e
OH
CH2
O
OH
OH
OH
CH2
OH
OH
OH
O
H
硫- D ribose
硫-2 deoxy D ribose
H巽nh 7.1. Ribose va狸 Deoxyribose
2. C叩炭u ta短o cu鱈a bas e co誰 nit奪
Base co誰 nit奪 但脱奪端c d叩湛n xu叩炭t t脱狸 2 nh叩n d谷 vo狸ng la狸 purin
va狸 pyrimidin.
2.1. Bas e pyri m i d i n
Base co誰 nh叩n pyrimidin g辰旦m cytosin, uracil va狸 thymin (H巽nh
7.2)
134
2. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
1N
H
6C
HC
2
5
CH
CH
4
N
3
H
4C
3N
ho短
c
HC
2
5
CH
CH
6
N
1
Nh叩n pyrimidin
Cytosin (ky誰 hi達短u C): 2 hydroxy 6 amino pyrimidin:
NH 2
NH 2
N
HO
N
O
N
N
H
da短ng enol (lactim)
da短ng ceton (lactam)
Uracil (U): 2,6 dihydroxy pyrimidin:
OH
O
H
N
HO
N
O
N
N
H
da短ng enol
Thymin (T): 5 methyl uracil.
da短ng ceton
OH
N
HO
O
CH 3
H
O
N
CH 3
N
N
H
da短ng enol
da短ng ceton
H巽nh 7.2. Base pyrimidin: cytosin, uracil va狸 thymin
2.2. Bas e purin
Base co誰 nh叩n purin g辰旦m adenin va狸 guanin (H巽nh 7.3)
Ngoa狸i tha狸nh ph叩旦n tr達n, ARN, ADN co狸n ch脱誰a th達m
m辰端t s辰炭 base nit奪 kha誰c:
ADN vi khu叩淡n co誰 N.6 metyl adenin, 5 hydroxymetyl cytosin.
ADN th脱短c v叩短t (m叩旦m lu誰a), 但辰端ng v叩短t (tuy達炭n 脱誰c) co誰
5 metyl cytosin.
ARNr va狸 ARNt co狸n ch脱誰a base purin va狸 pyrimidin metyl
ho誰a. ARNt co狸n ch脱誰a pseudouridin; hypoxanthin; 1 metyl
hypoxanthin; 5,6 dihydrouracil.
135
3. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
6
1N
5
2
N
3
4
NH 2
N7
N
8
N
9
N
N
Nh叩n purin
N
Adenin (A): 06 amino
purin.
Guanin (G):
OH
N
H 2N
N
N
O
H
H
N
N
H 2N
N
N
H
N
H
Da短ng enol
Da短ng ceton
H巽nh 7.3. Base purin: adenin va狸 guanin
III. NUCLEOSID VA NUCLEOTID
1. Nucle o s i d
Nucleosid la狸 sa鱈n ph叩淡m thu鱈y ph叩n kh辰ng hoa狸n toa狸n
cu鱈a AN g辰旦m base nit奪 li達n k達炭t v奪誰i pentose b嘆ng li達n k達炭t
glucosid. Li達n k達炭t na狸y 但脱奪端c th脱短c hi達短n gi脱樽a C1 cu鱈a
pentose va狸 N3 cua鱈 base pyrimidin ho短c gi脱樽a C1 cu鱈a
pentose va狸 N9 cua鱈 base purin. (H巽nh 7.4)
Ca誰ch go 端i t達n:
Tu狸y theo tha狸nh ph叩旦n cu鱈a base nit奪 va狸 cu鱈a pentose ca誰ch
go端i t達n nh脱 sau:
T達n chung:
Ribonucleosid
Deoxyribosenucleosid
(Pentose la狸 Ribose)
(Deoxyribose)
T達n ri達ng cu鱈a ca誰c nucleosid theo base nit奪:
Adenin
Adenosin
Deoxyadenosin.
Guanin
Guanosin
Deoxyguanosin.
Uracil
Uridin
Deoxyuridin
(棚t)
Cytosin
Thymin
Cytidin
Ribothymidin
136
Deoxycytidin.
(棚t)
4. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Deoxythymidin.
NH2
N
N
N
N
O
Adenin
CH2OH
Ribose
OH OH
Adenosin
H巽nh 7.4. Nucleosid co誰 base adenin
2. Nucle oti d (nucl e o s i d pho s p h a t )
Ca誰c nucleosid th脱奪狸ng kh辰ng 奪鱈 tra短ng tha誰i t脱短 do ma狸
k達炭t h奪端p v奪誰i H 3 PO4 ta短o tha狸nh nucleotid, trong 但o誰 pentose
li達n k達炭t v奪誰i H 3 PO4 b奪鱈i li達n k達炭t este 奪鱈 ca誰c v谷 tr棚 2, 3, 5.
Nucleosid
monophosphat
co狸n
但脱奪端c
go端i
la狸
mononucleotid, 但奪n v谷 c叩炭u ta短o cu鱈a acid nucleic, g辰旦m co誰
base nit奪, pentose va狸 acid phosphoric (H巽nh 7.5.)
NH2
N
O
N
N
N
O
Adenin
CH2O
P
OH
OH
Ribose
OH OH
Adenosin-5'-monophosphat (AMP)
H巽nh 7.5. Nucleosid monophosphat co誰 base
adenin
Ca誰ch go端 i t達n:
Nucleotid co誰 tha狸nh ph叩旦n la狸 ribose, 但脱奪端c go端i la狸 ribonucleotid.
Nucleotid co誰 tha狸nh ph叩旦n la狸 deoxyribose, 但脱奪端c go端i la狸
deoxyribonucleotid.
Go端i theo base N: Ribosid 5 monophosphat
Deoxyribosid 5
monophosphat
Adenin:
Adenosin 5 monophosphat
137
5. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Deoxyadenosin5monophosphat (AMP) (dAMP)
Guanin: Guanosin 5 monophosphat Deoxyguanosin
5
monophosphat (GMP)
(dGMP)
Uracil: Uridin 5 monophosphat
Deoxyuridin5 monophosphat
(UMP)
(dUMP)
Cytosin: Cytidin 5 monophosphat
Deoxycytidin
5
monophosphat (CMP)
(dCMP)
Thymin: Thymin ribosid 5 monophosphat (棚t)
monophosphat
Deoxythymidin 5
(dTMP)
Ca誰c nucleotid co誰 th達淡 k達炭t h奪端p v奪誰i 2 ho短c 3 ph叩n t脱鱈 H 3 PO4
但達淡 ta短o tha狸nh nucleosid diphosphat va狸 nucleosid triphosphat gi脱樽
vai tro狸 quan tro端ng trong c奪 th達淡.
3. Ca誰c nucle o ti d t脱 短 do qua n tro端 n g
3.1. D叩湛 n xu叩炭 t ad e n i n
-Adenosin diphosphat va狸 triphosphat (ADP, ATP)
7.6)
(H巽nh
NH2
N
O
N
N
Adenin
N
O
CH2O
P
OH
O
O
O
P
OH
O
P
OH
OH
Ribose
OH OH
Adenosin-5'-monophosphat (AMP)
Adenosin-5'-diphosphat (ADP)
Adenosin-5'-triphosphat (ATP)
H巽nh 7.6. C叩炭u ta短o cu鱈a AMP, ADP va狸 ATP
- Vai tro狸 ADP va狸 ATP:
+ Tham gia pha鱈n 脱誰ng phosphoryl ho誰a.
+
ATP
la狸
ngu辰旦n
phosphat gia狸u nng l脱奪端ng, d脱短 tr脱樽 va狸 cung c叩炭p nng
l脱奪端ng cho ca誰c pha鱈n 脱誰ng.
+ Hoa短t ho誰a ca誰c ch叩炭t
+ Adenosin monophosphat vo狸ng (5, 3 adenosin
monophosphat = AMPv ).
138
6. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
AMP vo狸ng 但脱奪端c h巽nh tha狸nh t脱狸 ATP nh奪狸 enzym adenyl
cyclase xu誰c ta誰c, co誰 vai tro狸 nh脱 m辰端t ch叩炭t th辰ng tin th脱誰 hai
ma狸 hormon la狸 ch叩炭t th辰ng tin th脱誰 nh叩炭t, tham gia va狸o s脱短
hoa短t 但辰端ng 1 s辰炭 hormon, tham gia t辰淡ng h奪端p hormon (H巽nh
7.7).
- S-Adenosin methionin:
cung c叩炭p nho誰m metyl cho ca誰c qua誰 tr巽nh (H巽nh 7.8)
NH2
NH2
O
O
-
O
O
P
P
P
O
-
O
-
O
-
O CH2
O
N
ppi
N
N
N
N
N
N
O
Adenylat
cyclase
O
OH OH
P
5'
N
CH2
O
3'
O OH
n
Adenosin 3',5'-monophosphat vo狸 g
(AMPv)
ATP
H巽nh 7.7. Pha鱈n 脱誰ng ta短o tha狸nh AMPv
NH3
N
COOH
CH
CH2
CH2
NH2
N
N
CH2
CH2
S
O
N
+
OH OH
S_Ade ylmethion
nos
in
H巽nh 7.8. S-Adenosinmethionin
3.2. D叩湛n xu叩炭 t gua ni n : G uanosin di va狸 triphosphat
(GDP, GTP) co誰 vai tro狸 trong t辰淡ng h奪端p protein
3.3. D叩湛 n xu叩炭 t uracil: Uridin di va狸 triphosphat (UDP,
UTP) co誰 vai tro狸 trong chuy達淡n ho誰a glucid.
3.4. D叩湛 n xu叩炭 t cyt o s i n : Cytidin di va狸 triphosphat (CDP, CTP):
tham gia t辰淡ng h奪端p phospholipid.
IV. ACID NUCLEIC
1. C叩炭u tru誰c cu鱈a ADN
139
7. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
1.1. C叩炭u tru誰c b叩 短 c I
ADN la狸 polyme cu鱈a nhi達旦u deoxyribonucleotid co誰 ch脱誰a ca誰c
base nit奪 la狸 adenin, guanin, thymin, cytosin, nucleotid na狸y n辰炭i v奪誰i
nucleotid kia b奪鱈i li達n k達炭t 3, 5 phosphodieste ta短o tha狸nh chu辰湛i
polynucleotid. (H巽nh 7.9)
A
O
H2C
3'
O
HO
P
O
A
O
O
O
5' CH
2
O
T
O
G
3'
O
HO
P
O
H巽nh 7.9: C叩炭u tru誰c b叩短c 1 cu鱈a ADN
M辰端t 但oa短n polynucleotid cu鱈a ADN co誰 th達淡 bi達淡u th谷 ng探n
go端n nh脱 h巽nh d脱奪誰i 但叩y. Trong 但o誰 P bi達淡u th谷 li達n k達炭t
phosphodoieste, ca誰c ky誰 t脱短 b嘆ng base nit奪, 但oa短n th坦ng 但脱誰ng
b嘆ng 但脱奪狸ng pentose.
Ca誰ch vi達炭t: pA-C-G-T OH
hay pApCpGpT hay pACGT hay
ACGT v奪誰i 但叩旦u 5 phosphat v達旦 ph棚a tay tra誰i, 但叩旦u 3 OH v達旦 ph棚a
tay pha鱈i.
1.2. C叩炭u tru誰c b叩 短 c 2
- M辰湛i ph叩n t脱鱈 ADN g辰旦m 2 chu辰湛i polynucleotid xo探n theo
140
11. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Trong ca誰c sinh v叩短t 但奪n ba狸o va狸 但a ba狸o, co誰 3 loa短i ARN
ch棚nh: ARN th辰ng tin (ARNm), ARN v叩短n huy達淡n (ARNt) va狸 ARN
ribosom (ARNr).
- ARNm: mang th辰ng tin di truy達旦n ma狸 ADN 但a樽
phi達n ma樽 cho no誰 ra ribosom 但達淡 t辰淡ng h奪端p protein. Ph叩n t脱鱈鱈
ARNm la狸 m辰端t s奪端i polynucleotid da狸i, th坦ng ch脱誰a 900 12000 nucleotid, ph叩短n t脱鱈 l脱奪端ng khoa鱈ng 3x10 5 但達炭n 4x10 6 .
t達炭 ba狸o co誰 nh叩n 但叩旦u 5 co誰 mang m辰端t ph叩n t脱鱈 7methylguanosin triphosphat va狸 但脱奪端c go端i la狸 mu樽. 叩旦u 3
co誰 g探n nh脱樽ng nucleotid adenylat go端i la狸 但u辰i poly A co誰
t脱狸 20 - 250nucleotid (H巽nh 7.13).
OH OH
NH2
H2N
N
N
N O CH2
N
O
CH3
O
N
P
P
P
O
H2C
O
O
N
N
N
O CH3
H巽nh 7.13. Ph叩n t脱鱈 7-methylguanosin triphosphat
- ARN t: v叩短n chuy達淡n acid amin 但達炭n ribosom 但達淡 t辰淡ng
h奪端p protein. C叩炭u ta短o t脱狸 4 base ch棚nh: A, G, C, U va狸 nhi達旦u
base hi達炭m.. Ph叩n t脱鱈 co誰 ch脱誰a t脱狸 70 - 90 nucleotid, PTL
khoa鱈ng 23 000 - 30 000.
Co誰 棚t nh叩炭t 20 ph叩n t脱鱈 ARNt cho 20 loa短i acid amin (co誰
khoa鱈ng 56 loa短i ARNt kha誰c nhau trong m辰端t t達炭 ba狸o)
Ph叩n t脱鱈 ARNt g辰旦m co誰 4 nha誰nh ch棚nh va狸 m辰端t nha誰nh
phu短 va狸 co誰 h巽nh dang nh脱 m辰端t la誰 che鱈 ba:
+ Nha誰nh ti達炭p nh叩短n acid amin: k達炭t thu誰c b奪鱈i
b辰端 ba CCA (chi達旦u 5- 3)
+ Nha誰nh 但辰炭i ma樽: mang ba nucleotid 但辰炭i ma樽,
giu誰p nh叩短n ra ma樽 ba nucleotid t脱奪ng 脱誰ng tr達n ARNm la狸m
khu辰n.
+ Nha誰nh D (ch脱誰a nhi達旦u Dihydrouridin)
+ Nha誰nh T C co誰 ch脱誰a Thymidin, Pseudouridin va狸
Cytidin.
144
12. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Ngoa狸i ra co狸n co誰 m辰端t nho誰m phu短 , giu誰p ta ph叩n bi達短t
ca誰c nho誰m ARNt..
-
H巽nh 7.14. C叩炭u tru誰c ph叩n t脱鱈 ARN t
ARN r: li達n k達炭t v奪誰i protein ta短o tha狸nh ribosom la狸 n奪i
t辰淡ng h奪端p protein. ARN r la狸 m辰端t s奪端i polynucleotid
kh辰ng vo狸ng co誰 nhi達旦u khu誰c cu辰端n, ch脱誰a khoa鱈ng 100 1500 nucleotid (H巽nh 7.15).
E25
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o
U
U G
A
G
U G U UU U A U U G G C U
G C
G
U G
U
C G G UC U
U
A G
C
GU G A GG U UG A U U U
U
A
C G A
AA
A U
A U
G
U A U U UGGG
A G
A U
U U UC A
G U
U U
G C
A U
U GG G G
G U
C U
U
C
U
A UU
U
U
UUG
G
G
G U
G
G
U
U
U
G
UU
U
A
GG A
GGA
E26
Fasciola hepatica
E23
D18
E24
D19
E28
E22
G2
F1
E21
D13
E18
D12
D11
D21
IV
G16
D5
V
II
D6
D2
D10
G1
D1
3'
D7
H2
G17
G20
VI
5'
G18
G19
C1
I
H巽nh 7.15. C叩炭u ta短o ARN r
145
13. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Ribosom cu鱈a loa狸i co誰 vu誰 co誰 PTL khoa鱈ng 4,2x10 6 co誰
h達短 s辰炭 l探ng 80S,g辰旦m 2 ba誰n 但奪n v谷: ba誰n 但奪n v谷 l奪誰n 60S va狸
ba誰n 但奪n v谷 nho鱈 40S.
- ARNsn: la狸 nh脱樽ng ARN 但脱奪端c t巽m th叩炭y 奪鱈 t達炭 ba狸o
nh叩n th叩短t, co誰 nhi達旦u trong nh叩n t達炭 ba狸o, tham gia trong c奪
ch達炭 c探t bo鱈 但oa短n intron trong vi達短c hoa狸n thi達短n ARNm.
V. S KHU TRU AN TRON G T BAO
- 但辰端ng v叩短t, th脱短c v叩短t, vi khu叩淡n t達炭 ba狸o ch脱誰a ca鱈
ARN va狸 ADN.
ADN: Chu鱈 y達炭u 奪鱈 trong nh叩n, ty th達淡, ha短t di達短p lu短c.
ARN: Co誰 trong nh叩n, ha短t nh叩n, ribosom, ba狸o tr脱奪ng,
ty th達淡.
- virus g叩y b達短nh kha鱈m thu辰炭c la誰, polio: t達炭 ba狸o ch竪
ch脱誰a ARN.
- th脱短c khu叩淡n th達淡 adenovirus: t達炭 ba狸o ch竪 ch脱誰a
ADN.
.
.
146
14. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
CHUYN
PHN 2.
NUCLEIC
HOA
ACID
I. S THOAI HOA
1. S脱 短 thoa誰i ho誰a chun g
mono n u c l e o t i d
cu鱈a acid nucleic 但達炭 n
ca誰c m辰 但辰端ng v叩短t acid nucleic 但脱奪端c thu鱈y ph叩n
tha狸nh mononucleotid nh奪狸 enzym nuclease c探t 但脱誰t li達n k達炭t
phosphodieste cu鱈a polynucleotid.
Nuclease g辰旦m 02 loa短i:
Ribonuclease (RNase) thu鱈y ph叩n ARN.
Deoxyribonuclease (DNase) thu鱈y ph叩n ADN.
M辰湛i loa短i la短i ph叩n la狸m: Exonuclease va狸 endonuclease
tu狸y theo ca誰ch thu鱈y ph叩n.
2. S脱 短 thoa誰i ho誰a cu鱈a mon o n u cl e o t i d
D脱奪誰i ta誰c du短ng cu鱈a nucleotidase, nucleotid b谷
thu鱈y ph叩n tha狸nh nucleosid va狸 H 3 PO4 va狸 v奪誰i ta誰c du短ng cu鱈a
nucleosidase, nucleosid b谷 thu鱈y ph叩n tha狸nh base nit奪 va狸
pentose (H巽nh 7.16).
Nucleoprot ein
Prot ein t hu叩旦n
(Hist on prot am in)
Acid nucleic
(Polynucleot id)
Nuclease
Mononucleot id
Nucleot idase
phosphoric
Nucleosid
Acid
Nucleosidase
Base nit 奪
Pyrim idin)
Pent ose
( Ribose, Desoxy ribose)
(Purin,
H巽nh 7.16. Ca誰c sa鱈n ph叩淡m cu鱈a s脱短 t huy鱈 ph叩n acid
nucleic
147
15. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
H 3 PO4 但脱奪端c s脱鱈 du短ng cho qua誰 tr巽nh phosphoryl ho誰a
ho短c 但a狸o tha鱈i d脱奪誰i da短ng mu辰炭i phosphat. Pentose thoa誰i
ho誰a theo 但脱奪狸ng chuy達淡n ho誰a cu鱈a glucid. Ca誰c base nit奪 thoa誰i
ho誰a cho sa鱈n ph叩淡m la狸 acid uric, ur達...
3. Thoa誰i ho誰a ca誰c bas e co誰 nit奪
3.1. Thoa誰i ho誰a ba s e loa短i purin
Adenin, guanin b谷 thu鱈y ph叩n tha狸nh hypoxanthin va狸
xanthin d脱奪誰i ta誰c du短ng cu鱈a adenase, guanase sau 但o誰 oxy
ho誰a tha狸nh acid uric d脱奪誰i ta誰c du短ng cu鱈a xanthin oxydase,
ngoa狸i ra adenosin cu樽ng b谷 kh脱鱈 amin b奪鱈i adenosin
desaminase ta短o inosin r辰旦i oxy ho誰a cho hypoxanthin va狸 cu辰炭i
cu狸ng la狸 acid uric (S奪 但辰旦 h巽nh 7.17).
Ade n o s i n
Gua ni n
NH2
Ade ni n
NH2
N
N
N
N
N
N
Ribos
e
Adenosin
N
H 2O
NH 3
O
N
Xant hi n
Adenase
NH 3
O
N
NH
N
H2N
H 2O
desaminase
HN
N
N
NH
H2O
Guanin
NH 3
O
N
Ribose
O
Nucleosidase
[ O]
N
HN
Ribose N
N
N
NH
N
N
O
Inosin
Hypo x a n t h i n
[O] OXanthinoxydase
HN
NH
Acid uric
O
O
NH
NH
H巽nh 7.17. S奪 但辰旦 thoa誰i hoa誰 base purin
3.2. Thoa誰i ho誰a loa短i ba s e pyri m i d i n
148
16. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Thoa誰i ho誰a ca誰c loa短i base pyrimidin xa鱈y ra chu鱈 y達炭u 奪鱈
gan va狸 ch脱a bi達炭t ro樽. S脱短 bi達炭n 但辰淡i cu鱈a uracil 奪鱈 m辰 但辰端ng
v叩短t va狸 m辰端t s辰炭 vi khu叩淡n 但脱奪端c m辰 ta鱈 theo s奪 但辰旦 sau (S奪
但辰旦 h巽nh 7.18).
H2O
N
HO
N
OH
OH
NH2
N 3
H
N
N
HO
N
HO
CH3
N
Uracil
Cytosin
Thymin
NADPHH +
NADPHH +
NADP +
NADP +
OH
N
CH2
N
HO
OH
CH2
N
N
HO
Dihydro Uracil
O
N
CH2
+H2O
HOOC
NH2
CH2
CH2
CH3
Dihydro Thimin
+H2O
HOOC
NH2
CH
O
N
CH
CH2
H
H
Ureido Propionat
H2O
Ureido isobutyrat
H2O
CO2 + NH3
Alanin
Amino isobutyrat
H巽nh 7.18. S奪 但辰旦 thoa誰i hoa誰 base
pyrimidin
II. TN G HP ACID NUCLEIC
1. T辰淡n g h奪端 p nucl e ot i d
1.1. T辰淡n g h奪端 p rib o n u c l e o t i d co誰 ba s e purin
Ng脱奪狸i ta 但a樽 xa誰c 但谷nh 但脱奪端c ca誰c nguy達n t辰炭 tr達n nh叩n
purin co誰 ngu辰旦n g辰炭c nh脱 sau, xem h巽nh 7.19.
149
CH3
17. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
CO2
C4,C5,N7: Glycin
Asp
N1
2
Formic
6
N
7
8
5
3 4
N
9
N
Formic
Glutamin
H巽nh 7.19. S奪 但辰旦 nguy達n li達短u t辰淡ng h奪端p ribonucleotid
co誰 base purin
Qua誰 tr巽nh t辰淡ng h奪端p g辰旦m 4 giai 但oa短n:
Giai 但oa短n 1: B探t 但叩旦u t脱狸 ribose 5 (P) 但脱奪端c
phosphoryl ho誰a ta短o tha狸nh 5 phosphoribosyl 1 pyrophosphat
(PRPP), sau 但o誰 g探m amin cu鱈a glutamin r辰旦i k達炭t h奪端p v奪誰i
glycin ta短o tha狸nh glycimamid ribosyl 5 (P) v奪誰i s脱短 tham gia
cu鱈a enzym amidotransferase va狸 nng l脱奪端ng do ATP cung
c叩炭p (H巽nh 7.20).
CH2O
O
C H2O
O
P
ATP
OH
ADP
P
O
Nucleotid phosphorylase
P
P
O H OH
OH O H
5'-Phosphoribosyl-1-pyrophosphat
(PRPP)
Ribose-5'- P
Gln
Amidotransferase
Glu
PPi
P
O
H2C
O
NH
C
O
OH O H
Glycinamid Ribosyl-5- P
P
C H2 NH2
ADP + Pi
Mg ++
H2N
ATP
O
H2C
O
NH2
O H OH
C H2 CO OH
Glycin
5-Phosphoribosylamin
H巽nh 7.20. T辰淡ng h奪端p glycinamid ribosyl 5 phosphat
150
18. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Giai 但oa短n 2: Ta短o nh叩n imidazol cu鱈a purin.
Glycimamid ribosyl 5 但脱奪端c fomyl ho誰a xu誰c ta誰c b奪鱈i
enzym transfomylase ta短o tha狸nh glycinamidribosyl 5 , r辰旦i
amin ho誰a va狸 但o誰ng vo狸ng ta短o tha狸nh aminoimidazol ribosyl 5
, ATP cung c叩炭p nng l脱奪端ng (H巽nh 7.21).
H
NH2
H2C
O
N
H-CHO
H2C
f10F.H 4
C
Transformylase
NH
5'- P
R
Glycinamid Ribosyl- P
5'-
C
C
O
NH
O
H
5'- P
R
FormylGlycinamid Ribosyl- P
5'Gln
ATP
Mg++
Glu
H
N
H2C
C
H2N
H2O
CH
H2C
C
C
O
NH
o誰ng vo狸ng
N
R
N
++
ATP,Mg
H2N
5'- P
H
R 5'- P
FormylGlycinamidin Ribosyl- P
5'-
Aminoimidazol Ribosyl- P
5'-
H巽nh7.21. Ta短o nh叩n imidazol cu鱈a purin
Giai 但oa短n 3: Ta短o nh叩n pyrimidin cu鱈a purin va狸 s脱短 h巽nh
tha狸nh IMP: Amidimidazol ribosyl 5 但脱奪端c carboxyl ho誰a r辰旦i
k達炭t h奪端p v奪誰i aspartat ta短o tha狸nh 5 amino 4 succino imidazol
ribonucleotid, ta誰ch fumrat r辰旦i fomyl ho誰a va狸 但o誰ng vo狸ng ta短o
acid inosinic (IMP) (H巽nh 7.22).
Giai 但oa短n 4: Chuy達淡n acid inosinic tha狸nh acid adenylic
(AMP) va狸 acid guanylic (GMP) (H巽nh 7.23).
-
Ta短o acid Adenylic:
Acid inosinic ng脱ng tu短 v奪誰i acid aspartic ta短o tha狸nh
succino adenin nucleotide, pha鱈n 脱誰ng c叩旦n nng l脱奪端ng t脱狸
s脱短 ph叩n hu鱈y GTP. Sau 但o誰 ta誰ch acid fumaric 但達淡 ta短o tha狸nh
AMP.
151
19. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
-
Ta短o acid Guanylic:
Acid inosinic b谷 xy ho誰a 奪鱈 vj tr棚 C2
cu鱈a purin, sau 但o誰 g探n
amin 但達淡 ta短o tha狸nh GTP. Nng l脱奪端ng 但脱奪端c cung c叩炭p t脱狸 s脱短
ph叩n gia鱈i ATP.
H
H2N
C N
C
HOOC
CO 2 +Asp
++
Biotin ATP, Mg
CH
CH2
Kinosynthetase
N
HC
5'- P
R
O
HOOC
C
C N
HN
C N
H2N
CH
5'- P
R
Adenylo-Succinase
Aminoimidazol Ribosyl-5'- P
Fumarat
O
C
H2N
O
CH
N
H
O
C
N
C N
R
10
f FH
4
CH
5'- P
C
H-CHO
H2N
H2N
Transformylase
5-Formamido-4-carboxamid
imidazol ribosyl-5'- P
C
C
N
N
C N
CH
R
5'- P
5-Amino-4-carboxamid
imidazol ribosyl-5'- P
O
HN
C
C N
C N
CH
5'- P
R
Inosin-5'-monophosphat
(IMP)
H巽nh 7.22. Ta短o nh叩n pyrimidin cu鱈a purin
Ngoa狸i qua誰 tr巽nh tr達n ca誰c mononucleotid co狸n 但脱奪端c
h巽nh tha狸nh t脱狸 ca誰c base t脱短 do qua k達炭t h奪端p v奪誰i PRPP
(H巽nh 7.23).
Hypoxanthin + PRPP
acid inosinic + PPi
Hypoxanthin Phosphoribosyl transferase
Guanin + PRPP
acid guanylic +
PPi
Guanin Phosphoribosyl transferase
Adenin + PRPP
(GMP)
acid adenylic +
PPi
Adenin Phosphoribosyl transferase
(AMP)
Adenosin + ATP
adenylic + PPi
Nucleosid - Kinase
(AMP)
H巽nh 7.23. T辰淡ng h奪端p mononucleotid t脱狸 ca誰c base t脱短 do
152
acid
20. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Ca誰c pha鱈n 脱誰ng cu鱈a giai 但oa短n 4:
HOOC
O
HN
C
C
C
C N
N
Asp
N
HN
GTP, Mg ++
Adenylosuccinat
C
synthetase
5'- P
Inosin-5'-monophosphat
(IMP)
[O]
C
N
C
O
N
C
HN
N
C
CH
N
R
C
N
C
C
N
CH
N
5'- P
Adenosin-5'-monophosphat
(AMP)
Acid adenylat
O
HN
H2N
Fumarat
R
5'- P
Xanthosin-5'-monophosphat
Gln
ATP
Glu
CH
NH3
O
C
C N
Adenylo succinase
+
NADH+H
HN
N
C
5'- P
R
Succinoadenin nucleotid
NAD+
C
COOH
NH
H2O
CH
R
CH CH2
C
C
N
C
C
N
CH
N
R
5'- P
Guanosin-5'-monophosphat
(GMP)
H巽nh 7.24. Chuy達淡n acid inosinic tha狸nh AMP va狸
GMP
1.2. S 脱 短
t辰淡n g
h奪端 p
pyri m i d i n g辰 旦 m hai giai 但oa短 n
rib o n u c l e o t i d
co誰
ba s e
Giai 但oa短n I: Ta短o orotat:
Nguy達n li達短u 但叩旦u ti達n la狸 carbamyl va狸 aspartat v奪誰i
s脱短 xu誰c ta誰c cu鱈a aspartat transcarbamylase se樽 ta短o tha狸nh
carbamyl aspartat, ch叩炭t na狸y 但o誰ng vo狸ng ta短o tha狸nh
dihydroorotat xu誰c ta誰c b奪鱈i dihydroorotat r辰旦i oxy ho誰a ta短o
tha狸nh orotat (H巽nh 7.25).
Giai 但oa短n II: Ta短o tha狸nh base pyrimidin va狸 nucleotid co誰
base pyrimidin:
Orotat g探n v奪誰i ribose 5 do PRPP cung c叩炭p v奪誰i s脱短
xu誰c ta誰c cu鱈a orotydilic pyrophosphorylase ta短o tha狸nh oritidin
5 r辰旦i b谷 kh脱鱈 carboxyl ta短o tha狸nh uridin monophosphat
(UMP) xu誰c ta誰c b奪鱈i enzym orotidin 5 decarboxylase (H巽nh
7.26).
153
21. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
O
O
HO C
Aspartat
NH2
Transcarbamylase
HOOC
H2N
CH2
+
C
O
C
P
COOH
H2N
Carbamyl phosphat
C
O
Pi
C
N
COOH
H
Carbamyl aspartat
Aspartat
H2O
Dihydro Orotase
O
O
H
C
N
C
N
O
+
NADH + H+ NAD
C
H
H
C
Dihydro Orotat
Dehydrogenase
COOH
C
N
C
N
O
COOH
H
H
Orotat
Dihydro Orotat
H巽nh 7.25. Ta短o orotat t脱狸 carbamyl va狸 aspartat
O
O
H
C
N
C
PRPP
C
N
O
H
PPi
C
N
C
Orotidylic
COOH Pyrophosphorylase O
H
UTP
UDP
C
Reductase
ADP+Pi
dUDP
C
CH3
N
R
C
5
dUMP
P
P
P
N
C
ATP
NH2
O
P
5
Orotidin-5'-phosphat
Orotidylat
Decarboxylase
N
COOH
R
H
Orotat
NH3
C
N
O
CO 2
O
C
N
R
5'
P
Uridin -5'-monophosphat
(UMP)
Uridylat
O
Thymidin
Synthetase
H
N
C
Cytidin-5'-monophosphat
(CTP)
C
O
C
N
CH3
C
dR 5 ' P
Deoxythymidin-5'-monophosphat
(dTMP)
H巽nh 7.26. Ta短o nucleotid co誰 base pyrimidin
154
22. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
Uridin monophosphat (UMP) phosphonyl ho誰誰a 2 l叩旦n ta短o tha狸nh
uridin triphosphat (UTP), UTP amin ho誰a ta短o tha狸nh cytidin
triphosphat (CTP).
1.3. T辰淡n g h奪端 p d e o x y r i b o n u c l e o t i d
Deoxyribonucleotid 但脱奪端c h巽nh tha狸nh b奪鱈i qua誰 tr巽nh kh脱鱈 oxy
tr脱短c ti達炭p 奪鱈 C2 cu鱈a ribose cu鱈a ca誰c ribonucleotid:
(ADP, GDP, UDP, CDP)
(dADP, dGDP, dUDP, dCDP)
Ribonucleosid di(P) reductase
(Enzym c坦 vit B1, B2)
ATP
ADP
NDP
dNTP
Nucleosid diphosphat kinase
H巽nh 7.27. T辰淡ng h奪端p deoxyribonucleotid
T辰淡ng h奪端p acid deoxythymidylic (dTTP), dTTP kh辰ng co誰
ribonucleotid t脱奪ng 脱誰ng, 但脱奪端c t辰淡ng h奪端p t脱狸 UDP nh脱 sau:
Phosphoryl ho誰a.
UDP
dUDP
dTTP
2. T辰淡n g h奪端 p ADN:
dUMP
dTMP
2.1. S脱短 ta誰i ba鱈n ba鱈o t辰旦n cu鱈a ADN
D脱短a tr達n c叩炭u tru誰c cu鱈a Watson va狸 Crick th巽 m辰湛i s奪端i cu鱈a
ph叩n t脱鱈 ADN xo探m ke誰p 但脱奪端c du狸ng la狸m khu辰n 但達淡 t辰淡ng h奪端p
m辰端t s奪端i b辰淡 sung theo quy lu叩短t 但辰i base 但達淡 ta短o 2 ph叩n t脱鱈 ADN
con, m辰端t trong hai s奪端i na狸y la狸 s奪端i cu鱈a ADN me短.
Enzym xu誰c ta誰c pha鱈n 脱誰ng t辰淡ng h奪端p la狸 ADN polymerase (I,
II, III). ADN polymerase I xu誰c ta誰c g探n mononucleotid,
mononucleotid va狸o nho誰m OH 奪鱈 v谷 tr棚 3 cu鱈a ADN m辰旦i 但達淡 ke誰o
da狸i theo h脱奪誰ng 5 - 3.
Ppi
(dNMP) n
+
ADN m 辰旦i, Mg + +
dNTP
(dNMP)
Enzym
dNMP: deoxyribonucleot id 5m ono
dNTP: deoxyribonucleot id 5 t ri
155
n + 1
+
24. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
H巽nh 7.28b. T辰淡ng h奪端p ADN
2.2. S脱短 s脱鱈a ch脱樽a ADN
Ca誰c th脱奪ng t辰淡n co誰 th達淡 xa鱈y ra tr達n ADN:
- Do sai l叩旦m khi ke短p 但辰i trong qua誰 tr巽nh ta誰i ba鱈n
- Do y達炭u t辰炭 ngoa短i lai: nhi達短t 但辰端, tia t脱鱈 ngoa短i, tia X
Ca誰c h達短 th辰炭ng s脱鱈a ch脱樽a: do ha狸ng loa短t enzym, protein:
- Ke短p 但辰i
- C探t base
- C探t nucleotid
-S脱鱈a ch脱樽a tr脱短c ti達炭p
3. T辰淡n g h奪端 p ARN
3.1. Qua誰 tr巽nh t辰淡ng h奪端p
Enzym t辰淡ng h奪端p ARN la狸 ARN polymerase:
- ARN poly m e r a s e phu 短 th u 辰 端 c ARN (re p lica s e : enzy m
ta誰i ba鱈n). ARN m奪誰i 但脱奪端c t辰淡ng h奪端p d脱短a tr達n khu辰n ARN ta誰c
du短ng cu鱈a ARN polymerase, enzym xu誰c ta誰c:
ARN m辰旦i, Mg + +
n 1 ATP + n 2 GTP + n 3 CTP + n 4 UTP
[(AMP)n 1 - (GTP)n 2
- (CMP)n 3 - (UMP)n 4 ]
ARN polymerase
+ (n 1 + n 1 + n 1 +
n 1 ) PPi
叩y la狸 s脱短 nh叩n 但辰i ARN cu鱈a virus trong t達炭 ba狸o chu鱈
trong qua誰 tr巽nh nhi達湛m tru狸ng, ARN (+) cu鱈a virus du狸ng la狸m
khu辰n 但達淡 t辰淡ng h奪端p s奪端i ARN (-) b辰淡 sung va狸 xo探n ke誰p v奪誰i
ARN (+) r辰旦i t脱狸 ARN (-) la短i la狸m khu辰n t辰淡ng h奪端p ARN (+)
157
25. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
cu鱈a virus.
+
+
+
+
+
ARN( +)
Xo探 n ke誰p
ARN( +)
H巽nh
S脱短 nh叩n 但辰i cu鱈a virus trong t達炭 ba狸o chu鱈
7.29:
- ARN poly m e r a s e phu 短 th u 辰 端 c ADN (tra n s c r i p t a s e :
enzy m sao ch e誰 p ). S脱短 t辰淡ng h奪端p ribonucleotid 5 monophosphat
trong ARN la狸 m辰端t qua誰 tr巽nh sao che誰p b奪鱈i v巽 ca誰c th辰ng tin di
truy達旦n ch脱誰a trong ADN 但脱奪端c sao che誰p sang ARN.
ARN polymerase xu誰c ta誰c t辰淡ng h奪端p ARN cu鱈a t達炭 ba狸o (ARN r ,
ARNt , ARNm ) t脱狸 ca誰c ribonucleotid triphosphat gia鱈i pho誰ng
pyrophosphat, pha鱈n 脱誰ng c叩旦n ADN la狸m khu辰n, ca誰c base cu鱈a ARN
t辰淡ng h奪端p b辰淡 sung v奪誰i m辰端t trong hai chu辰湛i cu鱈a ADN va狸 pha誰t
tri達淡n theo h脱奪誰ng 5 - 3 (H巽nh 7.30).
ADN, Mg + +
n 1 ATP + n 2 GTP + n 3 CTP + n 4 UTP
MP)n 1 - (GMP)n 2 - (CMP)n 3 (UMP)n 4 ]
enzym
+ (n 1 + n 2 + n 3 + n 4 )Ppi
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26. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic
H巽nh 7.31. Sao che誰p ARN t脱狸 khu辰n AND
3.2. Ch叩炭t 脱誰c ch達炭 s脱短 t辰淡ng h奪端p ARN
Kha誰ng sinh va狸 但辰端c t辰炭 脱誰c ch達炭 ARN- Polymerase
- Amanitin 脱誰c ch達炭 ARN polymerase 奪鱈 t達炭 ba狸o co誰 nh叩n (但叩y la狸 c奪
ch達炭 nhi達湛m 但辰端c cu鱈a n叩炭m 但辰端c Amanita phalloides)
- Kha誰ng sinh Rifampicin 脱誰c ch達炭 ARN polymerase cu鱈a bacteria,
Rifampicin g探n va狸o chu辰湛i b達ta, 但脱奪端c du狸ng 但達淡 但i達旦u tr谷 lao
3.3. S脱短 hoa狸n thi達短n ARN sau sao che誰p
Ca誰c ARN sau khi 但脱奪端c t辰淡ng h奪端p theo qua誰 tr巽nh sao che誰p
la狸 nh脱樽ng ph叩n t脱鱈 ARN s奪 c叩炭p, co狸n go端i la狸 ph叩n t脱鱈 ti達旦n ARN.
Ca誰c ph叩n t脱鱈 na狸y pha鱈i qua m辰端t qua誰 tr巽nh hoa狸n thi達短n 但達淡 ta短o
tha狸nh ca誰c ARN tr脱奪鱈ng tha狸nh hay ARN hoa狸n thi達短n. S脱短 hoa狸n
thi達短n ca誰c ARN g辰旦m ca誰c giai 但oa短n:
- C探t b奪誰t 但oa短n 奪鱈 但叩旦u hay 奪鱈 gi脱樽a
- N辰炭i ca誰c 但oa短n co狸n la短i v奪誰i nhau
- Bi達炭n 但辰淡i m辰端t s辰炭 base trong chu辰湛i
- Th達m 但oa短n mu樽 va狸 但oa短n Poly A v奪誰i ARNm 奪鱈 t達炭 ba狸o co誰
nh叩n
3.4. Sao che誰p ng脱奪端c ADN t脱狸 ARN/virus
M辰端t va狸i ARN virus 奪鱈 trong t辰淡 ch脱誰c 但辰端ng v叩短t tham gia
tr脱短c ti達炭p va狸o s脱短 t辰淡ng h奪端p ADN go端i la狸 sao che誰p ng脱奪端c:
M辰端t s辰炭 Retrovirus g叩y ra ung th脱
Trong nhi達湛m tru狸ng, b辰端 gen tr達n chu辰湛i 但奪n ARN virus ( co誰
khoa鱈ng 10 000 nucleotid) va狸 enzym 但i va狸o t達炭 ba狸o chu鱈. Enzym sao
che誰p ng脱奪端c xu誰c ta誰c s脱短 t辰淡ng h奪端p ADN b辰淡 sung tr達n ARN
virus ta短o tha狸nh ph叩n t脱鱈 lai ARN-ADN. Ph叩n t脱鱈 na狸y sa誰t nh叩短p
va狸o ph叩n t脱鱈 ADN cu鱈a t達炭 ba狸o chu鱈. B嘆ng c奪 ch達炭 na狸y m辰端t s辰炭
Retrovirus g叩y ra ung th脱 nh脱 Rous sarcom virus (co狸n go端i la狸
Avian Sarcom Virus).
III. RI LOAN CHUY N HOA ACID NUCLEIC
B巽nh th脱奪狸ng acid uric trong ma誰u khoa鱈ng 3 - 7mg/100ml (190420 袖mol/l), trong n脱奪誰c ti達淡u khoa鱈ng 0,3 - 0,8g/24gi奪狸, 棚t thay 但辰淡i
trong cu狸ng m辰端t ng脱奪狸i nh脱ng thay 但辰淡i theo ch達炭 但辰端 n, n
nhi達旦u purin (gan, th叩短n...) l脱奪端ng acid uric trong n脱奪誰c ti達淡u tng.
Trong
tr脱奪狸ng
h奪端p
thi達炭u
enzym
t辰淡ng
h奪端p
nucleotidHypoxantin, Guanin hay Adenin Phosphoribosyl Transferase,
ca誰c base purin tng thoa誰i ho誰a ta短o acid uric, do 但o誰 acid uric trong
ma誰u tng.
Trong b達短nh tng ba短ch c叩旦u, b達短nh goutte l脱奪端ng acid uric
trong ma誰u tng 7 - 8mg/100ml, 但短c bi達短t trong b達短nh goutte
159