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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
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
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)
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
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
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
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
Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic

hai h脱奪誰ng ng脱奪端c nhau quanh m辰端t tru短c chung (H巽nh 7.10).
- M辰湛i nucleotid n嘆m trong m短t ph坦ng th坦ng go誰c v奪誰i
chu辰湛i polynucleotid, hai chu辰湛i mononucleotid li達n k達炭t v奪誰i nhau
b嘆ng nh脱樽ng li達n k達炭t hydro gi脱樽a 但辰i base:
A li達n k達炭t v奪誰i T b嘆ng 2 li達n k達炭t hydro.
G li達n k達炭t v奪誰i C b嘆ng 3 li達n k達炭t hydro.

H巽nh 7.10. M辰 h巽nh c叩炭u tru誰c b叩短c 2 cu鱈a ADN theo Watson
va狸 Crick
- S脱短 h巽nh tha狸nh li達n k達炭t gi脱樽a 但辰i base nh脱 v叩短y go端i la狸
quy lu叩短t 但辰i base b辰淡 sung, th脱誰 t脱短 ca誰c base trong m辰端t s奪端i co誰
th達淡 kha誰c nhau nh脱ng s奪端i th脱誰 2 pha鱈i co誰 t棚nh ch叩炭t b辰淡 sung,
nucleotid na狸y ca誰ch nucleotid kia 0,34 nm, m辰湛i vo狸ng xo探n da狸i 3,4
nm va狸 g辰旦m 10 但辰i base. V達旦 sau na狸y, k達炭t qua鱈 但o 但a短t cho th叩炭y
r嘆ng m辰湛i chu ky狸 xo探n da狸i 3,6 nm va狸 ch脱誰a khoa鱈ng 10,5
mononucleotid.
- Do nguy達n t探c b辰淡 sung n達n ty鱈 l達短:
A/T = G/C = 1
A+T
Ty鱈 l達短
kha誰c nhau tu狸y loa短i va狸 tu狸y c奪 quan.
G+ C

A + T>G + C: th脱奪狸ng th叩炭y 奪鱈 但辰端ng v叩短t co誰 vu誰.
A + T<G + C: th脱奪狸ng th叩炭y 奪鱈 vi sinh v叩短t.
- Co誰 th達淡 h巽nh t脱奪端ng m辰湛i chu辰湛i polynucleotid g辰旦m 3 da鱈i:
141
Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic

Trong cu狸ng la狸 da鱈i base nit奪 li達n k達炭t v奪誰i base nit奪 da鱈i 但辰炭i
x脱誰ng b嘆ng li達n k達炭t hydro. K達炭 但達炭n la狸 da鱈i deoxyribose. Ngoa狸i
cu狸ng la狸 da鱈i acid phosphoric.
Khoa鱈ng ca誰ch gi脱樽a 2 deoxyribose 但辰炭i x脱誰ng la狸 1,1 nm.
Khoa鱈ng ca誰ch gi脱樽a 2 acid phosphoic la狸 2 nm.
- Ph叩旦n l奪誰n ADN g辰旦m 2 s奪端i xo探n ke誰p m奪鱈 ho短c vo狸ng,
nh脱ng cu樽ng co誰 m辰端t s辰炭 ca誰 bi達短t ADN ch竪 g辰旦m m辰端t s奪端i da短ng
vo狸ng nh脱 trong th脱短c khu叩淡n, m辰端t s奪端i da短ng m奪鱈 co誰 trong virus
但辰端ng v叩短t.
- ADN co誰 3 da短ng c叩炭u tru誰c kha誰c nhau: da短ng B co誰 ca誰c 但短c
但i達淡m c叩炭u tru誰c nh脱 tr達n; da短ng A t脱奪ng t脱短 nh脱 da短ng B nh脱ng
m辰湛i chu ky狸 xo探n ng探n h奪n ( 2,3 nm), g辰旦m 11 c短p base va狸
但脱奪狸ng k棚nh cu鱈a chu辰湛i xo探n l奪誰n h奪n; da短ng Z kha誰c bi達短t, co誰 2
chu辰湛i polynucleotid la短i v奪誰i nhau theo chi達旦u t脱狸 pha鱈i sang tra誰i,
chu ky狸 xo探n da狸i h奪n b嘆ng 3,7 nm, g辰旦m 12 c短p base, khoa鱈ng
ca誰ch m辰湛i c短p theo chi達旦u th坦ng 但脱誰ng la狸 0,38 nm.

Da短ng A

Da短ng B Da短ng Z

H巽nh 7.11. Ca誰c da短ng A,B va狸 Z cu鱈a ADN
1.3.T 棚 n h ch叩炭 t ADN
- T棚nh ch叩炭t bi達炭n t棚nh: ADN bi達炭n t棚nh khi 但un no誰ng, khi
thay 但辰淡i 但辰端t ng辰端t nhi達短t 但辰端 l達n t奪誰i 80 - 90 0 C, li達n k達炭t hydro b谷
pha誰 v奪樽, ADN ta誰ch 2 s奪端i, n達炭u la狸m la短nh v達旦 nhi達短t 但辰端 b巽nh
th脱奪狸ng, xo探n ke誰p la短i h巽nh tha狸nh. T棚nh ch叩炭t na狸y cu鱈a ADN
但脱奪端c go端i la狸 bi達炭n t棚nh thu叩短n ngh谷ch. ADN trong dung d谷ch pH7
co誰 但辰端 nh奪誰t cao, khi thay 但辰淡i pH qua誰 cao hay qua誰 th叩炭p ADN
cu樽ng b谷 bi達炭n t棚nh thu叩短n ngh谷ch.
- T棚nh ch叩炭t lai: hai ADN co誰 t脱狸 hai loa狸i kha誰c nhau co誰 tr叩短t
t脱短 s探p x達炭p t脱奪ng 但脱奪ng co誰 th達淡 lai ta短o v奪誰i nhau nh奪狸 va狸o
142
Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic

t棚nh ch叩炭t bi達炭n t棚nh thu叩短n ngh谷ch tr達n.
- Ca誰c nucleotid va狸 base co誰 nit奪 trong tha狸nh ph叩旦n cu鱈a ADN
co誰 th達淡 b谷 bi達炭n 但辰淡i hoa誰 ho端c (xem ph叩旦n chuy達淡n hoa誰).
2. C叩炭u tru誰c ARN
Acid ribonucleic cu樽ng la狸 polyme cu鱈a ca誰c ribonucletid. Ca誰c
base ch棚nh la狸 adenin, guanin, cytosin va狸 uracil. Ngoa狸i ra co狸n co誰
m辰端t s辰炭 d叩湛n xu叩炭t cu鱈a purin va狸 pyrimidin.
2.1. C叩炭 u tru誰c b叩短 c 1
ARN c叩炭u ta短o b奪鱈i nhi達旦u ribonucleotid tru狸ng h奪端p v奪誰i
nhau, ch脱誰a ca誰c base nit奪 A, G, C, U, ca誰c nucleotid li達n k達炭t
v奪誰i nhau b奪鱈i li達n k達炭t 3, 5 phosphodieste va狸 2, 3
phosphodieste 奪鱈 ma短ch nha誰nh (Hinh 7.12).

H巽nh 7.12. c叩炭u tru誰c b叩c1 cu鱈a ph叩n t脱鱈 ARN
2.2. C叩炭 u tru誰c b叩短 c 2
ARN ch竪 co誰 m辰端t s奪端i polynucleotid, ch竪 co誰 nh脱樽ng
但oa短n g叩旦n nhau m奪誰i li達n k達炭t v奪誰i nhau theo li達n k達炭t hydro
va狸 theo quy lu叩短t b辰淡 sung:
A - U b奪鱈i 2 li達n k達炭t hydro.
G - C b奪鱈i 3 li達n k達炭t hydro.
Ca誰 bi達短t cu樽ng co誰 ARN g辰旦m 2 s奪端i polynucleotid xo探n
va狸o nhau da短ng m奪鱈 nh脱 reovirus g叩y b達短nh cho loa狸i 但辰端ng
v叩短t co誰 vu誰.
2.3. Ca誰c loa短i ARN

143
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
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

UU
U U

A

G

U A
UU
UUU
G C
C UG A A
G
G U
A A U
U U
GGUAG
UUA
U A
G
U
U
U C G UAA
C
A U
A
G A
A
G G UC
U
U G
G
A
A
CC G C G
C
G
A
C C
A G U
CU A U
G
U U U
A
U G
U A U
U
A U
A A U
U
U A
G
A U
GGUG
G CC
UU
UC G
A
U
A UU
G
U
U
G
AG C
U
U G GA
G
U
UU U
U
UUC
UG C
G
UG
U A
A
UCC AUU
AAAAACA
G UA
G A UU A
AG UU UGU A U
U
A
U
U
G C
G CA
A GG U A A
U AUUUGU
U U U GC U
A
G
G C
GA
G
AUU
U
G
U U
U
U
UAA
A
U
U A
C
U A
G
G
C
G U
U
G
G U
C A GA
U G
U
G U
U
G
C
U G
C G
C
U
U
U A
U
U A
G C
A U
G C
C G
C
U
U A
A U
C G
U
GU AA
G C
U AU
U
G
U
U G
UU
U
U
A
G U GA
U G
UUGUGCU
U
C GU
G
G
U G
C
U A
G
A
A C UA G A A U G G
G C
G U
U A UU
G
U
G U
A
UU A
U
G A
GUC
G U G
U A
U U AU
G
U
CG U G
UCU G
G
A
U
U A
U
U
UA
A
U A
A G U AG
G
UA
C GU
U
A
G
C CGU
A U
U
C
U
A
U
U
G
U G
G U
G
UUA U
A
G
A
A
U
A
GC U
A UU A
G CG
A U
U A
G
G CC
A
A
U U
A
U A
U
U G
U
A
U UU
A
A U
C
G U
U AU
A UA
U
U G
G C
G
U A GA
A A U C U A CUC G
C G
AA U
G
C G
A
G
U
U
G UA
U
A
G CUG
A
G
C G AA
G
U
A U AU
UU G
A U
U
UA
U
C G U CUA U U
A
U
U
G
U
C G
U
G CG
U
G
A
AU CUGA
U
A
A
U
U
G
CU
A
A
G
U
A
G
CU
A
U
U
A
U
A
U
A
C
U G A AG GU GU
UA
U
U U A A A GACG G
U
U G U
C A
U G
UUUAG
U
A G
U U
U
U A
G G U U A U CU U C
U U
A U
G
C
G U
AU U
G A
U
G U
U A
U
C GG A C
G
G
U
G
U
U G
U
G
U
G
UAG
U
A
A
U AA
G
G
A
U A AGU
A
U
A
UG U
U
G
C
G
GG
U
G
U
U
G U
A
G GAA U UGA U
UG
G U
A
U G
AG CA
A
A U
C
C
A U C UC G
G UG
C
G U
G
C G
A
U
U G
G
UU C
G U
G
G
A G
U U
A
U G
G C
U
A UU
GA U
C
G U
UG
U
A
U
UA U
U G
G
G
U
UC C
A
C
U G
U
UC G
G U
U AU
G
U
A U
U G
G U
U
G G
o
U A
UC G G A
A U CU
U
U
U
U G
G
A
C
U
A
U
G
A U
A
C
UU G
A
G A
A
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
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
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
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
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
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
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
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
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
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
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

+
Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic

Ca誰c giai 但oa短n cu鱈a s脱短 ta誰i ba鱈n:
S奪 但辰旦 ta誰i ba鱈n d脱短a va狸o s脱短 th脱短c nghi達短m tr達n E.Coli nh脱
sau:
- Nh叩短n di達短n 但i達淡m b探t 但叩旦u: nhi達旦u protein tham gia s脱短
nh叩短n di達短n 但i達淡m b探t 但叩旦u giu誰p cho primase t辰淡ng h奪端p ARN
m辰旦i.
- M奪鱈 vo狸ng xo探n ke誰p ADN 但脱奪端c xu誰c ta誰c b奪鱈i enzym
helicase, n奪i hai s奪端i 但脱奪端c ta誰ch ra go端i la狸 cha短c ba ta誰i ba鱈n.
- Ta短o ARN m辰旦i, primase g探n va狸o 但i達淡m b探t 但叩旦u xu誰c ta誰c
t辰淡ng h奪端p ARN m辰旦i b辰淡 sung v奪誰i ADN.
- Ta短o ADN.
* M辰端t s奪端i 但脱奪端c t辰淡ng h奪端p li達n tu短c theo h脱奪誰ng cu鱈a
cha短c ba ta誰i ba鱈n (5 - 3) xu誰c ta誰c b奪鱈i enzym polymerase III.
* S奪端i kia t辰淡ng h奪端p kh辰ng li達n tu短c, s奪端i na狸y g辰旦m
nh脱樽ng 但oa短n khoa鱈ng 1000 - 2000 nucleotid go端i la狸 但oa短n okazaki,
m辰湛i 但oa短n b探t 但叩旦u b嘆ng m辰端t m叩湛u ARN m辰旦i r辰旦i t辰淡ng h奪端p
ke誰o da狸i b奪鱈i ADN polymerase III, sau 但o誰 ARN m辰旦i 但脱奪端c ta誰ch ra
b奪鱈i enzym exonuclease, polynurase I xu誰c ta誰c t辰淡ng h奪端p 但oa短n
ADN thi達炭u, ca誰c 但oa短n Okazaki la短i 但脱奪端c n辰炭i li達旦n nh奪狸 xu誰c ta誰c
cu鱈a ADN ligase (H巽nh 7.28).

H巽nh 7.28a. T辰淡ng h奪端p ADN

156
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
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

158
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
Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic

但辰旦ng th奪狸i v奪誰i s脱短 tng n辰旦ng 但辰端 acid uric trong ma誰u va狸 n脱奪誰c
ti達淡u, co誰 s脱短 l探ng 但o端ng tinh th達淡 urat 奪鱈 su短n, bao g叩n, tu誰i nha狸y
cu鱈a ca誰c kh奪誰p, 但辰i khi co狸n co誰 trong th叩短n, da va狸 c奪. Xung quanh
urat k達炭t tinh la狸 t辰淡 ch脱誰c vi達m h巽nh ca誰c ha短t goutte bao quanh
m辰 ch達炭t, th脱奪狸ng g短p 奪鱈 ca誰c kh奪誰p g叩y vi達m kh奪誰p ma樽n t棚nh.

160

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  • 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
  • 8. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic hai h脱奪誰ng ng脱奪端c nhau quanh m辰端t tru短c chung (H巽nh 7.10). - M辰湛i nucleotid n嘆m trong m短t ph坦ng th坦ng go誰c v奪誰i chu辰湛i polynucleotid, hai chu辰湛i mononucleotid li達n k達炭t v奪誰i nhau b嘆ng nh脱樽ng li達n k達炭t hydro gi脱樽a 但辰i base: A li達n k達炭t v奪誰i T b嘆ng 2 li達n k達炭t hydro. G li達n k達炭t v奪誰i C b嘆ng 3 li達n k達炭t hydro. H巽nh 7.10. M辰 h巽nh c叩炭u tru誰c b叩短c 2 cu鱈a ADN theo Watson va狸 Crick - S脱短 h巽nh tha狸nh li達n k達炭t gi脱樽a 但辰i base nh脱 v叩短y go端i la狸 quy lu叩短t 但辰i base b辰淡 sung, th脱誰 t脱短 ca誰c base trong m辰端t s奪端i co誰 th達淡 kha誰c nhau nh脱ng s奪端i th脱誰 2 pha鱈i co誰 t棚nh ch叩炭t b辰淡 sung, nucleotid na狸y ca誰ch nucleotid kia 0,34 nm, m辰湛i vo狸ng xo探n da狸i 3,4 nm va狸 g辰旦m 10 但辰i base. V達旦 sau na狸y, k達炭t qua鱈 但o 但a短t cho th叩炭y r嘆ng m辰湛i chu ky狸 xo探n da狸i 3,6 nm va狸 ch脱誰a khoa鱈ng 10,5 mononucleotid. - Do nguy達n t探c b辰淡 sung n達n ty鱈 l達短: A/T = G/C = 1 A+T Ty鱈 l達短 kha誰c nhau tu狸y loa短i va狸 tu狸y c奪 quan. G+ C A + T>G + C: th脱奪狸ng th叩炭y 奪鱈 但辰端ng v叩短t co誰 vu誰. A + T<G + C: th脱奪狸ng th叩炭y 奪鱈 vi sinh v叩短t. - Co誰 th達淡 h巽nh t脱奪端ng m辰湛i chu辰湛i polynucleotid g辰旦m 3 da鱈i: 141
  • 9. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic Trong cu狸ng la狸 da鱈i base nit奪 li達n k達炭t v奪誰i base nit奪 da鱈i 但辰炭i x脱誰ng b嘆ng li達n k達炭t hydro. K達炭 但達炭n la狸 da鱈i deoxyribose. Ngoa狸i cu狸ng la狸 da鱈i acid phosphoric. Khoa鱈ng ca誰ch gi脱樽a 2 deoxyribose 但辰炭i x脱誰ng la狸 1,1 nm. Khoa鱈ng ca誰ch gi脱樽a 2 acid phosphoic la狸 2 nm. - Ph叩旦n l奪誰n ADN g辰旦m 2 s奪端i xo探n ke誰p m奪鱈 ho短c vo狸ng, nh脱ng cu樽ng co誰 m辰端t s辰炭 ca誰 bi達短t ADN ch竪 g辰旦m m辰端t s奪端i da短ng vo狸ng nh脱 trong th脱短c khu叩淡n, m辰端t s奪端i da短ng m奪鱈 co誰 trong virus 但辰端ng v叩短t. - ADN co誰 3 da短ng c叩炭u tru誰c kha誰c nhau: da短ng B co誰 ca誰c 但短c 但i達淡m c叩炭u tru誰c nh脱 tr達n; da短ng A t脱奪ng t脱短 nh脱 da短ng B nh脱ng m辰湛i chu ky狸 xo探n ng探n h奪n ( 2,3 nm), g辰旦m 11 c短p base va狸 但脱奪狸ng k棚nh cu鱈a chu辰湛i xo探n l奪誰n h奪n; da短ng Z kha誰c bi達短t, co誰 2 chu辰湛i polynucleotid la短i v奪誰i nhau theo chi達旦u t脱狸 pha鱈i sang tra誰i, chu ky狸 xo探n da狸i h奪n b嘆ng 3,7 nm, g辰旦m 12 c短p base, khoa鱈ng ca誰ch m辰湛i c短p theo chi達旦u th坦ng 但脱誰ng la狸 0,38 nm. Da短ng A Da短ng B Da短ng Z H巽nh 7.11. Ca誰c da短ng A,B va狸 Z cu鱈a ADN 1.3.T 棚 n h ch叩炭 t ADN - T棚nh ch叩炭t bi達炭n t棚nh: ADN bi達炭n t棚nh khi 但un no誰ng, khi thay 但辰淡i 但辰端t ng辰端t nhi達短t 但辰端 l達n t奪誰i 80 - 90 0 C, li達n k達炭t hydro b谷 pha誰 v奪樽, ADN ta誰ch 2 s奪端i, n達炭u la狸m la短nh v達旦 nhi達短t 但辰端 b巽nh th脱奪狸ng, xo探n ke誰p la短i h巽nh tha狸nh. T棚nh ch叩炭t na狸y cu鱈a ADN 但脱奪端c go端i la狸 bi達炭n t棚nh thu叩短n ngh谷ch. ADN trong dung d谷ch pH7 co誰 但辰端 nh奪誰t cao, khi thay 但辰淡i pH qua誰 cao hay qua誰 th叩炭p ADN cu樽ng b谷 bi達炭n t棚nh thu叩短n ngh谷ch. - T棚nh ch叩炭t lai: hai ADN co誰 t脱狸 hai loa狸i kha誰c nhau co誰 tr叩短t t脱短 s探p x達炭p t脱奪ng 但脱奪ng co誰 th達淡 lai ta短o v奪誰i nhau nh奪狸 va狸o 142
  • 10. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic t棚nh ch叩炭t bi達炭n t棚nh thu叩短n ngh谷ch tr達n. - Ca誰c nucleotid va狸 base co誰 nit奪 trong tha狸nh ph叩旦n cu鱈a ADN co誰 th達淡 b谷 bi達炭n 但辰淡i hoa誰 ho端c (xem ph叩旦n chuy達淡n hoa誰). 2. C叩炭u tru誰c ARN Acid ribonucleic cu樽ng la狸 polyme cu鱈a ca誰c ribonucletid. Ca誰c base ch棚nh la狸 adenin, guanin, cytosin va狸 uracil. Ngoa狸i ra co狸n co誰 m辰端t s辰炭 d叩湛n xu叩炭t cu鱈a purin va狸 pyrimidin. 2.1. C叩炭 u tru誰c b叩短 c 1 ARN c叩炭u ta短o b奪鱈i nhi達旦u ribonucleotid tru狸ng h奪端p v奪誰i nhau, ch脱誰a ca誰c base nit奪 A, G, C, U, ca誰c nucleotid li達n k達炭t v奪誰i nhau b奪鱈i li達n k達炭t 3, 5 phosphodieste va狸 2, 3 phosphodieste 奪鱈 ma短ch nha誰nh (Hinh 7.12). H巽nh 7.12. c叩炭u tru誰c b叩c1 cu鱈a ph叩n t脱鱈 ARN 2.2. C叩炭 u tru誰c b叩短 c 2 ARN ch竪 co誰 m辰端t s奪端i polynucleotid, ch竪 co誰 nh脱樽ng 但oa短n g叩旦n nhau m奪誰i li達n k達炭t v奪誰i nhau theo li達n k達炭t hydro va狸 theo quy lu叩短t b辰淡 sung: A - U b奪鱈i 2 li達n k達炭t hydro. G - C b奪鱈i 3 li達n k達炭t hydro. Ca誰 bi達短t cu樽ng co誰 ARN g辰旦m 2 s奪端i polynucleotid xo探n va狸o nhau da短ng m奪鱈 nh脱 reovirus g叩y b達短nh cho loa狸i 但辰端ng v叩短t co誰 vu誰. 2.3. Ca誰c loa短i ARN 143
  • 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 UU U U A G U A UU UUU G C C UG A A G G U A A U U U GGUAG UUA U A G U U U C G UAA C A U A G A A G G UC U U G G A A CC G C G C G A C C A G U CU A U G U U U A U G U A U U A U A A U U U A G A U GGUG G CC UU UC G A U A UU G U U G AG C U U G GA G U UU U U UUC UG C G UG U A A UCC AUU AAAAACA G UA G A UU A AG UU UGU A U U A U U G C G CA A GG U A A U AUUUGU U U U GC U A G G C GA G AUU U G U U U U UAA A U U A C U A G G C G U U G G U C A GA U G U G U U G C U G C G C U U U A U U A G C A U G C C G C U U A A U C G U GU AA G C U AU U G U U G UU U U A G U GA U G UUGUGCU U C GU G G U G C U A G A A C UA G A A U G G G C G U U A UU G U G U A UU A U G A GUC G U G U A U U AU G U CG U G UCU G G A U U A U U UA A U A A G U AG G UA C GU U A G C CGU A U U C U A U U G U G G U G UUA U A G A A U A GC U A UU A G CG A U U A G G CC A A U U A U A U U G U A U UU A A U C G U U AU A UA U U G G C G U A GA A A U C U A CUC G C G AA U G C G A G U U G UA U A G CUG A G C G AA G U A U AU UU G A U U UA U C G U CUA U U A U U G U C G U G CG U G A AU CUGA U A A U U G CU A A G U A G CU A U U A U A U A C U G A AG GU GU UA U U U A A A GACG G U U G U C A U G UUUAG U A G U U U U A G G U U A U CU U C U U A U G C G U AU U G A U G U U A U C GG A C G G U G U U G U G U G UAG U A A U AA G G A U A AGU A U A UG U U G C G GG U G U U G U A G GAA U UGA U UG G U A U G AG CA A A U C C A U C UC G G UG C G U G C G A U U G G UU C G U G G A G U U A U G G C U A UU GA U C G U UG U A U UA U U G G G U UC C A C U G U UC G G U U AU G U A U U G G U U G G o U A UC G G A A U CU U U U U G G A C U A U G A U A C UU G A G A A 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 +
  • 23. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic Ca誰c giai 但oa短n cu鱈a s脱短 ta誰i ba鱈n: S奪 但辰旦 ta誰i ba鱈n d脱短a va狸o s脱短 th脱短c nghi達短m tr達n E.Coli nh脱 sau: - Nh叩短n di達短n 但i達淡m b探t 但叩旦u: nhi達旦u protein tham gia s脱短 nh叩短n di達短n 但i達淡m b探t 但叩旦u giu誰p cho primase t辰淡ng h奪端p ARN m辰旦i. - M奪鱈 vo狸ng xo探n ke誰p ADN 但脱奪端c xu誰c ta誰c b奪鱈i enzym helicase, n奪i hai s奪端i 但脱奪端c ta誰ch ra go端i la狸 cha短c ba ta誰i ba鱈n. - Ta短o ARN m辰旦i, primase g探n va狸o 但i達淡m b探t 但叩旦u xu誰c ta誰c t辰淡ng h奪端p ARN m辰旦i b辰淡 sung v奪誰i ADN. - Ta短o ADN. * M辰端t s奪端i 但脱奪端c t辰淡ng h奪端p li達n tu短c theo h脱奪誰ng cu鱈a cha短c ba ta誰i ba鱈n (5 - 3) xu誰c ta誰c b奪鱈i enzym polymerase III. * S奪端i kia t辰淡ng h奪端p kh辰ng li達n tu短c, s奪端i na狸y g辰旦m nh脱樽ng 但oa短n khoa鱈ng 1000 - 2000 nucleotid go端i la狸 但oa短n okazaki, m辰湛i 但oa短n b探t 但叩旦u b嘆ng m辰端t m叩湛u ARN m辰旦i r辰旦i t辰淡ng h奪端p ke誰o da狸i b奪鱈i ADN polymerase III, sau 但o誰 ARN m辰旦i 但脱奪端c ta誰ch ra b奪鱈i enzym exonuclease, polynurase I xu誰c ta誰c t辰淡ng h奪端p 但oa短n ADN thi達炭u, ca誰c 但oa短n Okazaki la短i 但脱奪端c n辰炭i li達旦n nh奪狸 xu誰c ta誰c cu鱈a ADN ligase (H巽nh 7.28). H巽nh 7.28a. T辰淡ng h奪端p ADN 156
  • 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 158
  • 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
  • 27. Ho誰a ho端c va狸 chuy達淡n hoa誰 acid nucleic 但辰旦ng th奪狸i v奪誰i s脱短 tng n辰旦ng 但辰端 acid uric trong ma誰u va狸 n脱奪誰c ti達淡u, co誰 s脱短 l探ng 但o端ng tinh th達淡 urat 奪鱈 su短n, bao g叩n, tu誰i nha狸y cu鱈a ca誰c kh奪誰p, 但辰i khi co狸n co誰 trong th叩短n, da va狸 c奪. Xung quanh urat k達炭t tinh la狸 t辰淡 ch脱誰c vi達m h巽nh ca誰c ha短t goutte bao quanh m辰 ch達炭t, th脱奪狸ng g短p 奪鱈 ca誰c kh奪誰p g叩y vi達m kh奪誰p ma樽n t棚nh. 160