DNA and RNA are nucleic acids that store and help express genetic information. DNA is composed of nucleotides containing deoxyribose, phosphates, and one of four nitrogenous bases (adenine, guanine, cytosine, thymine). RNA is similar but contains ribose and uracil instead of thymine. The genetic code is stored in DNA as base pair sequences in chromosomes. During cell division, DNA replicates and genes direct protein production through transcription of DNA to mRNA and translation of mRNA to proteins.
DNA and RNA are nucleic acids that store and help express genetic information. DNA is composed of nucleotides containing deoxyribose, phosphates, and one of four nitrogenous bases (adenine, guanine, cytosine, thymine). RNA is similar but contains ribose and uracil instead of thymine. The genetic code is stored in DNA as base pair sequences in chromosomes. During cell division, DNA replicates and genes direct protein production through transcription of DNA to mRNA and translation of mRNA to proteins.
1. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Ch æ å n g 7
ACID NUCLEIC
Muûc tiãu:
1. Viãút âæåüc cäng thæïc thaình pháön cáúu taûo cuía
acid desoxyribonucleic (ADN) vaì cuía acid ribonucleic (ARN).
2. Mä taí âæåüc âàûc âiãøm cáúu truïc cuía ADN vaì ARN.
3. Kãø âæåüc caïc saín pháøm thoaïi hoïa trung gian vaì
caïc saín pháøm thoaïi hoïa cuäúi cuìng cuía acid nucleic.
4. Mä taí âæåüc quaï trçnh täøng håüp ADN, ARN.
5. Nãu ra âæåüc yï nghéa lám saìng cuía sæû chuyãøn
hoïa acid nucleic.
Pháö n 1.
HOÏA HOÜC ACID NUCLEIC
I. ÂAÛI CÆÅNG.
Acid nucleic (AN) laì håüp cháút quan troüng báûc nháút
trong sæû di truyãön vaì täøng håüp protein. Táút caí cå thãø
säúng âãöu chæïa AN dæåïi daûng tæû do hoàûc dæåïi daûng
kãút håüp våïi protein taûo nucleoprotein
AN trong cå thãø dæåïi 2 daûng chênh:
- Acid ribonucleic (ARN).
- Acid deoxyribonucleic (ADN).
II. THAÌNH PHÁÖ N CÁÚU TAÛO ACID NUCLEIC (AN):
Thaình pháön cáúu taûo AN gäöm: H 3 PO4 , pentose, base nitå.
1. Cáúu taûo pent o s e
OH
CH2
O
OH
OH
OH
CH2
OH
OH
OH
O
H
β- D ribose
β-2 deoxy D ribose
Hçnh 7.1. Ribose vaì Deoxyribose
2. Cáúu taûo cuía bas e coï nitå
Base coï nitå âæåüc dáùn xuáút tæì 2 nhán dë voìng laì purin
vaì pyrimidin.
2.1. Bas e pyri m i d i n
Base coï nhán pyrimidin gäöm cytosin, uracil vaì thymin (Hçnh
7.2)
134
2. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
1N
H
6C
HC
2
5
CH
CH
4
N
3
H
4C
3N
hoàû
c
HC
2
5
CH
CH
6
N
1
Nhán pyrimidin
Cytosin (kyï hiãûu C): 2 hydroxy 6 amino pyrimidin:
NH 2
NH 2
N
HO
N
O
N
N
H
daûng enol (lactim)
daûng ceton (lactam)
Uracil (U): 2,6 dihydroxy pyrimidin:
OH
O
H
N
HO
N
O
N
N
H
daûng enol
Thymin (T): 5 methyl uracil.
daûng ceton
OH
N
HO
O
CH 3
H
O
N
CH 3
N
N
H
daûng enol
daûng ceton
Hçnh 7.2. Base pyrimidin: cytosin, uracil vaì thymin
2.2. Bas e purin
Base coï nhán purin gäöm adenin vaì guanin (Hçnh 7.3)
Ngoaìi thaình pháön trãn, ARN, ADN coìn chæïa thãm
mäüt säú base nitå khaïc:
ADN vi khuáøn coï N.6 metyl adenin, 5 hydroxymetyl cytosin.
ADN thæûc váût (máöm luïa), âäüng váût (tuyãún æïc) coï
5 metyl cytosin.
ARNr vaì ARNt coìn chæïa base purin vaì pyrimidin metyl
hoïa. ARNt coìn chæïa pseudouridin; hypoxanthin; 1 metyl
hypoxanthin; 5,6 dihydrouracil.
135
3. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
6
1N
5
2
N
3
4
NH 2
N7
N
8
N
9
N
N
Nhán 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
Daûng enol
Daûng ceton
Hçnh 7.3. Base purin: adenin vaì guanin
III. NUCLEOSID VAÌ NUCLEOTID
1. Nucle o s i d
Nucleosid laì saín pháøm thuíy phán khäng hoaìn toaìn
cuía AN gäöm base nitå liãn kãút våïi pentose bàòng liãn kãút
glucosid. Liãn kãút naìy âæåüc thæûc hiãûn giæîa C1’ cuía
pentose vaì N3 cuaí base pyrimidin hoàûc giæîa C1’ cuía
pentose vaì N9 cuaí base purin. (Hçnh 7.4)
Caïch go üi tãn:
Tuìy theo thaình pháön cuía base nitå vaì cuía pentose caïch
goüi tãn nhæ sau:
Tãn chung:
Ribonucleosid
Deoxyribosenucleosid
(Pentose laì Ribose)
(Deoxyribose)
Tãn riãng cuía caïc nucleosid theo base nitå:
Adenin
Adenosin
Deoxyadenosin.
Guanin
Guanosin
Deoxyguanosin.
Uracil
Uridin
Deoxyuridin
(êt)
Cytosin
Thymin
Cytidin
Ribothymidin
136
Deoxycytidin.
(êt)
4. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Deoxythymidin.
NH2
N
N
N
N
O
Adenin
CH2OH
Ribose
OH OH
Adenosin
Hçnh 7.4. Nucleosid coï base adenin
2. Nucle oti d (nucl e o s i d pho s p h a t )
Caïc nucleosid thæåìng khäng åí traûng thaïi tæû do maì
kãút håüp våïi H 3 PO4 taûo thaình nucleotid, trong âoï pentose
liãn kãút våïi H 3 PO4 båíi liãn kãút este åí caïc vë trê 2’, 3’, 5’.
Nucleosid
monophosphat
coìn
âæåüc
goüi
laì
mononucleotid, âån vë cáúu taûo cuía acid nucleic, gäöm coï
base nitå, pentose vaì acid phosphoric (Hçnh 7.5.)
NH2
N
O
N
N
N
O
Adenin
CH2O
P
OH
OH
Ribose
OH OH
Adenosin-5'-monophosphat (AMP)
Hçnh 7.5. Nucleosid monophosphat coï base
adenin
Caïch goü i tãn:
Nucleotid coï thaình pháön laì ribose, âæåüc goüi laì ribonucleotid.
Nucleotid coï thaình pháön laì deoxyribose, âæåüc goüi laì
deoxyribonucleotid.
Goüi theo base N: Ribosid 5’ monophosphat
Deoxyribosid 5’
monophosphat
Adenin:
Adenosin 5’ monophosphat
137
5. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Deoxyadenosin5’monophosphat (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 (êt)
monophosphat
Deoxythymidin 5’
(dTMP)
Caïc nucleotid coï thãø kãút håüp våïi 2 hoàûc 3 phán tæí H 3 PO4
âãø taûo thaình nucleosid diphosphat vaì nucleosid triphosphat giæî
vai troì quan troüng trong cå thãø.
3. Caïc nucle o ti d tæ û do qua n troü n g
3.1. Dáù n xuáú t ad e n i n
-Adenosin diphosphat vaì triphosphat (ADP, ATP)
7.6)
(Hçnh
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)
Hçnh 7.6. Cáúu taûo cuía AMP, ADP vaì ATP
- Vai troì ADP vaì ATP:
+ Tham gia phaín æïng phosphoryl hoïa.
+
ATP
laì
nguäön
phosphat giaìu nàng læåüng, dæû træî vaì cung cáúp nàng
læåüng cho caïc phaín æïng.
+ Hoaût hoïa caïc cháút
+ Adenosin monophosphat voìng (5’, 3’ adenosin
monophosphat = AMPv ).
138
6. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
AMP voìng âæåüc hçnh thaình tæì ATP nhåì enzym adenyl
cyclase xuïc taïc, coï vai troì nhæ mäüt cháút thäng tin thæï hai
maì hormon laì cháút thäng tin thæï nháút, tham gia vaìo sæû
hoaût âäüng 1 säú hormon, tham gia täøng håüp hormon (Hçnh
7.7).
- S-Adenosin methionin:
cung cáúp nhoïm metyl cho caïc quaï trçnh (Hçnh 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 voì g
(AMPv)
ATP
Hçnh 7.7. Phaín æïng taûo thaình AMPv
NH3
N
COOH
CH
CH2
CH2
NH2
N
N
CH2
CH2
S
O
N
+
OH OH
S_Ade ylmethion
nos
in
Hçnh 7.8. S-Adenosinmethionin
3.2. Dáùn xuáú t gua ni n : G uanosin di vaì triphosphat
(GDP, GTP) coï vai troì trong täøng håüp protein
3.3. Dáù n xuáú t uracil: Uridin di vaì triphosphat (UDP,
UTP) coï vai troì trong chuyãøn hoïa glucid.
3.4. Dáù n xuáú t cyt o s i n : Cytidin di vaì triphosphat (CDP, CTP):
tham gia täøng håüp phospholipid.
IV. ACID NUCLEIC
1. Cáúu truïc cuía ADN
139
7. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
1.1. Cáúu truïc bá û c I
ADN laì polyme cuía nhiãöu deoxyribonucleotid coï chæïa caïc
base nitå laì adenin, guanin, thymin, cytosin, nucleotid naìy näúi våïi
nucleotid kia båíi liãn kãút 3’, 5’ phosphodieste taûo thaình chuäùi
polynucleotid. (Hçnh 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
Hçnh 7.9: Cáúu truïc báûc 1 cuía ADN
Mäüt âoaûn polynucleotid cuía ADN coï thãø biãøu thë ngàõn
goün nhæ hçnh dæåïi âáy. Trong âoï P biãøu thë liãn kãút
phosphodoieste, caïc kyï tæû bàòng base nitå, âoaûn thàóng âæïng
bàòng âæåìng pentose.
Caïch viãút: pA-C-G-T OH
hay pApCpGpT hay pACGT hay
ACGT våïi âáöu 5’ phosphat vãö phêa tay traïi, âáöu 3’ OH vãö phêa
tay phaíi.
1.2. Cáúu truïc bá û c 2
- Mäùi phán tæí ADN gäöm 2 chuäùi polynucleotid xoàõn theo
140
11. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Trong caïc sinh váût âån baìo vaì âa baìo, coï 3 loaûi ARN
chênh: ARN thäng tin (ARNm), ARN váûn huyãøn (ARNt) vaì ARN
ribosom (ARNr).
- ARNm: mang thäng tin di truyãön maì ADN âaî
phiãn maî cho noï ra ribosom âãø täøng håüp protein. Phán tæíí
ARNm laì mäüt såüi polynucleotid daìi, thàóng chæïa 900 12000 nucleotid, pháûn tæí læåüng khoaíng 3x10 5 âãún 4x10 6 .
ÅÍ tãú baìo coï nhán âáöu 5’ coï mang mäüt phán tæí 7methylguanosin triphosphat vaì âæåüc goüi laì “muî”. Âáöu 3’
coï gàõn nhæîng nucleotid adenylat goüi laì “âuäi poly A” coï
tæì 20 - 250nucleotid (Hçnh 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
Hçnh 7.13. Phán tæí 7-methylguanosin triphosphat
- ARN t: váûn chuyãøn acid amin âãún ribosom âãø täøng
håüp protein. Cáúu taûo tæì 4 base chênh: A, G, C, U vaì nhiãöu
base hiãúm.. Phán tæí coï chæïa tæì 70 - 90 nucleotid, PTL
khoaíng 23 000 - 30 000.
Coï êt nháút 20 phán tæí ARNt cho 20 loaûi acid amin (coï
khoaíng 56 loaûi ARNt khaïc nhau trong mäüt tãú baìo)
Phán tæí ARNt gäöm coï 4 nhaïnh chênh vaì mäüt nhaïnh
phuû vaì coï hçnh dang nhæ mäüt laï cheí ba:
+ Nhaïnh tiãúp nháûn acid amin: kãút thuïc båíi
bäü ba CCA (chiãöu 5’- 3’)
+ Nhaïnh âäúi maî: mang ba nucleotid âäúi maî,
giuïp nháûn ra maî ba nucleotid tæång æïng trãn ARNm laìm
khuän.
+ Nhaïnh D (chæïa nhiãöu Dihydrouridin)
+ Nhaïnh Tψ C coï chæïa Thymidin, Pseudouridin vaì
Cytidin.
144
12. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Ngoaìi ra coìn coï mäüt nhoïm phuû , giuïp ta phán biãût
caïc nhoïm ARNt..
-
Hçnh 7.14. Cáúu truïc phán tæí ARN t
ARN r: liãn kãút våïi protein taûo thaình ribosom laì nåi
täøng håüp protein. ARN r laì mäüt såüi polynucleotid
khäng voìng coï nhiãöu khuïc cuäün, chæïa khoaíng 100 1500 nucleotid (Hçnh 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
Hçnh 7.15. Cáúu taûo ARN r
145
13. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Ribosom cuía loaìi coï vuï coï PTL khoaíng 4,2x10 6 coï
hãû säú làõng 80S,gäöm 2 baïn âån vë: baïn âån vë låïn 60S vaì
baïn âån vë nhoí 40S.
- ARNsn: laì nhæîng ARN âæåüc tçm tháúy åí tãú baìo
nhán tháût, coï nhiãöu trong nhán tãú baìo, tham gia trong cå
chãú càõt boí âoaûn intron trong viãûc hoaìn thiãûn ARNm.
V. SÆÛ KHU TRUÏ AN TRON G TÃÚ BAÌO
- ÅÍ âäüng váût, thæûc váût, vi khuáøn tãú baìo chæïa caí
ARN vaì ADN.
ADN: Chuí yãúu åí trong nhán, ty thãø, haût diãûp luûc.
ARN: Coï trong nhán, haût nhán, ribosom, baìo træång,
ty thãø.
- ÅÍ virus gáy bãûnh khaím thuäúc laï, polio: tãú baìo chè
chæïa ARN.
- ÅÍ thæûc khuáøn thãø adenovirus: tãú baìo chè chæïa
ADN.
.
.
146
14. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
CHUYÃØN
PHÁÖN 2.
NUCLEIC
HOÏA
ACID
I. SÆÛ THOAÏI HOÏA
1. Sæ û thoaïi hoïa chun g
mono n u c l e o t i d
cuía acid nucleic âãú n
ÅÍ caïc mä âäüng váût acid nucleic âæåüc thuíy phán
thaình mononucleotid nhåì enzym nuclease càõt âæït liãn kãút
phosphodieste cuía polynucleotid.
Nuclease gäöm 02 loaûi:
Ribonuclease (RNase) thuíy phán ARN.
Deoxyribonuclease (DNase) thuíy phán ADN.
Mäùi loaûi laûi phán laìm: Exonuclease vaì endonuclease
tuìy theo caïch thuíy phán.
2. Sæ û thoaïi hoïa cuía mon o n u cl e o t i d
Dæåïi taïc duûng cuía nucleotidase, nucleotid bë
thuíy phán thaình nucleosid vaì H 3 PO4 vaì våïi taïc duûng cuía
nucleosidase, nucleosid bë thuíy phán thaình base nitå vaì
pentose (Hçnh 7.16).
Nucleoprot ein
Prot ein t huáön
(Hist on prot am in)
Acid nucleic
(Polynucleot id)
Nuclease
Mononucleot id
Nucleot idase
phosphoric
Nucleosid
Acid
Nucleosidase
Base nit å
Pyrim idin)
Pent ose
( Ribose, Desoxy ribose)
(Purin,
Hçnh 7.16. Caïc saín pháøm cuía sæû t huyí phán acid
nucleic
147
15. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
H 3 PO4 âæåüc sæí duûng cho quaï trçnh phosphoryl hoïa
hoàûc âaìo thaíi dæåïi daûng muäúi phosphat. Pentose thoaïi
hoïa theo âæåìng chuyãøn hoïa cuía glucid. Caïc base nitå thoaïi
hoïa cho saín pháøm laì acid uric, urã...
3. Thoaïi hoïa caïc bas e coï nitå
3.1. Thoaïi hoïa ba s e loaûi purin
Adenin, guanin bë thuíy phán thaình hypoxanthin vaì
xanthin dæåïi taïc duûng cuía adenase, guanase sau âoï oxy
hoïa thaình acid uric dæåïi taïc duûng cuía xanthin oxydase,
ngoaìi ra adenosin cuîng bë khæí amin båíi adenosin
desaminase taûo inosin räöi oxy hoïa cho hypoxanthin vaì cuäúi
cuìng laì acid uric (Så âäö hçnh 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
Hçnh 7.17. Så âäö thoaïi hoaï base purin
3.2. Thoaïi hoïa loaûi ba s e pyri m i d i n
148
16. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Thoaïi hoïa caïc loaûi base pyrimidin xaíy ra chuí yãúu åí
gan vaì chæa biãút roî. Sæû biãún âäøi cuía uracil åí mä âäüng
váût vaì mäüt säú vi khuáøn âæåüc mä taí theo så âäö sau (Så
âäö hçnh 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
Hçnh 7.18. Så âäö thoaïi hoaï base
pyrimidin
II. TÄØN G HÅÜP ACID NUCLEIC
1. Täøn g håü p nucl e ot i d
1.1. Täøn g håü p rib o n u c l e o t i d coï ba s e purin
Ngæåìi ta âaî xaïc âënh âæåüc caïc nguyãn täú trãn nhán
purin coï nguäön gäúc nhæ sau, xem hçnh 7.19.
149
CH3
17. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
CO2
C4,C5,N7: Glycin
Asp
N1
2
Formic
6
N
7
8
5
3 4
N
9
N
Formic
Glutamin
Hçnh 7.19. Så âäö nguyãn liãûu täøng håüp ribonucleotid
coï base purin
Quaï trçnh täøng håüp gäöm 4 giai âoaûn:
Giai âoaûn 1: Bàõt âáöu tæì ribose 5’ (P) âæåüc
phosphoryl hoïa taûo thaình 5’ phosphoribosyl 1 pyrophosphat
(PRPP), sau âoï gàõm amin cuía glutamin räöi kãút håüp våïi
glycin taûo thaình glycimamid ribosyl 5’ (P) våïi sæû tham gia
cuía enzym amidotransferase vaì nàng læåüng do ATP cung
cáúp (Hçnh 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
Hçnh 7.20. Täøng håüp glycinamid ribosyl 5’ phosphat
150
18. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Giai âoaûn 2: Taûo nhán imidazol cuía purin.
Glycimamid ribosyl 5’ âæåüc fomyl hoïa xuïc taïc båíi
enzym transfomylase taûo thaình glycinamidribosyl 5’ , räöi
amin hoïa vaì âoïng voìng taûo thaình aminoimidazol ribosyl 5’
, ATP cung cáúp nàng læåüng (Hçnh 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
Âoïng voìng
N
R
N
++
ATP,Mg
H2N
5'- P
H
R 5'- P
FormylGlycinamidin Ribosyl- P
5'-
Aminoimidazol Ribosyl- P
5'-
Hçnh7.21. Taûo nhán imidazol cuía purin
Giai âoaûn 3: Taûo nhán pyrimidin cuía purin vaì sæû hçnh
thaình IMP: Amidimidazol ribosyl 5’ âæåüc carboxyl hoïa räöi
kãút håüp våïi aspartat taûo thaình 5 amino 4 succino imidazol
ribonucleotid, taïch fumrat räöi fomyl hoïa vaì âoïng voìng taûo
acid inosinic (IMP) (Hçnh 7.22).
Giai âoaûn 4: Chuyãøn acid inosinic thaình acid adenylic
(AMP) vaì acid guanylic (GMP) (Hçnh 7.23).
-
Taûo acid Adenylic:
Acid inosinic ngæng tuû våïi acid aspartic taûo thaình
succino adenin nucleotide, phaín æïng cáön nàng læåüng tæì
sæû phán huíy GTP. Sau âoï taïch acid fumaric âãø taûo thaình
AMP.
151
19. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
-
Taûo acid Guanylic:
Acid inosinic bë xy hoïa åí vj trê C2
cuía purin, sau âoï gàõn
amin âãø taûo thaình GTP. Nàng læåüng âæåüc cung cáúp tæì sæû
phán giaíi 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)
Hçnh 7.22. Taûo nhán pyrimidin cuía purin
Ngoaìi quaï trçnh trãn caïc mononucleotid coìn âæåüc
hçnh thaình tæì caïc base tæû do qua kãút håüp våïi PRPP
(Hçnh 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)
Hçnh 7.23. Täøng håüp mononucleotid tæì caïc base tæû do
152
acid
20. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Caïc phaín æïng cuía giai âoaûn 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)
Hçnh 7.24. Chuyãøn acid inosinic thaình AMP vaì
GMP
1.2. S æ û
täøn g
håü p
pyri m i d i n gä ö m hai giai âoaû n
rib o n u c l e o t i d
coï
ba s e
Giai âoaûn I: Taûo orotat:
Nguyãn liãûu âáöu tiãn laì carbamyl vaì aspartat våïi
sæû xuïc taïc cuía aspartat transcarbamylase seî taûo thaình
carbamyl aspartat, cháút naìy âoïng voìng taûo thaình
dihydroorotat xuïc taïc båíi dihydroorotat räöi oxy hoïa taûo
thaình orotat (Hçnh 7.25).
Giai âoaûn II: Taûo thaình base pyrimidin vaì nucleotid coï
base pyrimidin:
Orotat gàõn våïi ribose 5’ do PRPP cung cáúp våïi sæû
xuïc taïc cuía orotydilic pyrophosphorylase taûo thaình oritidin
5’ räöi bë khæí carboxyl taûo thaình uridin monophosphat
(UMP) xuïc taïc båíi enzym orotidin 5’ decarboxylase (Hçnh
7.26).
153
21. Hoïa hoüc vaì chuyãøn hoaï 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
Hçnh 7.25. Taûo orotat tæì carbamyl vaì 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)
Hçnh 7.26. Taûo nucleotid coï base pyrimidin
154
22. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Uridin monophosphat (UMP) phosphonyl hoïïa 2 láön taûo thaình
uridin triphosphat (UTP), UTP amin hoïa taûo thaình cytidin
triphosphat (CTP).
1.3. Täøn g håü p d e o x y r i b o n u c l e o t i d
Deoxyribonucleotid âæåüc hçnh thaình båíi quaï trçnh khæí oxy
træûc tiãúp åí C2 cuía ribose cuía caïc ribonucleotid:
(ADP, GDP, UDP, CDP)
(dADP, dGDP, dUDP, dCDP)
Ribonucleosid di(P) reductase
(Enzym có vit B1, B2)
ATP
ADP
NDP
dNTP
Nucleosid diphosphat kinase
Hçnh 7.27. Täøng håüp deoxyribonucleotid
Täøng håüp acid deoxythymidylic (dTTP), dTTP khäng coï
ribonucleotid tæång æïng, âæåüc täøng håüp tæì UDP nhæ sau:
Phosphoryl hoïa.
UDP
dUDP
dTTP
2. Täøn g håü p ADN:
dUMP
dTMP
2.1. Sæû taïi baín baío täön cuía ADN
Dæûa trãn cáúu truïc cuía Watson vaì Crick thç mäùi såüi cuía
phán tæí ADN xoàõm keïp âæåüc duìng laìm khuän âãø täøng håüp
mäüt såüi bäø sung theo quy luáût âäi base âãø taûo 2 phán tæí ADN
con, mäüt trong hai såüi naìy laì såüi cuía ADN meû.
Enzym xuïc taïc phaín æïng täøng håüp laì ADN polymerase (I,
II, III). ADN polymerase I xuïc taïc gàõn mononucleotid,
mononucleotid vaìo nhoïm OH åí vë trê 3’ cuía ADN mäöi âãø keïo
daìi theo hæåïng 5’ - 3’.
Ppi
(dNMP) n
+
ADN m äöi, Mg + +
dNTP
(dNMP)
Enzym
dNMP: deoxyribonucleot id 5’m ono
dNTP: deoxyribonucleot id 5’ t ri
155
n + 1
+
24. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
Hçnh 7.28b. Täøng håüp ADN
2.2. Sæû sæía chæîa ADN
Caïc thæång täøn coï thãø xaíy ra trãn ADN:
- Do sai láöm khi keûp âäi trong quaï trçnh taïi baín
- Do yãúu täú ngoaûi lai: nhiãût âäü, tia tæí ngoaûi, tia X
Caïc hãû thäúng sæía chæîa: do haìng loaût enzym, protein:
- Keûp âäi
- Càõt base
- Càõt nucleotid
-Sæía chæîa træûc tiãúp
3. Täøn g håü p ARN
3.1. Quaï trçnh täøng håüp
Enzym täøng håüp ARN laì ARN polymerase:
- ARN poly m e r a s e phu û th u ä ü c ARN (re p lica s e : enzy m
taïi baín). ARN måïi âæåüc täøng håüp dæûa trãn khuän ARN taïc
duûng cuía ARN polymerase, enzym xuïc taïc:
ARN mäöi, 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
Âáy laì sæû nhán âäi ARN cuía virus trong tãú baìo chuí
trong quaï trçnh nhiãùm truìng, ARN (+) cuía virus duìng laìm
khuän âãø täøng håüp såüi ARN (-) bäø sung vaì xoàõn keïp våïi
ARN (+) räöi tæì ARN (-) laûi laìm khuän täøng håüp ARN (+)
157
25. Hoïa hoüc vaì chuyãøn hoaï acid nucleic
cuía virus.
+
+
+
−
+
+
ARN( +)
Xoàõ n keïp
ARN( +)
Hçnh
Sæû nhán âäi cuía virus trong tãú baìo chuí
7.29:
- ARN poly m e r a s e phu û th u ä ü c ADN (tra n s c r i p t a s e :
enzy m sao ch eï p ). Sæû täøng håüp ribonucleotid 5’ monophosphat
trong ARN laì mäüt quaï trçnh sao cheïp båíi vç caïc thäng tin di
truyãön chæïa trong ADN âæåüc sao cheïp sang ARN.
ARN polymerase xuïc taïc täøng håüp ARN cuía tãú baìo (ARN r ,
ARNt , ARNm ) tæì caïc ribonucleotid triphosphat giaíi phoïng
pyrophosphat, phaín æïng cáön ADN laìm khuän, caïc base cuía ARN
täøng håüp bäø sung våïi mäüt trong hai chuäùi cuía ADN vaì phaït
triãøn theo hæåïng 5’ - 3’ (Hçnh 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