NUCLEOPROTEIN &

ACID NUCLEIC

ThS. Nguyen Th Minh Thuan

AI CNG
Nucleoprotein

Nucleoprotein= protein + nhom ngoai (acid nucleic)

Tat ca moi te bao song eu cha nucleoprotein

Protein n gia n (histon hoa protamin) c

Acid nucleic (Polynucleotic)

Ribonuclease Desoxyribonuclease Mononucleotid Mononucleotidase

cung hoan toan gom nucleoprotein.

Chat nhiem sac (cromatin)

Nucleosid

Acid phosphoric

Base (Purin hoa Pyrimidin) c

ose (g) n (Ribose hoa Desoxyribose) c

ACID NUCLEIC

2 loai acid nucleic (theo thanh phan cau tao cua ose )

- Acid ribonucleic (ARN) neu ose la ribose va

- Acid desoxyribonucleic (ADN) neu ose la desoxyribose

ADN chu yeu nhan, ARN nhieu trong te bao chat. Vai tro sinh hoc: ADN mang tnh chat di truyen. ARN tham gia vao tong hp

protein.

Trong te bao, dang ket hp vi protein

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Thanh phan cau tao cua acid nucleic

Acid nucleic la chat trung hp t nhng nucleotid, c goi la polynucleotid.

Cac nucleotid noi vi nhau bang lien ket phosphodieste: nhom -OH C3 va C5 lien ket vi nhau thong qua phan t H3PO4

Nucleotid co the thuy phan thanh 3 cau t: base d vong co nit, pentose va acid phosphoric.
Nucleotid la nhng chat gi vai tro quan trong trong s bien dng trung gian, th du nh tch tr nang lng (ATP) hay la nhng coenzym(NAD+, NADP+, FAD, Coenzym A)
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Pentose

Trong ARN ose la -D-Ribose Trong ADN ose la -2-desoxy D-Ribose Cac nguyen t C xp lien tc nen c anh s th t co du phy tren u: C1', C2' cho n C5'.

- D_Ribose

- 2 _deoxy

D_Ribose
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Pentose

Cac phan t ng nay co ba v tr quan trng cha nhom -OH t do: -Nhom -OH C1' tao lien kt N-glycosid vi goc -NH ca cac base e to thanh cac nucleosid -Nhom -OH C5' tao lien kt ester vi nhom phosphat e to thanh cac nucleotid - Nhom -OH C3' tao lien kt phosphodieste vi nhom phosphat ca mt nucleotid khac e to chui polynucleotid. Tnh phan cc (polarity) trong gc ng c th hin hai v tr C5' va C3 quyt nh tnh phan cc ca cac chuoi polynucleotid

Base co nit

Thuoc loai hp chat d vong pyrimidin va purin, trong o mot hay nhieu nguyen t hydrogen c thay the bi nhng goc hydroxyl, amin hay metyl Purin va pyrimidin cha cac nguyen t N nm xen ke vi cac nguyen t C anh s cac v tr khong them du phy tren u nh trong trng hp ca ng pentose
6 1 7 4 3 8 2

N N
3

N NH
9

N N
1

5 6

Purin

Pyrimidin
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Base co nit co nhan pyrimidin

Co 3 loai: cytosin, uracil va thymin

Trong ARN co cytosin va uracil Trong ADN co cytosin va thymin

NH 2

NHO 2

H N N
O O NH NH

HHNN N

OONH 2 CH 3

HN HN
O

O CH 3

NH

OOONH NH NH

O NH NH

osin

mino pyrimidin

Uracyl Cytosin 2_oxy ,4_amino pyrimidin 2 4 _dioxy

Thymin Uracyl Cytosin

2_oxy 4_amino pyrimidin 2,5_metyl uracyl 4 _dioxy pyrimidin

Thymin Uracyl 5_metyl uracyl 2,4 _dioxy pyrimidin

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Base co nit co nhan purin

Hai base trong ARN va ADN la: Adenin va Guanin

NH 2

N N

N NH
H 2N

N N Guanin

N NH

Adenin
6_amino purin

2 _amino 6_oxy purin

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Acid Phosphoric

La acid v c co cha phospho (P), mt nguyen t ong vai tro quan trng trong trao i cht va nng lng ca t bao Cha ba nhom -OH nen co th hnh thanh lien kt este vi cac gc ng ti v tr C5' va C3' to nen cac nucleotid va chui polynucleotid -Trong cac nucleotid ca DNA va RNA: nhom phosphat lien kt vi cac nucleosid ti C5' -Trong trng hp phan t iu hoa AMP vong (cyclic AMP = cAMP): nhom phosphat to lien kt este vi hai nhom -OH C5' va C3' trong cung mt nucleotid

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NUCLEOSID

Gom 2 thanh phan: base purin hay pyrimidin va pentose.

Lien ket bang noi N9 cua base purin (hoac N1 cua base pyrimidin) vi C1 cua pentose, voi s loai ra 1 phan t nc. Lien ket osidic di dang (-N-glycosid) Pentose di dang furanose
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NUCLEOSID

Nucleosid co nhan pyrimidin co ten tan cung la idin. Nucleosid co nhan purin co ten tan cung la osin.
NH 2 O

N
1

N N
H 2N HO

N N O N
9

O HO

OH OH

OH OH

Cytidin

Guanosin
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NUCLEOTID

Mononucleotid la n v c s cua acid nucleic Mononucleotid c tao thanh khi chc alcol cua pentose c este hoa bi

acid phosphoric (H3PO4) este phosphat ca cac nucleosid

Mononucleotid thuy giai bi H+ yeu cho Base + Pentose Phosphat

Mononucleotid thuy giai bi OH- yeu cho Base Pentose (Nucleosid) + Phosphat

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NUCLEOTID

3 v tr co the phosphoryl hoa cua ribonucleosid (OH C2, C3, C5). Desoxyribonucleosid ch co the phosphoryl hoa C3 va C5.

Mi nucleotid gm ba thanh phn:

-gc ng pentose ni vi mt base nit ti C1 bng mt lien kt -glycosid -gc ng pentose ni vi nhom phosphat ti C5 bng mt lien kt

phosphomonoeste

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NUCLEOTID

Nucleotid vong khi H3PO4 este hoa 2 nhom OH cua pentose cung 1 luc (OH 2 va 3 hoac 3 va
5)
O _

NH 2

NH 2

N N
O P O _ O

N N
O

N N
CH 2 _

N
9

N O

P O O OH

Quan trong nhat la AMP vong

(Adenosin 3'-5'-cyclic monophosphat )

ong vai tro ieu hoa, tai nap tn hieu

OH OH

AMP

cAMP

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NUCLEOTID

Nhieu to chc ong vat con co cac nucleosid di va triphosphat (C5)

Nhiu nhom phosphat co th ni nhau thanh mt day bng cac lien kt phosphoanhydrid Nhng nucleosid di va triphosphat tham gia phan quan trong trong chuyen

hoa cac chat c the va qua trnh trao oi nang lng.

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NUCLEOTID
NH 2

N N
_ O HO P O O O P O _ O _ O O P O CH 2

N
Adenin
9

N O
Ribose OH OH

Adenosin 5 '_monophosphat Adenosin 5 '_diphosphat Adenosin 5'_triphosphat

(AMP)

(ADP)

(ATP)

Cu truc chi tit ca cac nucleotid adenosin ba trng thai mono-, di- va 17 triphosphat

Chc nang sinh hoc cua Nucleotid

Nucleotid tham gia vao nhieu phan ng hay cac qua trnh sinh hoc nh tong hp protein, tong hp acid nucleic, c che ieu hoa va truyen thong tin. Nhng chc nang sinh hoc khac nhau cua nucleotid nh: la chat d tr va van chuyen nang lng, tham gia cau tao coenzym, la chat truyen thong tin th hai. Cac nucleotid ong vai tro sinh hoc trong c the nh: ATP, GTP, UDP, CTP, AMPc, GMPc, adenosin 3-phosphat-5-phosphosulphat, S-adenosylmethionin, cac coenzym la dan chat cua adenosin monophosphat

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Chc nang sinh hoc cua Nucleotid

ATP: ong vai tro d tr va van chuyen nang lng.

ATP la nguon nang lng chu yeu cho phan ln cac phan ng trong te bao. S thuy phan ATP va cac nucleosid triphosphat khac giai phong nang lng nh cau tao hoa hoc cua triphosphat

Thuy phan lien ket este (gia ribose va phosphat) giai phong 14 kJ/mol Thuy phan lien ket anhydrid (gia cac phosphat) giai phong 30 kJ/mol
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Chc nang sinh hoc cua Nucleotid

GTP: la nguon nang lng cho qua trnh tong hp protein.

UDP, UTP: Cac hp chat giau nang lng, co vai tro quan trong trong chuyen hoa glucid. ac biet la trong cac phan ng epime hoa, trong tong hp glycogen, tong hp galactose, tong hp oligosaccarid cua glycoprotein va proteoglycan.
UDP-glucuronic tham gia trong phan ng lien hp glucuronic cua bilirubin va mot so thuoc nh aspirin.

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Chc nang sinh hoc cua Nucleotid

CTP: Tham gia trong tong hp phosphoglycerid, sphingomyelin, sphingosin.

AMPc, GMPc
AMPc la chat truyen thong tin th hai, c tong hp t ATP va ch co te bao ong vat va vi khuan

Trong qua trnh gian c trn, GMPc la chat truyen thong tin th hai ap ng lai NO.

S-adenosylmethionin
La chat van chuyen goc methyl trong phan ng methyl hoa (v du trong chuyen hoa lipid).
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Chc nang sinh hoc cua Nucleotid

CTP: Tham gia trong tong hp phosphoglycerid, sphingomyelin, sphingosin. AMPc, GMPc
AMPc la chat truyen thong tin th hai, c tong hp t ATP va ch co te bao ong vat va vi khuan Trong qua trnh gian c trn, GMPc la chat truyen thong tin th hai ap ng lai NO.

S-adenosylmethionin
La chat van chuyen goc methyl trong phan ng methyl hoa (v du trong chuyen hoa lipid).
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Chc nang sinh hoc cua Nucleotid

Adenosin 3-phosphat-5phosphosulphat
La chat chuyen goc sulfat trong tong hp proteoglycan, trong phan ng lien

P O Adenin Ribose P O O
2

SO 3

hp sulfat vi thuoc.

5' Adenosin '_phosphat_phosphosulfat 3

Coenzym
Nhieu coenzym la dan chat cua adenosin monophosphat c trnh bay trong bang sau
N
O R O P O _ O

NH 2

N
9

Adenin

N
CH 2 n

N O

R" O

OR'
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Chc nang sinh hoc cua Nucleotid

Coenzym 3,5-cAMP NAD NADP FAD CoASH R Dan chat cua vitamin B Dan chat cua vitamin B Dan chat cua vitamin B Dan chat cua vitamin B R H H PO32H H R PO32H H H PO32n 1 2 2 2 2

NH 2

N
O R O P O _ O

N
9

Adenin

N
CH 2 n

N O

R" O

OR'

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Chc nang sinh hoc cua Nucleotid

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Chc nang sinh hoc cua Nucleotid

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Chc nang sinh hoc cua Nucleotid

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Cac chat tong hp co cau tao tng t nucleotid c dung trong hoa tr lieu

Cac chat tong hp 'tng t giong nhan purin, nhan pyrimidin, nucleosid, nucleotid bang cach thay oi tren nhan d vong hay tren phan ng c dung rat nhieu trong ieu tr y hoc. Tac dung chu yeu cua no la c che cac enzym trong qua trnh tong hp acid nucleic hay tham gia trc tiep vao qua trnh tong hp nucleic va lam pha v cau truc DNA. Trong ieu tr ung th, cac chat tng t tham gia trc tiep vao qua trnh tong hp DNA khi te bao phan chia nh: 5-fluoro hay 5-iodouracil, 3-deoxyuridin, 6-

thioguanin, 6-mercaptopurin, 5- hay 6-azauridin, 5- hay 6-azacytidin, 8-azaguanin ..Azathioprin ma chat chuyen hoa cua no la 6-mercaptopurin c dung nh thuoc chong thai ghep trong ghep c quan.
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Cac chat tong hp co cau tao tng t nucleotid c dung trong hoa tr lieu
O O

HN
O HO

I N
O

HN
O HO

N O

N
O

HN
O

F NH

N
H 2N

N N N NH

OH OH

OH OH
6_Azauridin

_deoxyuridin 5 _Iodo_ 2'

SH

5_Fluorouracil

8_Azaguanin

SH

OH

N N

N NH
H 2N

N N

N NH

N N

N N N

6_Mercaptopurin

6_Thioguanin

Alloburinol
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CAU TRUC CUA ACID NUCLEIC

Cau truc cua ADN

ADN tap trung chu yeu cac nhan te bao, cau tao nen cac gen. S hieu biet ay u ve cau truc va tnh chat cua no se giup hieu ro c che cua s di truyen.

Ve mat cau tao hoa hoc, acid nucleic gom rat nhieu mononucleotid trung hp vi nhau tao thanh chuoi polynucleotid.
ADN co phan t lng t 4.000.000 ti 8x106 va gom khoang t 12.000 en 25.000 mononucleotid khac nhau.

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Cau truc cua ADN

Lien ket gia cac mononucleotid
NH 2 R1 P O O

trong phan t ADN la lien ket 3-5 HO phosphodiester. Mot n v ADN gom 2 chuoi polynucleotid xoan chung quanh mot truc chung theo 2 hng ngc nhau. Chuoi polynucleotid co tnh phan cc: au 5 thng co goc phosphat t do, au 3 thng co OH t do

N N
CH 2

N
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Adenin

N O
O H O

HN N
CH 2

N
Guanin

HO

P O H N 2 O

N O
O H O CH 3 Thymin

HN
O CH 2

HO

P O O

N O

H O HO P O R2

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Cau truc cua ADN

Hai chuoi polynucleotid noi vi nhau bi nhng lien ket hydro tao gia 2
base theo nguyen tac: A bo sung cho T, G bo sung cho C
H N H O

N
R1 HO P O O CH 2

N N
H N H O

HN N O
O

CH 3

N O

O CH 2 O P OH

H O HO P O O CH 2

N N O
O H N H

HN N

N N

O
CH 2 O HO P O R2

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Cau truc cua ADN

Ty le cac base purin va pyrimidin (Chargaff va Bielozecki) - base purin = base pyrimidin - Adenin = Thymin A+G=C+T

- Guanin = Cytosin
- Guanin + Cytosin = Adenin + Thymin

A+T > G+C AND loai AT. Neu A+T / G+C > 1 thc vat
G+C > A+T AND loai GC. Neu A+T / G+C < 1 vi khuan
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Cau truc cua ADN

Chuoi xoan kep cua ADN

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Cau truc cua ADN

Cau truc cac nucleotid ien hnh

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Cau truc cua ARN

ARN co cau tao tng t ADN vi 3 iem khac biet: -Phan t ARN la chuoi n -ng pentose la Ribose -Base Uracil thay the Thymin
Cuon
C C G A A A U U C G U U U U C G G G C U U U G G C C A A C A G C

Tay

5'

36 ' 3

Cau truc cua ARN

ARN co phan t lng nho hn ADN khoang 18.000 - 35.000, co khi ti 1.500.000 - 2.000.000 gom 4.000 - 6.000 mononucleotid Phan t ARN gom mot si polynucleotid trong o co nhng oan cua si gan nhau co the lien ket vi nhau theo nh luat oi base bo sung: A - U va G - C e tao ra cau truc xoan. Moi te bao song, ong vat, thc vat cung nh vi khuan eu cha 3 loai ARN: ARN ribosom (ARNr); ARN van chuyen (ARNt) va ARN thong tin

(ARNm).

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Cau truc cua ARN

ARNt (transfer RNA) ARNt co t 74-95 nucleotid chiem khoang 10% tong so ARN.
Van chuyen cac acid amin hoat hoa en ribosom e tong hp protein t cac mARN tng ng, do trnh t anticodon va OH 3 tan cua bo ba CCA-OH khong tham gia xoan kep thc hien Co t nhat 20 loai ARNt cho 20 lai acid amin. Cau tao cua cac ARNt khac nhau trnh t oan polynucleotid nhng tat ca ARNt co cau tao chung la cau truc bac I (trnh t oan polynucleotid) cho phep no gap lai c va t ket hp base noi phan t tao ra mot cau truc bac II co dang la che 3. Tat ca ARNt eu co 4 nhanh chnh.

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Nhanh tiep nhan co au tan

cung ket thuc bang nhom CpCpAOH. Nhom COOH cua acid amin gan vao nhom 3-OH cua Adenin.
5'
G G G C G U U G U G C G G C G C

Nhanh oi ma co mang 3
nucleotid oi ma.

Nhanh D
G A C G G A

3' A C Nhanh nhan acid amin C A C C U G C Nhanh T U C U U A A G G C C G C U C C G G

C G A D A G G G G G

Nhanh D, T C va nhanh phu

giup phan biet cac ARNt.

C U C C C U U G

Nhanh oi ma

ARNt

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Cau truc cua ARN

RNAr (Ribosomal RNA)

Chiem 80% tong so ARN, co vai tro nh nha may tong hp protein.
ARNr la mot nucleoprotein co hai tieu n v, tieu n v ln la 60s va tieu n v nho 40s. Tieu n v 60s co cau tao gom ARNr 5S, ARNr 5.8S, ARNr 28S va khoang 50 chuoi polypeptid. Tieu n v nho cau tao gom ARNr 18S va gan 30 chuoi polypeptid

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Cau truc cua ARN

ARNm (Messenger RNA)

La ARN thong tin vi vai tro chuyen thong tin t gen va lam mau cho qua trnh tong hp protein.
La loai ARN a dang nhat ve kch thc va tnh ben. Chiem khoang 5% tong so ARN. ARNm te bao co nhan co mot so ac iem hoa hoc rieng. au 5 cua ARNm co mang mot phan t 7-metylguanosin triphosphat va c goi la mang mu. mu la ni nhan biet ARNm cua bo phan giai ma, ngoai ra mu con anh hng en tnh ben vng cua ARNm do bao ve ARNm khoi s tan cong cua 5-exonuclease.
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Bo may tong hp protein bat au t au 5 hay au co mu.

Nhom hydroxy cua au 3 con lai gan oan polyme cua adenin vi chieu dai 20-250 nucleotid. Chc nang cua uoi poly A nay cha c ro, nhng dng nh no bao ve cho ARNm khoi s tan cong cua 3-exonuclease. Co mot so ARNm khong co uoi polyA. V uoi polyA co the cap oi vi oan oligodeoxythymidin nen oan polyme nay c gan vao mot c chat nh cellulose dung e tach ARNm ra khoi cac ARN khac.

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