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Metabolism of nucleic acids

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Nucleoprotein in foods

protein nucleotides

Ribonuclease(deoxyribonuclease)

nucleotidases

nucleosidases

Bases pentoses phosphates

catabolism reused reused

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1. biosynthesis of purine

nucleotides

(1) The sources of the nitrogen and

carbon atoms of the purine ring

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N1----from ASP

C2, C8---fromFH4

N3, N9---from Gln

C6---from CO2

N7 , C4 , C5---from Gly

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(2) The sources of the

phosphopentose

* Pentose phosphate pathway

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PRPP synthetase

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(3) Two pathway of the synthesis

a. De novo synthesis

* characteristics

* process

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PRPP Gln(N9)

NH2-1-R5P

Gly(C4,5N7)

N5N10=CH-FH (C8)

Gln(N3)

CO2(N6)

ASP(N1)

N5N10-CHO-FH (C2)

IMP

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# synthesis of IMP

Key enzyme –PRPP

glutamyl aminophospho

ribosyl transferase

# IMP convert to AMP,GMP

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b. salvage synthesis

* concept

* process

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• Enzymes

# on the level of bases

adenine phosphoribosyl transferase

(APRT)

hypoxanthine guanine phosphoribosyl transferase (HGPRT)

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# on the level of nucleoside

Adenosine kinase

Defect of HGPRT-----

Lesch-Nyhan syndrome

(a bizarre syndrome of self –

mutilation)

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* characteristics

c. Regulation of purine

nucleotide biosynthesis

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d. Antagonists of purine

nucleotide biosynthesis

e. Summarize

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2. biosynthesis of pyrimidine

nucleotides

(1) The sources of the nitrogen and

carbon atoms of the pyrimidine

ring

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N1---- from ASP

C4,5,6---from ASP

C2--- from CO2

carbomyl

N3--- from Gln phosphate

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(2) Two pathway of the synthesis

a. De novo synthesis

* characteristics

* process

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# synthesis of carbomyl

phosphate

* enzyme

carbomyl phosphate

synthetase II

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carbomyl phosphate carbomyl phosphate

synthetase I synthetase II

Site mitochondrion cytosol

Catalytic 2ATP+NH3+HCO3- 2ATP+Gln+HCO3

-

reaction

NH2-CO-O-P NH2-CO-O-P

Product synthesis of urea synthesis of pyrimidine

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# synthesis of UMP

*Key enzyme---asparate transcarbamoylase

*Multifunctional enzymes

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b. Regulation of pyrimidine

nucleotide biosynthesis

c. salvage synthesis

* concept

* process

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d. Summarize

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3. Formation of

deoxyribonucleotides

(1) summary

(2) enzyme

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* Ribonucleotide reductase (RR)

a.the characteristics of RR

b. catalytic reaction

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c.regulation of RR activity

(3) the synthesis of dTMP

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(4) Antagonists of deoxy-

nucleotide biosynthesis

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4. Catabolism of purine

nucleotides

(1) Process

(2) final product---uric acid

(3) gout

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5. Catabolism of pyrimidine Nucleotides

* final products

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● 腺苷脱氨酶（ adenosine deaminase,ADA ）基因缺陷是一种常染色体隐性遗传病

病因：由于基因突变造成酶活性下降或消失，导 致 AMP ， dAMP 和 dATP 蓄积， dATP 是核

糖核苷酸还原酶的别构抑制剂，能减少 dGDP, dCDP 和 dTTP 合成，从而 DNA 合

成受阻。由于正常情况下淋巴细胞中腺苷 酸脱氨酶活性较高，当 ADA 基因缺陷

时，可造成严重损害，导致细胞免疫和体 液免疫反应均下降，甚至死亡，即严重联合免

疫缺陷症（ severe combined immunodeficiency, SCID ）。

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●PNP 基因 (purine nucleoside phosphorylase) 缺陷是一种罕见的常染色体隐性遗传病， 病因是 PNP 不能发挥正常作用，所以患儿体内鸟苷、 脱氧鸟苷、次黄苷及脱氧次黄苷浓度均增加，脱氧鸟 苷转化成 dGTP ，造成 dGTP 堆积，是核糖核苷酸还原 酶的别构抑制剂，导致 dCDP 及 dCTP 下降，最终 DNA 合成不足，影响胸腺细胞增殖，导致 T 细胞免疫缺陷。