1 Metabolism of nucleic acids

2 Nucleoprotein in foods proteinnucleotides Ribonuclease(deoxyribonuclease) nucleotidases nucleosidases Bases pentoses phosphates catabolism reused

3 1. biosynthesis of purine nucleotides (1) The sources of the nitrogen and carbon atoms of the purine ring

4 N from ASP C 2, C 8 ---fromFH 4 N 3, N 9 ---from Gln C 6 ---from CO 2 N 7, C 4, C 5 ---from Gly

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6 (2) The sources of the phosphopentose * Pentose phosphate pathway

7 PRPP synthetase

8 (3) Two pathway of the synthesis a. De novo synthesis * characteristics * process

9 PRPP Gln(N9) NH 2 -1-R5P Gly(C4,5N7) N 5 N 10 =CH-FH (C8) Gln(N3) CO 2 (N6) ASP(N1) N 5 N 10 -CHO-FH (C2) IMP

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11 # synthesis of IMP Key enzyme –PRPP glutamyl aminophospho ribosyl transferase # IMP convert to AMP,GMP

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13 b. salvage synthesis * concept * process

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16 Enzymes # on the level of bases adenine phosphoribosyl transferase (APRT) hypoxanthine guanine phosphoribosyl transferase (HGPRT)

17 # on the level of nucleoside Adenosine kinase Defect of HGPRT----- Lesch-Nyhan syndrome (a bizarre syndrome of self – mutilation)

18 * characteristics c. Regulation of purine nucleotide biosynthesis

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20 d. Antagonists of purine nucleotide biosynthesis e. Summarize

21 2. biosynthesis of pyrimidine nucleotides (1) The sources of the nitrogen and carbon atoms of the pyrimidine ring

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23 N from ASP C 4,5,6 ---from ASP C from CO 2 carbomyl N from Gln phosphate

24 (2) Two pathway of the synthesis a. De novo synthesis * characteristics * process

25 # synthesis of carbomyl phosphate * enzyme carbomyl phosphate synthetase II

26 carbomyl phosphate synthetase I synthetase II Site mitochondrion cytosol Catalytic 2ATP+NH 3 +HCO 3 - 2ATP+Gln+HCO 3 - reaction NH 2 -CO-O-P NH 2 -CO-O-P Product synthesis of urea synthesis of pyrimidine

27 # synthesis of UMP *Key enzyme---asparate transcarbamoylase *Multifunctional enzymes

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31 b. Regulation of pyrimidine nucleotide biosynthesis c. salvage synthesis * concept * process

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33 d. Summarize

34 3. Formation of deoxyribonucleotides (1) summary (2) enzyme

35 * Ribonucleotide reductase (RR) a.the characteristics of RR b. catalytic reaction

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37 c.regulation of RR activity (3) the synthesis of dTMP

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40 (4) Antagonists of deoxy- nucleotide biosynthesis

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42 4. Catabolism of purine nucleotides (1) Process (2) final product---uric acid (3) gout

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46 5. Catabolism of pyrimidine Nucleotides * final products

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49 ● 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 ）。

50 ● 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。