1. 1 Metabolism of nucleic acids

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

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

4. 4 N 1 ----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

5. 5

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

7. 7 PRPP synthetase

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

9. 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

10. 10

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

12. 12

13. 13 b. salvage synthesis * concept * process

14. 14

15. 15

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

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

18. 18 * characteristics c. Regulation of purine nucleotide biosynthesis

19. 19

20. 20 d. Antagonists of purine nucleotide biosynthesis e. Summarize

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

22. 22

23. 23 N 1 ---- from ASP C 4,5,6 ---from ASP C 2 --- from CO 2 carbomyl N 3 --- from Gln phosphate

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

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

26. 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. 27 # synthesis of UMP *Key enzyme---asparate transcarbamoylase *Multifunctional enzymes

28. 28

29. 29

30. 30

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

32. 32

33. 33 d. Summarize

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

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

36. 36

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

38. 38

39. 39

40. 40 (4) Antagonists of deoxy- nucleotide biosynthesis

41. 41

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

43. 43

44. 44

45. 45

46. 46 5. Catabolism of pyrimidine Nucleotides * final products

47. 47

48. 48

49. 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. 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。