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Metabolism of nucleic acids PowerPoint Presentation
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Metabolism of nucleic acids

Metabolism of nucleic acids

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Metabolism of nucleic acids

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  1. Metabolism of nucleic acids

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

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

  4. N1----from ASP C2, C8---fromFH4 N3, N9---from Gln C6---from CO2 N7 , C4 , C5---from Gly

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

  6. PRPP synthetase

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

  8. PRPP Gln(N9) NH2-1-R5P Gly(C4,5N7) N5N10=CH-FH (C8) Gln(N3) CO2(N6) ASP(N1) N5N10-CHO-FH (C2) IMP

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

  10. b. salvage synthesis * concept * process

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

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

  13. * characteristics • Regulation of purine • nucleotide biosynthesis

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

  15. 2. biosynthesis of pyrimidine nucleotides • The sources of the nitrogen and • carbon atoms of the pyrimidine • ring

  16. N1---- from ASP C4,5,6---from ASP C2--- from CO2 carbomyl N3--- from Gln phosphate

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

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

  19. 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

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

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

  22. d. Summarize

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

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

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

  26. (4) Antagonists of deoxy- nucleotide biosynthesis

  27. 4. Catabolism of purine nucleotides • Process • final product---uric acid (3) gout

  28. 5. Catabolism of pyrimidine Nucleotides *final products

  29. ●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)。

  30. ●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。