第23章 核苷酸代謝
第23章 核苷酸代谢
、核苷酸降解代谢 1. Uric acid is the excreted end product of purine catabolism in humans and many other animals For adenosine, the amino group is hydrolyzed before the ribose group is removed For guanosine, the amino group is hydrolyzed after the ribose group is removed Xanthine oxidase, having multiple cofactors (including an FAD, a Mo complex, four different Fe-s clusters), catalyzes the o2-dependent conversion of hypoxanthine to xanthine and xanthine to uric acid
一、核苷酸降解代谢 1. Uric acid is the excreted end product of purine catabolism in humans and many other animals • For adenosine, the amino group is hydrolyzed before the ribose group is removed. • For guanosine, the amino group is hydrolyzed after the ribose group is removed. • Xanthine oxidase, having multiple cofactors (including an FAD, a Mo complex, four different Fe-S clusters), catalyzes the O2 -dependent conversion of hypoxanthine to xanthine and xanthine to uric acid
Uric acid can be further converted to allantoin allantoate urea or Nh4+ in various animals. The deficiency of adenosine deaminase causes the severe immunodeficiency disease in humans (it is likely the accumulated adenosine is converted to datP which inhibits the formation of all dNdps by ribonucleotide reductase) Overproduction of uric acid was revealed to cause gout(痛风) Allopurinol, an inhibitor of xanthine oxidase is used to treat gout
• Uric acid can be further converted to allantoin, allantoate, urea or NH4+ in various animals. • The deficiency of adenosine deaminase causes the severe immunodeficiency disease in humans (it is likely the accumulated adenosine is converted to dATP, which inhibits the formation of all dNDPs by ribonucleotide reductase). • Overproduction of uric acid was revealed to cause gout (痛风). • Allopurinol, an inhibitor of xanthine oxidase, is used to treat gout
Dephosphorylation.O Excreted by Pi GMP nosine HNO Dephosphorylation HoO HgO -OH Uric acid Primates, birds reptiles, insects Deamination HO Guanosine Inosine 402+HO te oxdase Deribosylation h,o Hao Deribosylatio cO Ribose Ribe NHg C c-o Allantoin Most mammals HN HN Hy ypoxanthin °°首首(尿囊素) (keto form) H2N N H2 H2O xanthinekH20+O% oxidase,Hyo NH2CO0 NH2 NH: Oxidatio Allanton Bony fishes Deamination guanine 、黄嘌呤) HO (尿囊酸) HO N COO CHO xanthine H,0 +O2 oxidase →H2O2 Oxidatio Amphibians, Urea cartilaginous 2 H2N-C-NHg HN 2H20 -OH →2 HO N Mar ANHA invertebrates Uric acid 尿
(黄嘌呤) (尿酸) (尿囊素） (尿囊酸) Dephosphorylation Dephosphorylation Deamination Deamination Deribosylation Deribosylation Oxidation Oxidation
OH OH C、已 C N C N C N CH HC C HC C N且 N且 Allopurinol Hypoxanthine (enol form) Allopurinol was designed to be a competitive inhibitor of xanthine oxidase to treat gout by Elion and Hitchings who shared the nobel prize in 19 88 for their discoveries of important principles for drug treatment
Allopurinol was designed to be a competitive inhibitor of xanthine oxidase to treat gout by Elion and Hitchings, who shared the Nobel Prize in 1988 for their discoveries of important principles for drug treatment