chapter+30-33+nitrogen+metabolism-2课件.pptVIP

3.2.4 核糖三磷酸和胸苷酸的生物合成 核苷酸与核酸生物合成的关系 PRPP酰胺转移酶：受IMP、AMP和GMP的抑制，受PRPP的激活 腺苷酸代琥珀酸合成酶 次黄嘌呤核苷酸脱氢酶 从头合成和补救合成途径之间的调控 嘌呤核苷酸合成关键酶的调控 3.3 核苷酸生物合成途径的调控 天冬氨酸氨基甲酰转移酶(ATCase)：是细菌中的关键调控酶，受ATP的变构激活，受CTP、UTP抑制 氨甲酰磷酸合成酶（CPS-Ⅱ）：是动物细胞的关键调控酶，受ATP和PRPP激活，受UDP和UTP抑制 嘧啶核苷酸合成关键酶的调控 The biosynthesis of AMP and GMP is regulated by feedback inhibition PRPP synthase and glutamine-PRPP amidotransferase are both inhibited by the end products IMP, AMP and GMP (AMP and GMP act synergistically). AMP inhibits adenylosuccinate synthase and GMP inhibits IMP dehydrogenase. AMP and GMP synthesis is balanced by the following mechanism: GTP is needed for AMP synthesis and ATP for GMP synthesis. The de novo synthesis of AMP and GMP is regulated mainly by sequential feedback Inhibition. Purine and pyrimidine bases can be reconverted into nucleotides via the salvage pathway Adenine phosphoribosyltransferase catalyzes the synthesis of AMP from adenine and PRPP. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the synthesis of GMP and IMP. The lack of HGPRT will cause Lesch-Nyhan syndrome. Pyrimidine bases are recycled in a similar way in microorganisms, but pyrimidine bases does not seem to be salvaged in significant amounts in mammals. Lesch-Nyhan综合症 以行为异常、智力发育缺陷构成的典型临床综合征。高尿酸盐血症引起早期肾脏结石，逐渐出现痛风症状。病因为基因伴性连锁退行性变化导致次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）完全缺乏。 尿囊素酶 ＋H2O 尿囊素 尿囊酸 尿囊酸酶 ＋H2O 尿素 乙醛酸 尿酶 ＋2H2O 4NH3 2CO2 3.1.3 嘌呤的分解 尿酸是人、猿及鸟类等体内嘌呤代谢的最终产物。尿酸因动物的种类而异可进一步分解，成为尿囊素、尿素、乙醛酸及NH3和CO2 尿酸 尿囊素 尿素＋ 乙醛酸 NH3和CO2 尿酸酶 尿囊酶 （非灵长类的哺乳类） （鱼类、两栖类） 尿酶 ＋H2O （甲壳类） 3.1.3 嘌呤的分解 尿素 乙醛酸 腺苷酸 次黄苷酸 腺苷 腺嘌呤 次黄苷 次黄嘌呤 尿酸 尿囊素 黄嘌呤 尿囊酸 鸟嘌呤 3.1.3 嘌呤的分解 gout (痛风) Gout is a disorder in which sodium urate crystals are deposited in and around joints. This deposition, which occurs because of hyperuricemia, causes a form of arthritis. Gout have two forms: primary and secondary Primary Gout is most often caused by genetic defects in purine metabolism. For example: ①ribose-5-phosphate pyrophosphokinase is not effectively r