核酸的降解与核苷酸代谢要点分析.ppt

核苷酸的功能 核苷酸是核酸生物合成的前体 核苷酸衍生物是许多生物合成的活性中间物，例如：UDP-葡萄糖和CDP-二酯酰甘油分别是糖原和磷酸甘油酯合成的中间物 ATP是生物能量代谢中通用的高能化合物 腺苷酸是三种重要辅酶的组分 某些核苷酸是代谢的调节物质。如：cAMP和cGMP是许多激素引起的胞内信使 核 酸 酶 外切核酸酶对核酸的水解位点 核苷酸的降解 嘌呤碱的分解 嘌呤碱的分解首先是在各种脱氨酶的作用下水解脱去氨基。 脱氨反应也可以在核苷或核苷酸的水平上进行，在动物组织中腺嘌呤脱氨酶的含量极少，而腺嘌呤核苷脱氨酶和腺嘌呤核苷酸脱氨酶的活性极高。 嘌呤碱基的脱氨 嘌呤的分解代谢 尿酸的进一步分解 A CASE STUDY : GOUT A 45-year-old man awoke from sleep with a painful and swollen right great toe. On the previous night he had eaten a meal of fried liver and onions, after which he met with his poker group and drank a number of beers. He saw his doctor that morning, “gouty arthritis” was diagnosed, and some tests were ordered. His serum uric acid level was elevated at 8.0 mg/L (NL7.0 mg/L). The man recalled that his father and his grandfather, both of whom were alcoholics, often complained of joint pain and swelling in their feet. A CASE STUDY : GOUT The doctor recommended that the man use NSAIDs for pain and swelling, increase his fluid intake (but not with alcohol) and rest and elevate his foot. He also prescribed allopurinol (别嘌呤醇). A few days later the condition had resolved and allopurinol had been stopped. A repeat uric acid level was obtained (7.1 mg/L). The doctor gave the man some advice regarding life style changes. Gout ALLOPURINOL IS A XANTHINE OXIDASE INHIBITORA SUBSTRATE ANALOG IS CONVERTED TO AN INHIBITOR, IN THIS CASE A “SUICIDE-INHIBITOR” 腺苷脱氨酶缺乏症Adenosine deaminase deficiency (ADA) ：一种严重的免疫缺陷症，腺苷脱氨酶的缺乏可使T淋巴细胞因代谢产物的累积而死亡，从而导致严重的联合性免疫缺陷症（SCID）。通常导致婴儿出生几个月后死亡。 饮酒与痛风 Adenosine Deaminase Deficiency In purine degradation, adenosine ? inosine Enzyme is Adenosine Deaminase (ADA) ADA deficiency results in SCID Severe Combined Immunodeficiency Selectively kills lymphocytes Both B- and T-cells Mediate much of immune response 嘧啶的分解代谢 概述： 从头合成 基本途径 半合成（补救合成） 嘌呤核苷酸的合成 嘌呤核苷酸的合成 ATP和GTP的合成 嘌呤核苷酸合成的补救途径 嘌呤核苷酸生物合成的调节 Nucleotide Metabolism PURINE RIBONUCLEOTIDES: formed de novo i.e., purines are not initially synthesized as f