chapter9核苷酸代谢.ppt

Nucleotides metabolism 【目的与要求】 记住嘌呤核苷酸有两条合成途径。结合嘌呤核苷酸结构与从头合成途径，说出嘌呤核苷酸各元素或组件的材料来源。熟记二磷酸核苷还原生成脱氧嘌呤核苷酸。写出与嘌呤核苷酸补救合成有关的酶的名称、功能、酶缺陷相关的疾病 结合嘌呤核苷酸合成途径、调节，熟记嘌呤核苷酸抗代谢药物作用机理及临床意义 记住嘌呤核苷酸体内分解代谢终产物-尿酸及其与医学的关系 熟记嘧啶核苷酸从头合成的原料及合成调节。说出嘧啶核苷酸补救合成所需的酶及其催化的反应。明白嘧啶核苷酸抗代谢药物作用机理，记住嘧啶核苷酸分解代谢产物名称 8.1 Purine metabolism -8.1.1 The Biosynthesis of Purines -8.1.2 Purine Salvage -8.1.3 De-oxyribonucleotide Synthesis -8.1.4 Purine Degradation 8.2 Pyrimidine metabolism -8.2.1 Biosynthesis of Pyrimidines -8.2.2 Pyrimidine Degradation Biological Roles of Nucleotides Monomeric units of nucleic acids * “ Energy currency”(ATP) * Regulation of physiological processes Adenosine controls coronary(冠脉) blood flow cAMP and cGMP serve as signaling molecules Precursor function (GTP to tetrahydrobiopternin) Coenzyme components ( 5’-AMP in FAD/NAD+) Activated intermediates: UDP-Glucose Allosteric effectors- regulate themselves and others 思 考？ 8.1.1 Nucleotide Biosynthesis For both purines and pyrimidines there are two means of synthesis - de novo (from bits and parts) - salvage (recycle from pre-existing nucleosides,and bases) Ribose generates energy, but purine and pyrimidine rings do not Nucleotide synthesis pathways are good targets for anti-cancer/antibacterial strategies De novo purine biosynthesis John Buchanan (1948) traced the sources of all nine atoms of purine ring 1. In de novo synthesis, Inosine-5-P (Inosine Monophosphate, IMP) is the first nucleotide formed 2. It is ,then, converted to either AMP or GMP Location: liver cellular Cytoplasm 1. First, synthesis Inosine-5-P (Inosine Monophosphate, IMP) Committed Step 8.1.3 Deoxyribonucleotide Biosynthesis Regulation of dNTP Synthesis The overall activity of ribonucleotide reductase must be regulated Balance of the four deoxynucleotides must be controlled ATP activates, dATP inhibits at the overall activity site ATP, dATP, dTTP and dGTP bind at the