糖代谢2-TCAcycle概要.ppt

第八章 糖代谢 第三节 TCA循环 第三节 TCA循环 三羧酸循环（Tricarboxylic Acid Cycle or Citric Acid Cycle or Krebs Cycle）的生理意义 丙酮酸的氧化脱羧 三羧酸循环的化学途径 回补反应 三羧酸循环的调节 丙酮酸脱氢酶复合体 —连接糖酵解与TCA循环的桥梁 Step 1 The methyl carbon of acety-CoA joins the carbonyl carbon of oxaloacetate via aldol condensation to form citrate (柠檬酸); citroyl-CoA is a transiently intermediate but hydrolyzed immediately in the active site of citrate synthase; hydrolysis of the thioester bond releases a large amount of free energy, driving the reaction forward; large conformational changes occur after oxaloacetate is bound and after citroyl-CoA is formed, preventing the undesirable hydrolysis of acetyl-CoA. 葡萄糖有氧氧化过程中ATP的合成 回补反应 1.丙酮酸羧化支路 2.乙醛酸循环支路 3.其他途径 1. 丙酮酸羧化支路 3. 其他途径 某些氨基酸通过转氨基作用生成草酰乙酸或?-酮戊二酸等 * * TCA循环 为生物合成提供原料 TCA循环 是燃料物质氧化分解的中心途径 TCA循环的净结果是： 乙酸(carried by CoA)被氧化生成2CO2，同时合成1ATP，3NADH和1FADH2。 The 4-carbon oxaloacetate (草酰乙酸) acts as the “carrier” for the oxidation. The two carbons released as 2 CO2 in the first cycle of oxidation are not from the acetyl-CoA just joined. The 8 electrons released are collected by three NAD+ and one FAD. One molecule of ATP (or GTP) is produced per cycle by substrate-level phosphorylation. Pyruvate is first transported into mitochondria via a specific transporter on the inner membrane. Pyruvate is converted to acetyl-CoA and CO2 by oxidative decarboxylation. The pyruvate dehydrogenase complex is a huge multimeric assembly of three kinds of enzymes, having 60 subunits in bacteria and more in mammals. Electron micrograph of pyruvate dehydrogenase complexes from E. coli E2 (dihydrolipoyl transacetylase): consisting the core, 24 subunits; E1 (pyruvate dehydrogenase): bound to the E2 core, 24 subunits; E3 (dihydrolipoyl dehydrogenase): bound to the E2 core, 12 subunits. 三羧酸循环的途径 Step 2 Citrate is isomerized into isocitrate (get the six-carbon unit ready for oxidative decarboxylation) via a dehydration step followed by a hydration step; cis-aconitate (顺乌头酸) is an intermediate during