糖代谢2-TCAcycle

Step 8 Oxaloacetate is regenerated by the oxidation of L-malate; this reaction is catalyzed by malate dehydrogenase with two electrons collected by NAD+.
Step 5 Succinyl-CoA is hydrolyzed to succinate (琥珀酸 或戊二酸); the free energy released by hydrolyzing the thioester bond is harvested by a GDP or an ADP to form a GTP or an ATP by substrate-level phosphorylation; the reversible reaction is catalyzed by succinyl-CoA synthetase (or succinic thiokinase);
Step 2 Citrate is isomerized into isocitrate (get the sixcarbon unit ready for oxidative decarboxylation) via a dehydration step followed by a hydration step; cisaconitate (顺乌头酸) is an intermediate during this transformation, thus the catalytic enzyme is named as aconitase, which contains a 4Fe-4S iron-sulfur center directly participating substrate binding and catalysis.
Step 7 Fumarate is hydrated to L-malate（苹果 酸） by the action of fumarase; the enzyme is highly stereospecific, only act on the trans and L isomers, not on the cis and D isomers (maleate and D-malate);
三 羧 酸 循 环 的 途 径

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 acetylCoA.
Step 4 a-ketoglutarate undergoes another round of oxidative decarboxylation; decarboxylated first, then oxidized to form succinyl-CoA (琥珀酰辅酶A); again the carbon released as CO2 is not from the acetyl group joined; catalyzed by a-ketoglutarate dehydrogenase complex; reactions and enzymes closely resemble pyruvate dehydrogenase complex (with similar E1 and E2, identical E3).
•Step 3 Isocitrate is first oxidized and then
decarboxylated to form a-ketoglutarate (a-酮 戊二酸); oxalosuccinate is an intermediate; two electrons are collected by NAD+; the carbon released as CO2 is not from the acetyl group joined; catalyzed by isocitrate dehydrogenase.
乙醛酸循环 Glyoxylate Cycle II
• 异柠檬酸裂解酶（Isocitrate lyase） 催化异 柠檬酸裂解产生乙醛酸（glyoxylate）和琥 珀酸（succinate） • 苹果酸合酶（Malate synthase）催化乙醛酸 和乙酰-CoA 结合生成苹果酸 • 乙醛酸循环体（Glyoxysomes）借用线粒体 （mitochondria）中的三步反应：succinate to oxaloacetate • The glyoxylate cycle helps plants grow in the dark!
葡萄糖有氧氧化过程中ATP的合成
回补反应
TCA循环本身并没有使循环中间体浓度发生改变



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
2. 乙醛酸循环 The Glyoxylate Cycle
A variant of TCA for plants and bacteria • 植物（plants）、藻类（algae）和某些细菌 （bacteria）通过乙醛酸循环途径可以利用乙 酸作为唯一碳源和能源 • 动物组织没有乙醛酸循环，不能将脂肪酸转 变为糖类 • 异柠檬酸裂解酶（Isocitrate lyase）和苹果酸 合酶（malate synthase）是乙醛酸循环特有的 两种酶
Step 6 Succinate is oxidized to fumarate (延胡索酸或反 丁烯二酸); catalyzed by a flavoprotein succinate dehydrogenase (with a covalently bound FAD and three iron-sulfur centers), which is tightly bound to the inner membrane of mitochondria; malonate (丙二酸) is a strong competitive inhibitor of the enzyme, that will block the whole cycle.
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.
TCA循环 为生物合成提供原料
TCA
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 acetylCoA 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.
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
是 燃 料 物 质 氧 化 分循 解环 的 中 心 途 径
3. 其他途径

某些氨基酸通过转氨基作用生成草酰ห้องสมุดไป่ตู้酸 或a-酮戊二酸等
三羧酸循环的调节 Regulation of the TCA Cycle
Again, 3 reactions are the key sites • 柠檬酸合酶（Citrate synthase - ATP, NADH and succinyl-CoA inhibit） • 异柠檬酸脱氢酶（Isocitrate dehydrogenase - ATP inhibits, ADP and NAD+ activate） a -酮戊二酸脱氢酶复合体（a -Ketoglutarate dehydrogenase - NADH and succinyl-CoA inhibit, AMP activates） • Also note pyruvate dehydrogenase: ATP, NADH, acetyl-CoA inhibit, NAD+, CoA activate .