生物化学原理教学（杨荣武）Chapter23 TCA cycle.pptVIP

Outline Overview of TCA cycle All TCA cycle reactions Summary of the TCA cycle Physiological functions of the TCA cycle The Glyoxylate Cycle Anaplerotic reactions of the TCA cycle Regulation of the TCA cycle Overview of TCA cycle aka Citric Acid Cycle, Krebs Cycle A common metabolic pathway for glucose, aa and fatty acid Pyruvate (actually acetate) from glycolysis is degraded to CO2 Some ATP is produced More NADH is made NADH goes on to make more ATP in electron transport and oxidative phosphorylation Entry into the TCA Cycle Pyruvate Dehydrogenase(PDH) Complex Pyruvate is oxidatively decarboxylated to form acetyl-CoA Pyruvate dehydrogenase uses TPP, CoASH, lipoic acid, FAD and NAD+ Pyruvate dehydrogenase (E1) Dihydrolipoamide transacetylase (E2) Dihydrolipoamide dehydrogenase (E3) Formation of citrate Catalyzed by Citrate Synthase Another example for the induced fit model OAA, the first substrate to bind to the enzyme, induce a large conformational change, creating a binding site for the second substrate, acetyl-CoA. When citroyl-CoA forms on the enzyme surface, another conformational change brings the side of a crucial Asp residue into position to cleavage the thioester. This mechanism decreases the likelihood of premature and unproductive cleavage of the thioester bond of acetyl-CoA Isomerization of Citrate to Isocitrate Catalyzed by Aconitase Citrate is a poor substrate for oxidation So aconitase isomerizes citrate to yield isocitrate which has a secondary -OH, which can be oxidized Note the stereochemistry of the Rxn: aconitase removes the pro-R H of the pro-R arm of citrate! Aconitase uses an iron-sulfur cluster Oxidative Decarboxylation of Isocitrate Catalyzed by Isocitrate Dehydrogenase (IDH) Classic NAD+ chemistry (hydride removal) followed by a decarboxylation Isocitrate dehydrogenase is a link to the electron transport pathway because it makes NADH Know the mechanism! A second oxidative decarboxylation Catalyzed by ? -Ketoglutarate Dehydroge