第七篇代谢及代谢途径英文tca cylce.ppt

The TCA CycleA common metabolic pathway for glucose, aa and fatty acid aka Citric Acid Cycle, Krebs Cycle 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 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) Citrate Synthase Formation of citrate 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 Aconitase Isomerization of Citrate to Isocitrate 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 Aconitase uses an iron-sulfur cluster Is the three-attachment model out of date or does it need to be modified? IDH and Koshland Jr at UC Berkeley In the absence of Mg2+, IDH binds L- Isocitrate more tightly The four-point location model was proposed Isocitrate Dehydrogenase, IDH Oxidative decarboxylation of isocitrate to yield ? -ketoglutarate 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! ? -Ketoglutarate Dehydrogenase Complex A second oxidative decarboxylation This enzyme i