Nutrition Animal Glycolysis & Krebs Cycle Lecture #6 March 19, 2008 Regulation of Glycolysis Three Glycolysis enzymes catalyze spontaneous reactions: Hexokinase, Phosphofructokinase, Pyruvate Kinase
Control of these enzymes determines the rate of the Glycolysis pathway The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle, and other
pathways
Inner membrane infoldings, called cristae, contain constituents of the respiratory chain
& ATP Synthase. The inner membrane is the major permeability barrier. It contains various transport catalysts, including a carrier protein that allows pyruvate to enter the matrix. Pyruvate Dehydrogenase, catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA. In the overall reaction catalyzed by the Pyruvate Dehydrogenase complex, the acetic acid that is generated is transferred to coenzyme A, and NAD+ is the final electron acceptor. The Kreb's Cycle Three processes play central roles in aerobic metabolism Kreb's cycle, TCA, citric acid cycle Electron transport Oxidative phosphorylation The Kreb's cycle is amphibolic, that is it plays a role in both catabolism and anabolism The Kreb's Cycle Step 1: condensation of acetyl-CoA with oxaloacetate
citrate synthase is an allosteric enzyme, inhibited by both NADH and ATP
The Kreb's Cycle
Step 2: dehydration and rehydration to give isocitrate
The Kreb's Cycle Step 3: oxidation and decarboxylation of isocitrate this is the first oxidation of the cycle, and the first of two molecules of carbon dioxide produced The Kreb's Step Cycle 4: oxidation of -ketoglutarate to succinyl- CoA
-KGDH enzyme is a multienzyme complex and requires coenzyme A, thiamine pyrophosphate, lipoic acid, FAD, and NAD+ The Kreb's Cycle Step 5: formation of succinate
1 energy-yielding step of the cycle GTP functions the same as ATP and yields the same amount of energy
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The Kreb's Cycle Step 6: oxidation of succinate to fumarate
Step 7: hydration of fumarate The Kreb's Cycle Step 8: oxidation of malate Summary of Krebs Cycle (net inputs and outputs, ignoring water and H+): Acetyl CoA + 3 NAD+ + FAD + GDP + Pi 2 CO2 + 3 NADH + FADH2 + GTP + CoA
The 2 carbon atoms of acetate have been fully oxidized to carbon dioxide. (C atoms that
leave as CO2 in each cycle are actually derived from oxaloacetate, a product of the previous cycle) Re-oxidation of NADH and FADH2 via the respiratory chain, to be discussed next, will result in production of additional ~P bonds of ATP Regulation of the Krebs cycle pyruvate dehydrogenase: inhibited by ATP and NADH; also product inhibition by acetyl-CoA
citrate synthase: inhibited by ATP, NADH, and succinyl CoA; also product inhibition by
citrate + isocitrate dehydrogenase: activated by ADP and NAD , inhibited by ATP and NADH ketoglutarate dehydrogenase complex: inhibited by ATP and NADH; activated by ADP and NAD+ The Kreb's cycle in biosynthesis Succinyl CoA is used to synthesize the porphoryin ring of heme a-ketoglutarate and oxaloacetate are used to synthesize amino acids Oxaloacetate is replenished by the carboxylation of pyruvate