369Lecture14_F11

369Lecture14_F11 - + Lecture 14: Ch 14 The Citric Acid...

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Unformatted text preview: + Lecture 14: Ch 14 The Citric Acid Cycle CH369 Fall 2011 1 + TCA Centrality n Citric acid cycle (TCA cycle; Krebs cycle) is a central pathway n Multiple pathways feed into and from it n Amphibolic n Relates to both catabolism and anabolism n Cyclic metabolic pathway n Glycolysis; gluconeogenesis; pentose phosphate are linear n We’ll look at the significance of this later 2 + Transition Step n Pyruvate dehydrogenase complex n Reaction: pyruvate + CoA + NAD + à acetyl-CoA + CO 2 + NADH n Oxidative carboxylation of pyruvate n Transfer of acetyl unit to coenzyme A (CoA) n Traffic director to control flow of 2-C units from glycolysis into TCA cycle n Complex of 3 enzymes and several coenzymes n Located in mitochondrion n Pyruvate (glycolysis) must move from cytosol to mitochondrion 3 + Pyruvate Dehydrogenase Reactions 4 n Step 1 n Catalyzed by E1 (pyruvate dehydrogenase) n Pyruvate decarboxylated n Involves thiamine pyrophosphate (TPP) cofactor n Thiazolium ring C attacks carbonyl C of pyruvate n CO 2 leaves to form hydroxyethyl-TPP n Stabilized by N + in ring + Pyruvate Dehydrogenase Reactions 5 n Step 2 n Hydroxyethyl group transferred to lipoamide prosthetic group in E2 n E2 = Dihydrolipoyl transacetylase n Breaks disulfide bond of lipoamide n TPP regenerated n Hydroxyethyl oxidized to acetyl + Pyruvate Dehydrogenase Reactions n Step 3 n E2 transfers acetyl group to CoA n Lipoamide now fully reduced n Energy released in oxidation of hydroxyethyl to acetyl is conserved in thioester bond of acetyl-CoA 6 + Pyruvate Dehydrogenase Reactions n Step 4 n E3 reoxidizes lipoamide group of E2 n E3 = Dihydrolipoyl dehydrogenase n Cys-Cys disulfide bond in enzyme is reduced 7 +...
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This note was uploaded on 11/12/2011 for the course CH 369 taught by Professor Kbrowning during the Fall '07 term at University of Texas.

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369Lecture14_F11 - + Lecture 14: Ch 14 The Citric Acid...

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