Chm 635-6

Chm 635-6 - Overview of catabolism Entry of Pyruvate into...

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1 Overview of catabolism Entry of Pyruvate into the Mitochondrion ( Transition reaction occurs in mitochondria ) • Pyruvate translocase transports pyruvate into the mitochondria in symport with H +
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2 Transition Reaction The transition reaction connects glycolysis to the citric acid cycle. Pyruvate is converted to acetyl CoA and CO 2 is released. During this oxidation reaction, NAD + is converted to NADH + H + The transition reaction occurs twice per glucose molecule. Thiamine, Riboflavin, Lipoic acid, Niacin and Pantothenate
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3 12.2 Conversion of Pyruvate to Acetyl CoA • Pyruvate dehydrogenase complex (PDH complex) is a multienzyme complex containing: 3 enzymes + 5 coenzymes + other proteins (+ ATP coenzyme as a regulator) E 1 = pyruvate dehydrogenase E 2 = dihydrolipoamide acetyltransferase E 3 = dihydrolipoamide dehydrogenase
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4 The Coenzymes and Prosthetic Groups of Pyruvate Dehydrogenase. http://www.iubmb-nicholson.org/swf/e1_v7.swf
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5 The Coenzymes of the Pyruvate Dehydrogenase Complex Thiamine pyrophosphate TPP assists in the decarboxylation of α -keto acids (here) and in the formation and cleavage of α -hydroxy ketones (as in the transketolase reaction; see Chapter 22). The five steps of the PDH complex Step 1: Catalyzed by E 1
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6 Step 2: The second step is also catalyzed by E 1 Step 3: E 2 transfers the lipoamide-bound acetyl group to HS-CoA forming acetyl CoA
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7
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8 Step 4: E 3 FAD group oxidizes reduced lipoamide of E 2 forming FADH 2
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9 Step 5: E 3 -FADH 2 reduces NAD + to regenerate E 3 -FAD and NADH • The oxidation of E 3 -FADH 2 regenerates the original holoenzyme completing the catalytic cycle • NADH dissociates from the complex E 3 -FADH 2 + NAD + E 3 -FAD + NADH + H +
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10 The five reactions of the PDC. 4600 kD polyhedral particle Pyruvate Dehydrogenase Multienzyme Complex Regulation of the PDH complex • Increased levels of acetyl CoA and NADH inhibit E 2 , E 3 in mammals and E. coli
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11 Factors controlling the activity of the PDC.
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Chm 635-6 - Overview of catabolism Entry of Pyruvate into...

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