Fundamentals of Biochemistry

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Fundamentals of Biochemistry Third Edition Donald Voet • Judith G. Voet • Charlotte W. Pratt Chapter 17 Citric Acid Cycle Copyright © 2008 by John Wiley & Sons, Inc.

Citric Acid Cycle AKA – Kreb’s Cycle or TCA cycle Generate 3 NADH, FADH2, GTP, CoA, 2 CO2 Located in mitocondria Accounts for many intermediates

Pyruvate Dehydrogenase Complex Multienzyme complex Non-covalently bound Advantages Enhanced reaction rates (limited diffusion) Substrate channeling (limited side reactions) Coordinated regulation of all steps Pyruvate dehydrogenase (E1) Dihydrolipoyl transacetylase (E2) Dihydrolipoyl dehydrogenase (E3)

Dihydolipoyl transacetylase (E2) Intact PDH E1 24 – E1 24 – E2 12 – E3

Reaction 1 Decarboxylation of pyruvate

Reaction 2 Hydroxyethyl group transfer

Reaction 3 Transesterification

Reaction 4 Oxidation of E2 by E3

Reaction 5 Oxidation of E3 by FAD

Citrate Synthase

Aconitase

Isocitrate Dehydrogenase

α-Ketogluterate Dehydrogenase

Succinyl-CoA Synthetase

Figure 17-12

Succinate Dehydrogenase

Fumarase (fumarate hydratase)

Malate Dehydrogenase

Net energy production

Regulation of PDH Product inhibition Covalent modification NADH Acetyl-CoA Covalent modification Phosphorylation insulin

Regulation of TCA Cycle Substrate availability Product inhibition Competitive feedback inhibition

Replenishing TCA Cycle

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