Transcript Fundamentals of Biochemistry 3/e

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
– NADH
– Acetyl-CoA
• Covalent modification
– Phosphorylation
insulin
Regulation of
TCA Cycle
• Substrate
availability
• Product inhibition
• Competitive
feedback inhibition
Replenishing TCA Cycle