Regulation of the Citric Acid Cycle
DIRECT REGULATION OF ENZYMES
- Citrate synthase
- Isocitrate dehydrogenase
- Alpha-ketoglutarate dehydrogenase complex.
- Coupling of citric acid cycle energy intermediates with oxidative phosphorylation
- NADH and FADH2
- Citric acid cycle intermediate
- Inhibits PFK-1
- PFK-1: key regulated enzyme in glycolysis
- Catalyzes the production of citrate.
Inhibition
- Citrate, NADH, ATP, and Succinyl CoA.
Activation
- ADP (and Ca++ in muscles)
- Catalyzes the first decarboxylation
Inhibition
- NADH and ATP
Activation
- ADP (and Ca++ in muscles)
- Catalyzes second decarboxylation
Inhibition
- NADH and succinyl-CoA
Activation
- Ca++ in muscles
- Can enter biosynthetic pathways (i.e. oxaloacetate and malate to gluconeogenesis)
Anaplerotic reactions
- Replenish intermediates of citric acid cycle that are used in biosynthetic pathways
- Amino acids from muscle produce: oxaloacetate, fumarate, succinyl CoA, alpha-ketoglutarate)