The Krebs Cycle

Overview

• Also known as Tricarboxylic Acid (TCA) Cycle or Citric Acid Cycle
• Discovered by Hans Krebs
• Follows Glycolysis and the conversion of Pyruvate to Acetyl-CoA

Glycolysis Recap

• Glucose (6 carbon) -> 2 Pyruvate (3 carbon each)
• Produces 2 NADH and 2 net ATP
• Pyruvate + Coenzyme A -> Acetyl-CoA
  • Produces 2 NADH and 2 CO2 (

Key Steps in the Krebs Cycle

1. Acetyl-CoA + Oxaloacetate (OAA) --> Citrate
   • Enzyme: Citrate Synthase
2. Citrate --> Isocitrate
   • Enzyme: Aconitase
3. Isocitrate --> Alpha-Ketoglutarate (5 carbon)
   • Produces CO2 and NADH
   • Enzyme: Isocitrate Dehydrogenase
4. Alpha-Ketoglutarate --> Succinyl-CoA (4 carbon)
   • Produces CO2 and NADH
   • Enzyme: Alpha-Ketoglutarate Dehydrogenase
5. Succinyl-CoA --> Succinate
   • Produces GTP (converted to ATP)
   • Enzyme: Succinyl-CoA Synthetase
6. Succinate --> Fumarate
   • Produces FADH2
   • Enzyme: Succinate Dehydrogenase
7. Fumarate --> Malate
   • Enzyme: Fumarase
8. Malate --> Oxaloacetate (OAA)
   • Produces NADH
   • Enzyme: Malate Dehydrogenase

Regulation

• Citrate Synthase is inhibited by ATP, NADH, Citrate, and Succinyl-CoA
• Isocitrate Dehydrogenase is inhibited by ATP and stimulated by ADP and Calcium
• Alpha-Ketoglutarate Dehydrogenase is inhibited by Succinyl-CoA and NADH and stimulated by Calcium
• Succinate Dehydrogenase is part of the Electron Transport Chain (ETC) and mutations can lead to conditions like Pheochromocytoma
• Fumarase deficiencies can lead to tumors including leiomyomas
• Malate Dehydrogenase is reversible

Key Products (per turn of the cycle)

• 2 CO2
• 1 ATP (by substrate-level phosphorylation)
• 3 NADH
• 1 FADH2

Total Products (per glucose, 2 turns)

• 4 CO2
• 2 ATP
• 6 NADH
• 2 FADH2

NADH and FADH2

• Carry electrons to the Electron Transport Chain (ETC)
• Used in Oxidative Phosphorylation to produce ATP

Mnemonics

• Citrate Is Krebs' Starting Substrate For Making Oxaloacetate