Medsimplified Lecture: Krebs Cycle

Overview

• Krebs Cycle
  • Also known as the Tricarboxylic Acid Cycle (TCA cycle)
  • A biochemical pathway that generates energy through oxidation of acetyl CoA
  • Synthesizes NADH and produces amino acids
  • Occurs in the mitochondria of eukaryotes and cytosol of prokaryotes

Preparatory Step

• Begins with pyruvate derived from glycolysis of glucose (6-carbon compound split into two 3-carbon pyruvates)
• Oxidation of Pyruvate
  • Converted into acetyl CoA by pyruvate dehydrogenase complex
  • Generates a molecule of carbon dioxide and NADH

Steps of the Krebs Cycle

1. Formation of Citrate

   • Acetyl CoA (2-carbon) combines with oxaloacetate (4-carbon) to form citrate (6-carbon)
   • Catalyzed by citrate synthase

2. Isomerization

   • Citrate is isomerized into isocitrate by aconitase

3. Oxidation to Alpha-Ketoglutarate

   • Isocitrate oxidized into alpha-ketoglutarate (5-carbon)
   • Catalyzed by isocitrate dehydrogenase
   • Produces NADH and carbon dioxide

4. Conversion to Succinyl-CoA

   • Alpha-ketoglutarate converted into succinyl-CoA (4-carbon)
   • Catalyzed by alpha-ketoglutarate dehydrogenase
   • Produces NADH and carbon dioxide

5. Formation of Succinate

   • Succinyl-CoA converted into succinate
   • Catalyzed by succinyl-CoA synthase
   • Generates GTP

6. Conversion to Fumarate

   • Succinate converted into fumarate by succinate dehydrogenase
   • Generates QH2, used for production of FADH2

7. Formation of Malate

   • Fumarate converted into malate by fumarase

8. Regeneration of Oxaloacetate

   • Malate converted into oxaloacetate by malate dehydrogenase
   • Produces NADH

Products of the Krebs Cycle

• For each cycle:
  • 3 NADH
  • 1 FADH2
  • 1 GTP
  • 2 CO2
• Since glucose splits into two pyruvates, the cycle runs twice per glucose molecule:
  • Total: 6 NADH, 2 FADH2, 2 GTP, 4 CO2
• NADH and FADH2 fed into the electron transport chain to generate ATP