MedSimplified: The Krebs Cycle

Introduction

• The Krebs cycle, also known as the tricarboxylic acid cycle (TCA cycle), is a biochemical pathway for energy generation.
• It involves the oxidation of acetyl-CoA.
• Produces NADH and amino acids.
• Occurs in:
  • Mitochondria of eukaryotes
  • Cytosol of prokaryotes

Steps of the Krebs Cycle

Preparatory Step

• Begins with pyruvate:
  • Derived from glycolysis of glucose (6 carbon compound).
  • Splits into two pyruvate molecules (3 carbon compounds each).
• Pyruvate is oxidized to acetyl CoA:
  • Catalyzed by pyruvate dehydrogenase complex.
  • Produces 1 molecule of CO2 and 1 NADH.
  • Acetyl CoA is a 2 carbon compound.

Main Cycle

1. Formation of Citrate:

   • Acetyl CoA combines with oxaloacetate (4 carbon compound) to form citrate (6 carbon compound).
   • Catalyzed by enzyme citrate synthase.

2. Isomerization to Isocitrate:

   • Citrate is isomerized to isocitrate.
   • Catalyzed by aconitase.

3. Oxidation to Alpha-Ketoglutarate:

   • Isocitrate oxidized to alpha-ketoglutarate (5 carbon compound).
   • Catalyzed by isocitrate dehydrogenase.
   • NAD is reduced to NADH, releasing CO2.

4. Conversion to Succinyl-CoA:

   • Alpha-ketoglutarate converted to succinyl-CoA (4 carbon compound).
   • Catalyzed by alpha-ketoglutarate dehydrogenase.
   • NAD is reduced to NADH, releasing CO2.

5. Conversion to Succinate:

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

6. Oxidation to Fumarate:

   • Succinate converted to fumarate.
   • Catalyzed by succinate dehydrogenase.
   • Generates QH2, used for FADH2 production.

7. Hydration to Malate:

   • Fumarate converted to malate.
   • Catalyzed by fumarase.

8. Oxidation to Oxaloacetate:

   • Malate converted to oxaloacetate.
   • Catalyzed by malate dehydrogenase.
   • NAD is reduced to NADH.

Results of the Krebs Cycle

• For each cycle:
  • 3 NADH
  • 1 FADH2
  • 1 GTP
  • 2 CO2
• Per glucose molecule (cycle runs twice):
  • 6 NADH
  • 2 FADH2
  • 2 GTP
  • 4 CO2

Electron Transport Chain

• NADH and FADH2 are fed to the electron transport chain for ATP generation.

Conclusion

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