Lecture on TCA Cycle (Citric Acid/Krebs Cycle) - Dirty Biochemistry

Introduction

• Previous Topics Recap:
  • Glycolysis and Gluconeogenesis (Glucose to Pyruvate and vice versa)
  • Pyruvate Metabolism Options:
    • Conversion to Acetyl-CoA for TCA cycle

TCA Cycle Overview

• Also known as Citric Acid Cycle or Krebs Cycle.
• Primary Goal: Generate NADH and FADH2.
  • These molecules are essential for the Electron Transport Chain (ETC) to produce ATP.

Overall Reaction of TCA Cycle

• Reactants: Acetyl-CoA, 3 NAD+, FAD, GDP, Phosphate
• Products: 2 CO2, 3 NADH, 1 FADH2, 1 GTP, 1 CoA

Steps of the TCA Cycle

1. Acetyl-CoA → Citrate
   • Enzyme: Citrate Synthase
2. Citrate → Isocitrate
   • Enzyme: Aconitase
3. Isocitrate → Alpha-Ketoglutarate
   • Enzyme: Isocitrate Dehydrogenase (Rate-Limiting Step)
   • Produces 1 NADH
4. Alpha-Ketoglutarate → Succinyl-CoA
   • Enzyme: Alpha-Ketoglutarate Dehydrogenase
   • Produces 1 NADH
5. Succinyl-CoA → Succinate
   • Enzyme: Succinyl-CoA Thiokinase
   • Produces 1 CoA
6. Succinate → Fumarate
   • Enzyme: Succinate Dehydrogenase
   • Produces 1 FADH2
7. Fumarate → Malate
   • Enzyme: Fumarase
8. Malate → Oxaloacetate
   • Enzyme: Malate Dehydrogenase
   • Produces 1 NADH
   • Oxaloacetate combines with Acetyl-CoA to continue the cycle

Regulation of TCA Cycle

• Stimulants:
  • ADP stimulates the cycle as it indicates low ATP availability requiring an increase in ATP production via ETC.
• Inhibitors:
  • ATP inhibits the TCA cycle as sufficient ATP is a signal to reduce ATP production.
  • NADH and FADH2 provide negative feedback as surplus quantities indicate no immediate need for more production.

Memorization Tips

• Rate Limiting Enzyme: Isocitrate Dehydrogenase
  • Focus on conversion of Isocitrate to Alpha-Ketoglutarate
• Enzymes Naming & Function:
  • Enzyme names generally indicate their substrate and action (e.g., Citrate Synthase synthesizes Citrate).
• NADH Production Mnemonic:
  • Steps with substrates around the letter 'N' in the alphabet produce NADH (Isocitrate 4, Alpha-Ketoglutarate 5, Malate 8).
• FADH2 Production Mnemonic:
  • Fumarate formation coincides with FADH2 production.

Conclusion

• Understand the TCA cycle's role in cellular respiration and ATP production.
• Memorize key enzymes and regulatory elements to grasp how the cycle is controlled and its integration with other metabolic pathways.