Dirty Biochemistry: Pyruvate Metabolism

Introduction

• Pyruvate is a central molecule in metabolic pathways.
• It can transform into four different products, determining the reaction pathway.

Glycolysis and Gluconeogenesis Review

• Glycolysis: Glucose to Pyruvate (shown in red)
• Gluconeogenesis: Pyruvate to Glucose (shown in blue)

Importance of Pyruvate

• Pyruvate acts as a "jack-of-all-trades" in biochemical pathways.
• It can change into four different end products through different pathways.

Pyruvate Pathways

1. Conversion to Lactic Acid (Lactate)

• Pathway: Anaerobic glycolysis (absence of oxygen)
• Enzyme: Lactate dehydrogenase (LDH)
• Conditions: Active in low-oxygen states (e.g., infection, hypoxia, ischemia, heart failure)
• Mnemonic: "Think lactate when you can't make respirations" (T - Testes, L - Lens, W - White blood cells, C - Cornea, M - Medulla of kidney, R - Red blood cells)
• Cofactor: Vitamin B3

2. Conversion to Alanine

• Pathway: Alanine aminotransferase pathway
• Enzyme: ALT (Alanine transaminase)
• Cofactor: Vitamin B6
• Purpose: Part of the Cahill cycle to recycle carbons between muscle and liver
• Cahill Cycle Overview:
  • Pyruvate + Glutamate → Alanine + Alpha-ketoglutarate (muscle)
  • Alanine can travel to liver, converted back to pyruvate
  • Pyruvate converted to glucose through gluconeogenesis
  • Glucose travels back to muscle, converted back to pyruvate

3. Conversion to Oxaloacetate

• Enzyme: Pyruvate carboxylase
• Cofactor: Biotin
• Purpose: Generate oxaloacetate for gluconeogenesis or TCA cycle

4. Conversion to Acetyl CoA

• Importance: Chief reactant of the TCA cycle
• Enzyme: Pyruvate dehydrogenase
• Cofactors: Vitamin B1, B2, B3, B5, Lipoic acid

Key Points

• Anaerobic Glycolysis: Pyruvate to lactic acid, occurs in low oxygen
• Alanine Pathway: Supports the Cahill cycle, transfers carbons
• Oxaloacetate Formation: Supports gluconeogenesis/TCA cycle
• Acetyl CoA Formation: Essential for TCA cycle
• Site of Reactions:
  • Oxaloacetate & Acetyl CoA: Mitochondria (irreversible)
  • Alanine & Lactic acid: Cytosol (reversible)

Conclusion

• Pyruvate metabolism is crucial for cellular energy production.
• All pathways contribute to the electron transport chain for ATP generation.