Amino Acid Metabolism

Introduction

• Focus on how amino acids are metabolized and used for energy.
• Key processes involve transamination primarily in muscles and subsequent reactions in the liver.

Amino Acids in Muscle

• Alanine Structure:
  • Basic structure: N-C-C backbone with NH3+, a-methyl group, and carboxyl group.
  • Zwitterion form, is neutral overall.

Transamination Process

• Key Molecules:
  • Alanine
  • Alpha-Ketoglutarate (AKG): Derived from glutamate with a double-bonded oxygen instead of NH3 group.
• Enzyme: Alanine Aminotransferase (ALT) or transaminase.
  • Transfers amine group from alanine to AKG, forming pyruvate and glutamate.
  • Coenzyme: Pyridoxal phosphate (derived from Vitamin B6).

Reaction Details

• Alanine + AKG ➔ Pyruvate + Glutamate
  • Pyruvate can convert into lactic acid or acetyl-CoA.
  • Acetyl-CoA enters the Krebs cycle and eventually the electron transport chain for ATP production.
• Cori Cycle: Lactic acid ➔ Pyruvate ➔ Glucose (via gluconeogenesis in liver).
  • Enzyme: Glucose-6-phosphatase.

Glutamate and the Liver

• Process: Oxidative Deamination
  • Enzyme: Glutamate Dehydrogenase
  • Converts NADP+ into NADPH (used in fatty acid synthesis and radical reactions).
  • Glutamate converts to alpha-ketoglutarate, releasing ammonia.
• Ammonia management:
  • Binds with protons to form ammonium.
  • Enter mitochondria, participate in the urea cycle (to be discussed further).

Aspartate Transamination

• Key Molecules:
  • Aspartate: Similar to glutamate but with one less CH2 group.
  • Enzyme: Aspartate Aminotransferase.
• Reaction: Aspartate + AKG ➔ Oxaloacetate + Glutamate
• Reversibility: Reaction is reversible, allowing amino acids to enter the Krebs cycle or gluconeogenesis.

Amino Acid Conversion in Krebs Cycle

• Various amino acids can convert into Krebs cycle intermediates:
  • E.g., Tyrosine to fumarate, Valine to succinyl-CoA, Leucine to acetyl-CoA.
• Significance:
  • Contributes to ATP production.
  • Gluconeogenesis: non-carbohydrate sources converted to glucose.

Clinical Relevance

• Diagnostic Indicators:
  • Enzyme leakage (ALT, AST) from liver or muscle damage.
  • Elevated levels could indicate liver damage or myocardial infarction.

Next Steps

• Upcoming discussion on the urea cycle and the management of ammonia toxicity.