Amino Acid Metabolism and Urea Cycle Overview

Amino Acid Metabolism and Urea Cycle

• Protein Digestion

  • Proteins in diet are broken down through enzymatic processes.
  • Stomach:
  • Hydrochloric acid (HCl) denatures proteins.
  • HCl activates pepsinogen to pepsin which breaks down complex proteins into polypeptides.
  • Pancreas:
  • Proteases (trypsin, chymotrypsin, elastase, carboxypeptidase) break down polypeptides into oligopeptides.
  • Small Intestine:
  • Aminopeptidases further cleave oligopeptides into small peptides and free amino acids absorbed into the liver.

• Catabolism of Amino Acids

  • Involves nitrogen removal, releasing it as ammonia, urea, and uric acid.
  • No storage proteins exist for amino acids; obtained from diet, synthesized de novo, or through protein degradation.

Transamination

• Definition: Removal of nitrogen from amino acids by transferring the α-amino group to α-ketoglutarate, forming glutamate and an α-ketoacid.
• Enzyme: Aminotransferases (e.g., Alanine aminotransferase (ALT), Aspartate aminotransferase (AST)).
• Cofactor: Pyridoxal phosphate.
• Substrates: Pyruvate, oxaloacetate, α-ketoglutarate.

Oxidative Deamination

• Enzyme: Glutamate dehydrogenase.
• Cofactors: Uses NAD+ or NADP+.
• Process: Occurs in liver and kidneys, resulting in α-ketoacids and ammonia (NH3).
• Importance: Ammonia is toxic and converted to urea in the liver.

Urea Cycle

• Purpose: Major disposal form of amino groups from amino acids, primarily derived from ammonia, aspartate, and carbon dioxide.
• Urea Production:
  • Occurs in the liver.
  • Transported to the kidneys for excretion in urine.
• Special Details:
  • Bacterial urease in the intestine can convert urea back to ammonia.

Nitrogen Elimination

• Processes Involved:
  • Transamination, oxidative deamination; the amino group (NH3) is toxic, leading to conversion to urea for urine elimination.

Types of Amino Acids

• Essential Amino Acids: Required from the diet (e.g., phenylalanine, valine, tryptophan).
• Non-Essential Amino Acids: Synthesized by the body (e.g., alanine, glutamate).
• Categories Based on Metabolism:
  • Glucogenic Amino Acids: Yield pyruvate or TCA cycle intermediates (substrates for gluconeogenesis).
  • Ketogenic Amino Acids: Yield acetoacetate or acetyl CoA (substrates for ketogenesis).
  • Some amino acids are both glucogenic and ketogenic.

Amino Acid Biosynthesis Families

• Six Families of Pathways:
  • Glutamate family
  • Aspartate family
  • Serine family
  • Alanine family
  • Aromatic amino acids family
  • Histidine family
• Sources of Pathways:
  • Glutamate: α-ketoglutarate
  • Aspartate: oxaloacetate
  • Serine: 3-phosphoglycerate
  • Alanine: pyruvate
  • Aromatic AAs: other precursors (some not covered).