Amino acids

I. Metabolic Fate:

• Glucogenic: Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Histidine, Methionine, Proline, Serine, Valine. (Form glucose precursors).
• Ketogenic (Purely): Leucine, Lysine (the 2 "L"s). (Form acetyl-CoA/acetoacetate).
• Both: Phenylalanine, Isoleucine, Threonine, Tryptophan, Tyrosine (Mnemonic: PITTT).

II. Key Amino Acid Disorders:

• Maple Syrup Urine Disease (MSUD):
  • AAs: Branched-chain AAs (BCAAs) - Isoleucine, Leucine, Valine ("I Love Vermont maple syrup").
  • Defect: Branched-chain α-ketoacid dehydrogenase (needs B1 - Thiamine).
  • Features: Sweet-smelling urine, neurotoxicity.
• Propionic Acidemia:
  • AAs (precursors): Valine, Odd-chain FAs, Methionine, Isoleucine, Threonine ("VOMIT").
  • Defect: Propionyl-CoA carboxylase (needs B7 - Biotin).
  • Features: Metabolic acidosis, hyperammonemia.
• Phenylketonuria (PKU):
  • AA: Phenylalanine.
  • Defect: Phenylalanine hydroxylase (or BH4 cofactor). Tyrosine becomes essential.
  • Features: Intellectual disability, "mousy" odor, fair skin.
• Alkaptonuria:
  • Pathway: Tyrosine degradation.
  • Defect: Homogentisate oxidase.
  • Features: Dark urine on standing, ochronosis (dark cartilage), arthritis.
• Homocystinuria:
  • AA: Methionine/Homocysteine.
  • Defect: Often Cystathionine β-synthase (needs B6); others affect B12/folate.
  • Features: Marfanoid habitus, lens subluxation (down & in), thromboembolism, intellectual disability.
• Cystinuria:
  • AAs: Defective renal/intestinal transport of Cystine, Ornithine, Lysine, Arginine ("COLA").
  • Features: Recurrent hexagonal cystine kidney stones.

III. Essential Amino Acids:

• Must be from diet: Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine (conditionally), Leucine, Lysine (Mnemonic: "PVT. TIM HALL").

IV. Key Precursor Roles:

• Tryptophan → Serotonin, Melatonin, Niacin (B3)
• Tyrosine → Catecholamines (Dopamine, NE, Epi), Thyroid Hormones, Melanin
• Glutamate → GABA, Glutathione
• Glycine → Heme, Purines, Creatine, Glutathione
• Arginine → Nitric Oxide, Urea, Creatine
• Histidine → Histamine

V. Unique Structural/Functional Roles:

• Proline: Rigid ring; helix breaker; found in turns.
• Glycine: Smallest (H as R-group); flexible; found in turns.
• Cysteine: Sulfhydryl (-SH) group forms disulfide bonds (protein stability).
• Methionine: Sulfur-containing; S-adenosylmethionine (SAM) is a methyl donor.
• Basic AAs (Lysine, Arginine, Histidine): Positively charged. Histones (Arg, Lys) bind DNA. Histidine often in enzyme active sites (proton transfer).
• Acidic AAs (Aspartate, Glutamate): Negatively charged. Often in enzyme active sites.