Metabolism of Individual Amino Acids

Amino Acid Categories & Fates - The Building Blocks

• Essential Amino Acids (AAs): Cannot be synthesized de novo by the body; must be from diet.

  • 📌 Mnemonic: PVT TIM HALL (Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine*, Leucine, Lysine). *Arginine: semi-essential.

• Non-Essential AAs: Can be synthesized by the body.

• Metabolic Fates of Carbon Skeletons:

  Category	Primary Fate	Key Examples (Mnemonic)
  Glucogenic	Forms glucose precursors (pyruvate, TCA intermediates)	Alanine, Serine, Aspartate, Glutamate (most AAs are glucogenic)
  Ketogenic	Forms ketone body precursors (acetyl-CoA, acetoacetate)	Leucine, Lysine
  Both	Forms both types of precursors	Phenylalanine, Isoleucine, Tryptophan, Threonine, Tyrosine (📌 FITTT)

⭐ Purely ketogenic amino acids are Leucine (L) and Lysine (K).

Aromatic Amino Acids - Ring Leaders' Tales

Phenylalanine (Phe) & Tyrosine (Tyr):

• Disorders:
  • PKU: Phenylalanine Hydroxylase (or BH4) def. ↑Phe. 📌 Pale skin, Kinky hair, mousy Urine. Intellectual disability, seizures. Rx: Low Phe diet.
  • Alkaptonuria: Homogentisate Oxidase def. Black urine, ochronosis, arthritis.

  ⭐ Alkaptonuria is due to homogentisate oxidase deficiency, leading to black urine on standing and ochronosis.

  • Tyrosinemia Type I: Fumarylacetoacetate Hydrolase def. Cabbage-like odor, liver failure, renal dysfunction.

Tryptophan (Trp): Essential. Glucogenic & Ketogenic.

• Products: Niacin (B3), Serotonin, Melatonin.
• Hartnup Disease: Defective neutral amino acid transporter. ↓Trp absorption. Pellagra-like symptoms (3Ds: Dermatitis, Diarrhea, Dementia).

Sulphur & Branched-Chain AAs - Chain Reactions & Sulphur Signals

Sulphur AAs: Methionine & Homocysteine Methionine metabolism: SAM (methyl donor), Homocysteine (Hcy). Hcy fates:

Homocystinuria: ↑Hcy. Common: Cystathionine β-synthase (CBS, PLP/B6) defect. Symptoms: Lens dislocation, skeletal issues, thrombosis, ID. Rx: ↓Met, ↑Cys, B6, B12, Folate.

Branched-Chain Amino Acids (BCAAs): Valine, Leucine, Isoleucine

• Catabolism: Muscle. Key: Branched-Chain α-Keto Acid Dehydrogenase (BCKDC).
  • Cofactors: Thiamine (TPP), Lipoate, CoA, FAD, NAD+ (📌 TLC For Nancy).
• MSUD: BCKDC defect. Sweet urine, neurotoxic. 📌 Symptoms: Vomiting, Irritability, Poor feeding, Lethargy (VIP Lounge).
• Products: Val→Succinyl CoA (G); Ile→Acetyl CoA+Succinyl CoA (G/K); Leu→Acetyl CoA+Acetoacetate (K).

⭐ Maple Syrup Urine Disease (MSUD) is caused by a deficiency of the branched-chain α-keto acid dehydrogenase complex (BCKDC).

Other Key Players & Urea Cycle Link - Diverse Roles & Urea Links

• Glycine: Heme, purine, glutathione precursor. Glycine cleavage defect → non-ketotic hyperglycinemia.
• Serine: From 3-phosphoglycerate. Precursor to glycine, cysteine, sphingolipids.
• Methionine: Forms S-adenosylmethionine (SAM) (major methyl donor). Regenerated from homocysteine (needs Vit $B_{12}$/folate).
• Cysteine: From homocysteine & serine. Glutathione component. Tubular reabsorption defect (COLA 📌) → Cystinuria.
• Arginine: Urea cycle intermediate.

  ⭐ Nitric oxide (NO) is synthesized from Arginine by NO synthase.

• Histidine: Decarboxylated to histamine. Histidinemia.
• Urea Cycle Link: Ornithine, Arginine involved. Fumarate connects to TCA cycle.

High‑Yield Points - ⚡ Biggest Takeaways

• Phenylketonuria (PKU): Phenylalanine hydroxylase defect; tyrosine essential; mousy odor.
• Alkaptonuria: Homogentisate oxidase deficiency; ochronosis, dark urine on standing.
• Maple Syrup Urine Disease (MSUD): Deficient branched-chain α-ketoacid dehydrogenase; ↑ BCAAs; sweet urine odor.
• Homocystinuria: Cystathionine β-synthase defect; ↑ homocysteine, methionine; ectopia lentis, thrombosis.
• Tyrosinemia Type I: Fumarylacetoacetate hydrolase defect; cabbage odor; liver/kidney damage.
• Leucine & Lysine: Exclusively ketogenic.
• Hartnup disease: Defective neutral amino acid transport (tryptophan); pellagra-like symptoms.