Amino acids

Classification & Groups

• Essential Amino Acids: Must be obtained from the diet.

  • Mnemonic: PVT TIM HALL
  • Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine*, Leucine, Lysine.
  • *Arginine is semi-essential (essential in children, not adults).

• Glucogenic vs. Ketogenic: Refers to the metabolic fate of the carbon skeleton.

  • Exclusively Ketogenic: Can be degraded directly into Acetyl-CoA or Acetoacetate.
    • Leucine & Lysine (the two L’s).
  • Both Glucogenic & Ketogenic:
    • Phenylalanine, Isoleucine, Threonine, Tryptophan, Tyrosine (PITTT).
  • Exclusively Glucogenic: All remaining amino acids. Can be converted to glucose via gluconeogenesis.

• Acidic vs. Basic:

  • Acidic (negatively charged at body pH): Aspartate, Glutamate.
  • Basic (positively charged at body pH): Arginine, Lysine, Histidine. Arginine is the most basic. Histones are rich in arginine and lysine.

• Branched-Chain Amino Acids (BCAAs):

  • Isoleucine, Leucine, Valine (I Love Vermont maple syrup from Branched trees).
  • Metabolized in muscle. Defect causes Maple Syrup Urine Disease.

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High-Yield Derivatives & Functions

• Tryptophan (Trp):

  • → Niacin (Vitamin B3). Requires B6. Deficiency leads to pellagra-like symptoms (e.g., in Hartnup disease).
  • → Serotonin → Melatonin. Requires BH4 and B6.

• Phenylalanine (Phe):

  • → Tyrosine (via phenylalanine hydroxylase; requires BH4).
  • Deficiency leads to Phenylketonuria (PKU).

• Tyrosine (Tyr):

  • → Dopa → Melanin (via tyrosinase). Deficiency → Albinism.
  • → Dopa → Dopamine → Norepinephrine (NE) → Epinephrine (Epi) (Catecholamines).
  • → Thyroxine (Thyroid hormone).

• Histidine (His):

  • → Histamine (via histidine decarboxylase). Requires B6.

• Glycine (Gly):

  • → Porphyrin → Heme (precursor, with Succinyl-CoA). Requires B6.
  • Major inhibitory neurotransmitter in the spinal cord.

• Glutamate (Glu):

  • → GABA (γ-aminobutyric acid; major inhibitory neurotransmitter in the brain). Requires B6.
  • → Glutathione (important antioxidant).

• Arginine (Arg):

  • → Creatine.
  • → Urea.
  • → Nitric Oxide (NO) (vasodilator). Requires BH4.

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Key Associated Disorders

• Phenylketonuria (PKU):

  • Patho: AR; Deficient phenylalanine hydroxylase or BH4 cofactor.
  • Presentation: Intellectual disability, seizures, fair skin/hair, mousy/musty body odor.
  • Dx: Newborn screen (↑ phenylalanine, ↓ tyrosine).
  • Tx: Lifelong dietary restriction of phenylalanine; supplement tyrosine.

• Maple Syrup Urine Disease (MSUD):

  • Patho: AR; Deficient α-ketoacid dehydrogenase → buildup of BCAAs (Isoleucine, Leucine, Valine).
  • Presentation: Sweet-smelling urine/cerumen, poor feeding, vomiting, severe CNS defects, intellectual disability.
  • Tx: Restriction of BCAAs in diet.

• Homocystinuria:

  • Patho: AR; Several causes, most common is cystathionine synthase deficiency.
  • Presentation: Marfanoid habitus, DOWNWARD lens dislocation (vs. upward in Marfan), intellectual disability, thromboembolism, osteoporosis.
  • Tx: ↓ Methionine, ↑ Cysteine, ↑ B6, ↑ B12, and ↑ folate in diet.

• Hartnup Disease:

  • Patho: AR; Defective neutral amino acid transporter in kidneys and intestine.
  • Presentation: Failure to absorb tryptophan, leading to niacin deficiency. Pellagra-like symptoms (dermatitis, diarrhea, dementia/ataxia).
  • Tx: High-protein diet, Niacin supplementation.

• Cystinuria:

  • Patho: AR; Defective dibasic amino acid transporter (Cystine, Ornithine, Lysine, Arginine - COLA).
  • Presentation: Recurrent hexagonal cystine kidney stones.
  • Dx: Urinary cyanide-nitroprusside test is diagnostic.
  • Tx: Urinary alkalinization (e.g., potassium citrate), chelating agents (penicillamine), hydration.