Aromatic amino acid metabolism

Phenylalanine & Tyrosine - The Classic Pathway

• Phenylalanine (essential) is converted to Tyrosine (non-essential) by Phenylalanine Hydroxylase (PAH).
• Requires Tetrahydrobiopterin (BH4) as a cofactor. Deficiency in PAH or BH4 leads to Phenylketonuria (PKU).
• PKU features: intellectual disability, seizures, fair skin/hair, and a characteristic mousy/musty odor.
  • 📌 PhenylKetonUria: Pale skin/hair, Krazy (neurotoxic), Urine odor.

• Tyrosine is a precursor for Dopamine, Melanin, and Thyroid hormones.
• Its catabolism proceeds via homogentisate.
• Deficiency of Homogentisate Oxidase causes Alkaptonuria (Ochronosis).

⭐ In Alkaptonuria, urine turns dark/black upon standing due to the oxidation of homogentisic acid. This is a classic exam clue.

Tyrosine's Fates - Pigments, Hormones, & Energy

• Central Hub: Tyrosine, a non-essential amino acid (synthesized from Phenylalanine), is a precursor for several key molecules.
• Metabolic Fates: Can be catabolized into Fumarate (glucogenic) and Acetoacetate (ketogenic).

• Clinical Correlations:
  • Albinism: Deficient Tyrosinase blocks melanin production.
  • Alkaptonuria (Ochronosis): Deficient Homogentisate Oxidase leads to accumulation of homogisic acid.

⭐ Alkaptonuria: Presents with a classic triad: dark urine upon standing, bluish-black discoloration of connective tissues (ochronosis), and debilitating arthritis in adulthood.

Tryptophan's Travels - Serotonin & Niacin

• Tryptophan is a precursor for both Serotonin (neurotransmitter) and Niacin (Vitamin B3).
• Serotonin Synthesis: Requires Tryptophan Hydroxylase (needs BH4) and Aromatic L-amino acid decarboxylase (needs B6).
• Niacin Synthesis: A minor pathway for Tryptophan, but clinically significant. Requires B6.

• Carcinoid Syndrome: Neuroendocrine tumors secrete vast amounts of serotonin.

  • Symptoms: Flushing, diarrhea, bronchospasm, right-sided cardiac fibrosis.

  ⭐ Key diagnostic finding is elevated 24-hour urinary 5-HIAA.

• Pellagra: Niacin deficiency.

  • 📌 "3 D's": Diarrhea, Dermatitis (in sun-exposed areas), Dementia.
  • Can be precipitated by carcinoid syndrome ("tryptophan steal").

• Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (or BH4) deficiency, leading to intellectual disability and a characteristic musty body odor.
• Maternal PKU syndrome can cause microcephaly and congenital heart defects in the fetus, regardless of the fetal genotype.
• Alkaptonuria results from homogentisate oxidase deficiency, causing dark urine upon standing, ochronosis, and debilitating arthritis.
• Tyrosinemia type 1, a fumarylacetoacetate hydrolase deficiency, presents with severe liver failure and a cabbage-like odor.
• Albinism is most commonly due to a tyrosinase defect, which impairs the conversion of tyrosine to melanin.