Metabolism of Phenylalanine and Tyrosine
- Phenylalanine is an essential amino acid (must be taken from diet).
- In the liver, Phenylalanine is converted to Tyrosine by the enzyme Phenylalanine Hydroxylase.
- This reaction requires:
- Oxygen
- Tetrahydrobiopterin (BH4) as a cofactor.
- Tyrosine therefore becomes conditionally essential (needed if phenylalanine cannot convert to tyrosine).
- Tyrosine is then metabolized to produce several important compounds.
Major Products Derived from Tyrosine
- Catecholamines (Dopamine → Norepinephrine → Epinephrine)
- Requires Vitamin B6, Vitamin C, and SAM in intermediate steps.
- Melanin (skin pigment)
- Tyrosine → DOPA → Melanin
- Enzyme Tyrosinase (deficient in albinism).
- Thyroid hormones (T3 and T4)
- Tyrosine residues on thyroglobulin are iodinated.
- Fumarate and Acetoacetate
- So Tyrosine is both glucogenic (fumarate) and ketogenic (acetoacetate).
Phenylketonuria (PKU)
Cause:
- Deficiency of Phenylalanine Hydroxylase OR deficiency of the cofactor BH4 (less common but more severe).
Consequence:
- Phenylalanine cannot be converted to Tyrosine.
- Phenylalanine accumulates → converted to Phenylpyruvate and other toxic metabolites.
Effects:
- These metabolites cross the blood-brain barrier → interfere with neurotransmitter synthesis.
- Leads to severe developmental issues if untreated.
Clinical features:
- Intellectual disability (if untreated; damage begins in infancy).
- Seizures, microcephaly, developmental delay.
- Hypopigmentation (fair skin, light hair, blue eyes) because Tyrosine is needed for melanin.
- Musty/mousy odor of urine due to phenylacetate.
Treatment:
- Low phenylalanine diet (lifelong).
- Supplement tyrosine (becomes essential).
- Avoid aspartame (contains phenylalanine).
If due to BH4 deficiency → BH4 supplementation.