Biochemistry · Enzyme
Phenylalanine hydroxylase (PAH) !
Phenylalanine hydroxylase turns phenylalanine into tyrosine in the liver. If it fails, phenylalanine builds up: phenylketonuria.
Updated 2026-11-01
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Key facts
- Phenylalanine + BH4 + O₂ → tyrosine + dihydrobiopterin + H₂O; it needs Fe²⁺.
- It is mainly in the liver (also the kidney); a homotetramer.
- The PAH gene is on chromosome 12 and inheritance is autosomal recessive.
- It is one of the three BH4-dependent aromatic amino acid hydroxylases, with those for tyrosine and tryptophan.
Structure
- 1MMK: the human catalytic domain with Fe²⁺, BH4 and thienylalanine, a phenylalanine analogue.
Regulation
- Phenylalanine activates it by binding its regulatory domain.
- Phosphorylation by PKA (glucagon) increases its activity.
Inhibitors and toxins
- No inhibitors are used clinically.
Clinical notes
- Classic phenylketonuria with almost no activity; milder forms (hyperphenylalaninaemia) keep some activity.
- Some variants respond to sapropterin (BH4).
- Newborn screening measures phenylalanine in a drop of heel blood.
Pathways
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
Which product does phenylalanine hydroxylase make?
Tyrosine; that is why tyrosine becomes essential in phenylketonuria.
Which cofactors does it need?
Tetrahydrobiopterin, molecular oxygen and ferrous iron.
How is deficiency of this enzyme inherited?
Autosomal recessive, from variants in both alleles of the PAH gene.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: PAH: Phenylalanine-4-hydroxylase (human) (UniProt, 2026); PAH gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1MMK: Crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase ((FeII)) complexed with tetrahydrobiopterin and thienylalanine (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.