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[Biochemistry](https://durgical.com/en/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.

**EC number**
[1.14.16.1](https://www.enzyme-database.org/query.php?ec=1.14.16.1)

**Genes**
PAH

**Structure (PDB)**
[1MMK](https://www.rcsb.org/structure/1MMK)

## 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

- [Phenylalanine and tyrosine metabolism](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/)

## Related conditions

- [Phenylketonuria (PKU)](https://durgical.com/en/conditions/phenylketonuria/)

## Related

- [Phenylalanine](https://durgical.com/en/biochemistry/molecules/phenylalanine/)
- [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/)
- [Tetrahydrobiopterin (BH4)](https://durgical.com/en/biochemistry/molecules/tetrahydrobiopterin/)
- [Tyrosine hydroxylase](https://durgical.com/en/biochemistry/enzymes/tyrosine-hydroxylase/)

## 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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [PAH: Phenylalanine-4-hydroxylase (human)](https://www.uniprot.org/uniprotkb/P00439/entry) (UniProt, 2026); [PAH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/pah/) (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](https://www.rcsb.org/structure/1MMK) (RCSB Protein Data Bank, 2026).

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Source: https://durgical.com/en/biochemistry/enzymes/phenylalanine-hydroxylase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/phenylalanine-hydroxylase/