Which enzyme catalyzes the hydroxylation of phenylalanine to tyrosine, and what is the essential cofactor required for this reaction?

Explanation

## Phenylalanine Hydroxylation Reaction **Key Point:** Phenylalanine hydroxylase (PAH) is a hepatic enzyme that catalyzes the first and rate-limiting step in phenylalanine catabolism, converting phenylalanine to tyrosine. ### Enzyme and Cofactor Details | Feature | Detail | | --- | --- | | **Enzyme** | Phenylalanine hydroxylase (PAH) | | **Substrate** | L-Phenylalanine | | **Product** | L-Tyrosine | | **Essential Cofactor** | Tetrahydrobiopterin (BH₄) | | **Tissue Location** | Primarily liver | | **Reaction Type** | Hydroxylation (monooxygenase) | **High-Yield:** Tetrahydrobiopterin (BH₄) is a pteridine cofactor that acts as an electron donor in this hydroxylation reaction. Without adequate BH₄, PAH cannot function, leading to hyperphenylalaninemia even if the PAH gene is intact (variant form of phenylketonuria). **Clinical Pearl:** Deficiency of dihydrofolate reductase (the enzyme that regenerates BH₄ from dihydrofolate) causes a rare form of hyperphenylalaninemia responsive to BH₄ supplementation, distinguishing it from classic PAH deficiency. **Mnemonic:** **PAH-BH₄** — Phenylalanine hydroxylase requires Biopterin (BH₄) as its cofactor.