Which enzyme catalyzes the conversion of phenylalanine to tyrosine and is deficient in classic phenylketonuria?

• A. Dihydropteridine reductase
• B. Phenylalanine hydroxylase
• C. Tyrosine aminotransferase
• D. Homogentisate oxidase

Answer: (B)

Phenylalanine hydroxylase is the enzyme that adds a hydroxyl group to phenylalanine to form tyrosine, using tetrahydrobiopterin as a cofactor. In classic phenylketonuria, this enzymatic step is defective, so phenylalanine accumulates in the blood and tissues while tyrosine becomes relatively deficient. The elevated phenylalanine is neurotoxic, which is why untreated classic PKU leads to intellectual disability and developmental problems; treatment focuses on restricting phenylalanine intake to prevent damage. Other enzymes listed have different roles in amino acid metabolism—dihydropteridine reductase helps regenerate the BH4 cofactor and can cause a related form of hyperphenylalaninemia, while tyrosine aminotransferase and homogentisate oxidase act in tyrosine degradation pathways rather than the initial synthesis of tyrosine from phenylalanine.