Phenylalanine hydroxylase (PheH) catalyzes the hydroxylation of dietary phenylalanine to tyrosine. Lack of a functional PheH results in the metabolic disease phenylketonuria (PKU). PheH is one of three aromatic amino acid hydroxylases; the other two are tyrosine hydroxylase and tryptophan hydroxylase. Regulation of PheH is tightly controlled so that only excess phenylalanine is consumed. The enzyme is regulated by activation by phenylalanine, inhibition by tetrahydrobiopterin (BH4), and phosphorylation at Ser16.