Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-phenylalanine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an 'inhibitory' domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule. Optimum temperature is 50 degrees Celsius. Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6. Homodimer and homotetramer. Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine. The Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. Phenylalanine hydroxylase entry