PAH and phenylketonuria: The metabolic defect underlying the classical form of PKU is a mutation in the gene coding for the enzyme phenylalanine hydroxylase (PAH), which is responsible for the conversion of the amino acid Phenylalanine (Phe) into tyrosine. The disrupted metabolism causes accumulation of Phe in the blood, toxic concentrations in the brain, and a reduced level of the amino acid tyrosine.