Structural Biochemistry/Enzyme/Phenylalanine Hydroxylase

thumbnail|right|PAH catalyzed hydroxylation reaction. Phenylalanine Hydroxylase (also known as PAH, PheOH, PheH) is an enzyme catalyzing hydroxylation of phenylalanine to make tyrosine. PAH is mainly found in liver and kidneys.Olsson, Elaine et al. "The Aromatic Amino Acid Hydroxylase Mechanism: A Perspective From Computational Chemistry." Theoretical and Computational Inorganic Chemistry 62 (2010): 437- More than 500 mutations have been found for PAH. Mechanism Mechanism of PAH hydroxylation center File:Mechanismpart1.png First part of the PAH mechanism File:Mechanismpart2revised.png Second part of the PAH mechanism Like other aromatic amino acid hydroxylases, PAH follows these steps: FeII-O-O-BH4 bridge formation and cleavage of O-O bond to form FeIV=O complex Attack on FeIV=O to cause hydroxylation of the aromatic amino acid Mutation The most famous example of PAH mutation is related to the genetic disorder phenylketonuria. Patients with PKU have mutation in the PAH gene leading to inactivity of PAH, causing buildup of Phe and subsequent reduced mental development. References