Structural Biochemistry/Enzyme/Phenylalanine Hydroxylase

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.^[1] More than 500 mutations have been found for PAH.^[1]

Mechanism edit

Mechanism of PAH hydroxylation

First part of the PAH mechanism
Second part of the PAH mechanism

Like other aromatic amino acid hydroxylases, PAH follows these steps:

Fe^II-O-O-BH₄ bridge formation and cleavage of O-O bond to form Fe^IV=O complex
Attack on Fe^IV=O to cause hydroxylation of the aromatic amino acid

Mutation edit

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 edit

↑ ^a ^b Olsson, Elaine et al. "The Aromatic Amino Acid Hydroxylase Mechanism: A Perspective From Computational Chemistry." Theoretical and Computational Inorganic Chemistry 62 (2010): 437-

[AAH_Mechanism-1] Olsson, Elaine et al. "The Aromatic Amino Acid Hydroxylase Mechanism: A Perspective From Computational Chemistry." Theoretical and Computational Inorganic Chemistry 62 (2010): 437-

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