Phenylalanine Hydroxylase (PAH)

PKU; PKU1; Phe-4-monooxygenase

SPN	U107
HGNC	8582
MGI	97473
PubMed	17935162
RGD	3248
UniProt	P00439
Wiki	PAH

Phenylalanine hydroxylase is the rate-limiting enzyme of the metabolic pathway which degrades excess phenylalanine. The other substrates in the reaction are molecular oxygen and tetrahydrobiopterin. Tetrahydrobiopterin is a member of the group of redox biochemicals known as pteridines.

PAH is the gene that encodes for phenylalanine hydroxylase. It was the research on phenylalanine hydroxylase by Seymour Kaufman that led to the discovery of tetrahydrobiopterin as a biological cofactor. Phenylalanine hydroxylase is a tetramer composed of four monomers, that is, composed of 4 identical subunits. Each subunit is in turn composed of three domains, a regulatory domain, a catalytic domain, and a tetramerization domain.

Reference

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Hum. Mutat. 11:482-482(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X."
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"Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine."
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Clin. Biochem. 46:1896-1898(2013) [PubMed] [Europe PMC] [Abstract]

"Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among Austrian patients with PAH deficiency: comprehensive results from molecular analysis in 147 patients."
J. Inherit. Metab. Dis. 36:7-13(2013) [PubMed] [Europe PMC] [Abstract]

"Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene."
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