Merck

Phenylalanine hydroxylase: function, structure, and regulation.

IUBMB life (2013-03-05)
Marte I Flydal, Aurora Martinez
ABSTRACT

Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. In humans, mutations in the PAH gene lead to phenylketonuria (PKU), and most mutations are mainly associated with PAH misfolding and instability. The established treatment for PKU is a phenylalanine-restricted diet and, recently, supplementation with preparations of the natural tetrahydrobiopterin cofactor also shows effectiveness for some patients. Since 1997 there has been a significant increase in the understanding of the structure, catalytic mechanism, and regulation of PAH by its substrate and cofactor, in addition to improved correlations between genotype and phenotype in PKU. Importantly, there has also been an increased number of studies on the structure and function of PAH from bacteria and lower eukaryote organisms, revealing an additional anabolic role of the enzyme in the synthesis of melanin-like pigments. In this review, we discuss these recent studies, which contribute to define the evolutionary adaptation of the PAH structure and function leading to sophisticated regulation for effective catabolic processing of phenylalanine in mammalian organisms.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
6-Biopterin, ≥97%
Sigma-Aldrich
L-Phenylalanine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Phenylalanine, reagent grade, ≥98%
Sigma-Aldrich
L-Phenylalanine, BioUltra, ≥99.0% (NT)
USP
L-Phenylalanine, United States Pharmacopeia (USP) Reference Standard
Supelco
L-Phenylalanine, Pharmaceutical Secondary Standard; Certified Reference Material
Phenylalanine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
L-Phenylalanine, 99%, FCC
Supelco
L-Phenylalanine, analytical standard, for Nitrogen Determination According to Kjeldahl Method
Supelco
L-Phenylalanine, certified reference material, TraceCERT®