The hepatic phenylalanine hydroxylase system is complex, consisting of at least two enzymes and two non-protein cofactors. In classical phenylketonuria (PKU) the affect component has been shown to be the enzyme, phenylalanine hydroxylase. Recently, several variant forms of PKU have been identified which are due to deficiencies of two of the other components of the hydroxylase system, dihydropte...

Recent clinical studies revealed increased phenylalanine levels and phenylalanine to tyrosine ratios in patients suffering from infection, inflammation and general immune activity. These data implicated down-regulation of activity of phenylalanine hydroxylase by oxidative stress upon in vivo immune activation. Though the structural damage of oxidative stress is expected to be comparably small, ...

Tetrahydrobiopterin [(6R)-5,6,7,8-tetrahydro-L-biopterin, H(4)biopterin] is one of several cofactors of nitric oxide synthases (EC 1.14.13.39). Here we compared the action of N(5)-substituted derivatives on recombinant rat neuronal nitric oxide synthase with their effects on dihydropteridine reductase (EC 1.6.99.7) and phenylalanine hydroxylase (EC 1.14.16.1),the well-studied classical H(4)biop...

Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine. Mutations in the human PheOH gene cause phenylketonuria, a common autosomal recessive metabolic disorder that in untreated patients often results in varying degrees of mental retardation. We have determined the crystal structure of hu...

Rat liver phenylalanine hydroxylase can be markedly activated by a variety of different procedures including those that lead to covalent modification of the enzyme, such as limited proteolysis by alpha-chymotrypsin and alkylation of sulfhydryl groups by N-ethylmaleimide, and those that lead to reversible changes, such as the interaction of the enzyme with lysolecithin and related compounds. The...

BACKGROUND Hyperphenylalaninemia is a common inherited metabolic disease that is due to phenylalanine hydroxylase deficiency, and at least half the affected patients have mild clinical phenotypes. Treatment with a low-phenylalanine diet represents a substantial psychosocial burden, but alternative treatments have not been effective. METHODS To explore the therapeutic efficacy of tetrahydrobio...

M I C E homozygous for the dilute-lethal (8) gene have been reported by COLEMAN (1960) and RAUCH and YOST (1963) to have low liver phenylalanine hydroxylase activity. This deficiency in phenylalanine metabolism has been reported to be due to the presence of an inhibitor of the hydroxylase localized in a particulate fraction of liver (15,000 x g sediment). These investigators have pointed out th...

I have previously discussed the idea that the three pterindependent enzymes, phenylalanine (EC 1.14.16. I ) , tyrosine (EC 1.14.16.2) and tryptophan hydroxylase (EC 1.14.16.4), constitute a family of enzymes whose individual members share many properties, both physical and catalytic (Kaufman, 1974). This notion has predictive value since there have been many instances where the discovery of a r...