An additional substrate binding site in a bacterial phenylalanine hydroxylase

Activation of Phenylalanine Hydroxylase by Phenylalanine Does Not Require Binding in the Active Site

Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at w...

Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation

Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Biochemical and biophysical work has demonstrated that it cycles between two states with a variably low and a high activity, and that the substrate l-Phe is the key player in this transition. X-ray structures of the catalytic domain have shown mobility of a partially ...

Phenylalanine Hydroxylase, Tyrosine Hydroxylase, and Tryptophan Hydroxylase

Mouse phenylalanine hydroxylase. Homology and divergence from human phenylalanine hydroxylase.

The laboratory mouse represents an important model for the study of phenylalanine metabolism and the pathochemistry of phenylketonuria, yet mouse phenylalanine hydroxylase (PAH) has not been extensively studied. We report the cloning and sequencing of a mouse PAH cDNA, the expression of enzymic activity from the mouse PAH cDNA clone and the identification of mouse PAH and human PAH by two-dimen...

Rat liver phenylalanine hydroxylase, an iron enzyme.

Phenylalanine hydroxylase that is essentially pure contains 1 to 2 moles of iron per mole of enzyme (assuming a molecular weight of 100,000). Electron spin resonance (ESR) studies have shown that the iron is present in the high spin ferric form. The addition of substrates (i.e. phenylalanine and dimethyltetrahydropterin) causes the signal for this form to disappear. The iron, 50 to 80%, can be ...