Heterotropic co-operative effects between amino acid substrates of phenylalanine hydroxylase

Specificity of amino acids as activators and substrates for phenylalanine hydroxylase.

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...

Single amino acid substitution in Bacillus sphaericus phenylalanine dehydrogenase dramatically increases its discrimination between phenylalanine and tyrosine substrates.

Homology-based modeling of phenylalanine dehydrogenases (PheDHs) from various sources, using the structures of homologous enzymes Clostridium symbiosum glutamate dehydrogenase and Bacillus sphaericus leucine dehydrogenase as a guide, revealed that an asparagine residue at position 145 of B. sphaericus PheDH was replaced by valine or alanine in PheDHs from other sources. This difference was prop...

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...

Mechanism of phenylalanine regulation of phenylalanine hydroxylase.

The mechanism of phenylalanine regulation of rat liver phenylalanine hydroxylase was studied. We show that phenylalanine "activates" phenylalanine hydroxylase, converting it from an inactive to active form, by binding at a true allosteric regulatory site. One phenylalanine molecule binds per enzyme subunit; it remains at this site during catalytic turnover and, while there, cannot be hydroxylat...