Potent inhibitory effects of tyrosine metabolites on dihydropteridine reductase from human and sheep liver.
L-Phenylalanine and its metabolites, such as phenylpyruvate, phenylacetate and L-phenyllactate, do not significantly inhibit dihydropteridine reductase purified from human and sheep liver (I50 greater than or equal to 5 mM). However, L-tyrosine and its metabolites, such as L-DOPA, tyramine, p-hydroxyphenylpyruvate, p-hydroxyphenylacetate, and p-hydroxyphenylacetate, are potent noncompetitive inhibitors of this enzyme, with Ki values in the range 4-260 microM. These results suggest that tyrosine metabolites can potentially regulate levels of tetrahydrobiopterin, the required cofactor for the hydroxylation of aromatic amino acids.
D000818:Animals; D004093:Dihydropteridine Reductase / Q000037:antagonists & inhibitors*; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010648:Phenylacetates / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D010667:Phenylpyruvic Acids / Q000494:pharmacology; D051381:Rats; D012756:Sheep; D014439:Tyramine / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism / Q000494:pharmacology*
D010648:Phenylacetates; D010666:Phenylpropionates; D010667:Phenylpyruvic Acids; C010590:4-hydroxyphenylpyruvic acid; C001418:4-hydroxyphenyllactic acid; C008070:4-hydroxyphenylacetic acid; D014443:Tyrosine; D010649:Phenylalanine; D004295:Dihydroxyphenylalanine; D004093:Dihydropteridine Reductase; D009247:NADH, NADPH Oxidoreductases; D014439:Tyramine