Potent inhibitory effects of tyrosine metabolites on dihydropteridine reductase from human and sheep liver.

ABSTRACT

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.