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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Dihydropteridine Reductase / antagonists & inhibitors*
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Dihydroxyphenylalanine / pharmacology
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Humans
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NADH, NADPH Oxidoreductases / antagonists & inhibitors*
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Phenylacetates / pharmacology
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Phenylalanine / pharmacology
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Phenylpropionates / pharmacology
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Phenylpyruvic Acids / pharmacology
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Rats
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Sheep
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Tyramine / pharmacology
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Tyrosine / metabolism
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Tyrosine / pharmacology*
Substances
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Phenylacetates
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Phenylpropionates
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Phenylpyruvic Acids
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4-hydroxyphenylpyruvic acid
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4-hydroxyphenyllactic acid
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4-hydroxyphenylacetic acid
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Tyrosine
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Phenylalanine
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Dihydroxyphenylalanine
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Dihydropteridine Reductase
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NADH, NADPH Oxidoreductases
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Tyramine