Human liver debrisoquine 4-hydroxylase: test for specificity toward various monooxygenase substrates and model of the active site.
Polyclonal antibodies raised toward a debrisoquine 4-hydroxylating cytochrome P-450 species purified from rat liver (P-450UT-A) were used to determine which monooxygenase reactions are linked to debrisoquine hydroxylation in human liver. Anti P-450UT-A did not inhibit the oxidation of dimethylnitrosamine, morphine, diazepam, vinylidene chloride, trichloroethylene, benzo(a)pyrene and its 7.8-dihydrodiol, but was inhibitory for the hydroxylation of debrisoquine, (+/-)-bufuralol, lasiocarpine and monocrotaline. A model interpreting the substrate specificity of the human liver enzyme is presented.
D000818:Animals; D001665:Binding Sites; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D051381:Rats; D013379:Substrate Specificity
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6