[Mechanism of the inhibiting effect of the Cu-tyrosine complex on the hydroxylation reactions].
The Cu-tyrosine complex, a low molecular weight analog of superoxide dismutase, exerts an inhibiting effect on cytochrome P-450. The inactivation of cytochrome Y-450 with its transition to cytochrome Y-420 can cause the inhibition by the Cu2+ - Tyr2 complex of dimethylaniline N-demethylation and p-nitroanisol O-demethylation. In case of p-hydroxylation of aniline the inhibiting effect of the Cu-tyrosine complex is much more pronounced than its inactivating effect on cytochrome P-450. In the presence of albumin the complex produced no inactivating effect on cytochrome P-450; under these conditions the inhibiting effect of Cu2+ - Tyr2 on N- and O-demethylation is removed. In case of aniline p-hydroxylation albumin partly decreases the inhibiting effect of the complex on this reaction. In a soluble system containing isolated cytochrome P-450 and cumole hydroperoxide only the aniline p-hydroxylation reaction was found sensitive to the effect of superoxide dismutase. The data obtained suggest participation of the superoxide radical only in aniline p-hydroxylation but not in the reactions of N-demethylation of dimethylaniline and O-dealkylation of p-nitroanisol.
D000818:Animals; D003300:Copper / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D006900:Hydroxylation; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D011817:Rabbits; D013379:Substrate Specificity; D014443:Tyrosine / Q000494:pharmacology*
D014443:Tyrosine; D003300:Copper; D003577:Cytochrome P-450 Enzyme System
Issledovanie mekhanizma ingibiruiushchego deĭstviia med'-tirozinovogo kompleksa na gidroksilaznye reaktsii.