[Use of inhibition by metyrapone in a "mutual depletion system" for evaluation of active centres of various arylhydrocarbon hydroxylases].
It was shown that metyrapone, the inhibitor of arylhydrocarbonhydroxylase, taken at concentrations equimolar to that of cytochrome P-450 non-competitively inhibits the hydroxylation of 3,4-benzpyrene in the liver microsomes of inbred mice of the C57BL/6 and AKR strains. In a given "mutual depletion inhibition system" the concentration of the catalytically active centres of microsomal cytochrome (Ecac), their turnover number (TNcac) and "true" dissociation constant of the enzyme-inhibitor complex were determined in the control and 3-methylcholanthrenetreated mice of both strains. The increased rate of 3,4-benzpyrene hydroxylation in the liver of 3-methylcholanthrene-induced "sensitive" C57BL/6 mice is determined by the increase of Ecac (and, in a lesser degree, of TNcac) per molecule of cytochrome P-448. In the liver microsomes of "induction-resistant" AKR mice an injection of 3-methylcholanthrene results in a slight increase of Ecac and a simultaneous decrease of TNcac. It was assumed that contrary to the present-day concepts, an aberrant microsomal hemoprotein with a genetically determined low molecular activity is synthesized in mice of "resistant" AKR strain.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D003580:Cytochromes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology*; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011485:Protein Binding; D013045:Species Specificity
D003580:Cytochromes; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases; D008797:Metyrapone
Ispol'zovanie ingibirovaniia metiraponom v sisteme so vzaimnym istoshcheniem dlia otsenki aktivnykh tsentrov razlichnykh arilgidrokarbongidroksilaz.