Effects of Intermediate Metabolites of 37 Xenobiotics on the Catalytic Activities of Reconstituted Cytochrome P-450IIB1 and P-450IA1 Enzyme Systems

摘要

Direct effects of intermediate metabolites of 37 different xenobiotics on the catalytic activities of bothn reconstitute cytochrome P-450ⅡP-45PIA1 enzyme systems were studied by determination of NADPH oxidation at various intervals after initiation of the reaction.The results showed that cytochrome P-4500ⅡB isozyme was much more likely than cytochrome P-450IA1 isozyme to be attacked by the reactive intermediates formed by some xenobiotics with smaller molecular weight and lose its catalytics activities.These xenobiotics were carbon tetrachloride,chloroform,carbon disulfide,benzene,parathion, methylparathion,methyldurshan and dimethylnitrosamine.In contrast,however,steadily increasing metabolic activities were observed toards benzo(a)pyrene,3-methylcholanthrene and polychlorinated biphenyls in reconstituted cytochrome P-450IA1 enzyme system as the reaction time prolonged within 4min.The method discussed in this paper could e be used as a simple and convenient way to observe directly the autocatalytic destruction of P-450 enzymes by soe chemical agents.