Abstract
The in vitro hepatic O-demethylation of the nonsteroidal estrogen chlorotrianisene (CTA) has been studied. The rate of O-demethylation was maximal at 0.4 mM NADPH. Although NADH did not catalyze the reaction alone, it had a synergistic effect in the presence of equimolar amounts of NADPH. Carbon monoxide decreased the rate of O-demethylation. Nicotinamide was found to decrease the O-demethylation rate at a concentration of 40 mM, but had no apparent effect at concentrations of 20 mM or lower. Extracts from incubation mixtures contained one major (mono-O-demethylated) and a minor (bis-O-demethylated) metabolite. Extracts of mixtures containing soluble rather than microsomal enzymes or from mixtures in which microsomal protein had been denatured did not contain these metabolites.
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