Effect of succinate on aminopyrine N-demethylase activity

Succinate stimulated the aminopyrine N-demethylase activity in the presence of rate-limiting concentrations of NADPH in the crude mitochondrial preparation, as well as in a reconstituted system containing microsomes and microsome-free mitochondria. The increase in enzyme activity was accompanied by a decrease of the apparent Km of NADPH. The stimulating effect of succinate was counteracted by malonate, rotenone and pentachlorophenol. No significant formaldehyde oxidation was exhibited by the crude mitochondrial preparation under the conditions of N-demethylase assay. Enhancement of the N-demethylase activity by succinate is supposed to be due to a mitochondrial-microsomal interaction which may play a role in the regulation of drug metabolism.