Comparison between procaine and isocarboxazid metabolism in vitro by a liver microsomal amidase-esterase

Characteristics of a liver microsomal amidase with isocarboxazid (ISOC) as substrate were compared to characteristics of a liver microsomal esterase with procaine (PROC) as substrate. Both amidase and esterase activities were mainly localized in the microsomal fraction with low or null activities in other fractions. Higher specific activities were found in smooth endoplasmic reticulum (s-ER) compared with rough endoplasmic reticulum (r-ER). The microsomal amidase-esterase has a pH optimum of 8.5 to 9.0 and a Km for ISOC of 0.19 mM and for PROC of 0.53 mM. On the basis of sensitivity to certain esterase inhibitors, this amidase-esterase was considered to be a carboxylesterase type; however, no divalent cations were found to activate the amidase-esterase. Since there were no significant differences between ISOC and PROC in their enzymic properties, i.e. subcellular localization, stability, pH optimum and susceptibility to inhibition, it is possible to speculate that this amidase-esterase is responsible for the metabolism of various drugs possessing amido or ester linkage.