Enantioselectivity of esterases, contained in 9,000g supernatant fraction (S9) prepared from homogenate of small intestinal mucosa of male Sprague- Dawley rats and the subsequent 105,000g supernatant (cytosol) and pellet (microsomes) prepared from S9, was studied using racemic oxazepam 3-acetate (rac-OXA) as the substrate. Esterases in S9 were enantioselective in hydrolyzing either S-OXA or R-OXA, depending on a particular subcellular preparation. Cytosolic and microsomal esterases had opposite enantioselectivity and selectively hydrolyzed S-OXA and R-OXA, respectively. Enantioselectivity of esterases solubilized from microsomes with Triton X-100 (0.1%, w/v) was identical to that of the membrane-bound microsomal esterases. Cytosolic esterases were more sensitive to temperature than either solubilized or membrane-bound microsomal esterases. In the presence of paraoxon (1 μM), the esterases selective toward R-OXA in both microsomes and S9 were completely inhibited, whereas the esterases selective toward S-OXA in cytosol were inhibited by ~6%. These results indicate that cytosolic and microsomal esterases in rat small intestinal mucosa are distinctly different enzymes, with opposite enantioselectivity in the hydrolysis of rac-OXA.
|Number of pages||7|
|Journal||Drug Metabolism and Disposition|
|Publication status||Published - 1992|
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