Effects of sodium fluoride and cobalt chloride on the enantioselectivity of microsomal and cytosolic esterases in rat intestinal mucosa.
The effects of sodium fluoride (NaF) and cobalt chloride (CoCl2) on the enantioselective hydrolysis of racemic oxazepam 3-acetate (rac-OXA) by microsomal and cytosolic esterases in rat intestinal mucosa were studied. Microsomal and cytosolic esterases hydrolyzed S-OXA and R-OXA in approximately 1:19 and 4:1 ratios, respectively. The hydrolysis of R-OXA by microsomal esterases was inhibited by NaF with an IC50 of 13.4 +/- 1.5 mM. Hydrolyses of both S-OXA and R-OXA by cytosolic esterases were inhibited by NaF with a similar IC50 value (approximately 3 mM). The hydrolysis of S-OXA by cytosolic esterases was inhibited by CoCl2 (IC50 = approximately 5 mM), whereas the hydrolysis of R-OXA by cytosolic esterases was stimulated by approximately 10% in the presence of 1 mM CoCl2. In comparison, the hydrolysis of R-OXA by microsomal esterases was stimulated by approximately 55% in the presence of 1 mM CoCl2. These results not only revealed the effects of NaF and CoCl2 on the catalytic activities of enantioselective cytosolic and microsomal esterases, but also indicated that microsomal and cytosolic esterases that selectively hydrolyzed R-OXA were distinctly different protein entities.[1]References
- Effects of sodium fluoride and cobalt chloride on the enantioselectivity of microsomal and cytosolic esterases in rat intestinal mucosa. Yang, S.K., Chang, W.C., Huang, J.D. Biochem. Pharmacol. (1993) [Pubmed]
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