Interaction of the serine hydrolase KIAA1363 with organophosphorus agents: Evaluation of potency and kinetics.

ABSTRACT: Oxons are bioactive metabolites of organophosphorus insecticides (OPs) that covalently inactivate serine hydrolases. KIAA1363 is one of the most abundant serine hydrolases in mouse brain. Although the physiological consequences related to the inhibition of KIAA1363 due to environmental exposures to OPs are poorly understood, the enzyme was previously shown to have a role in the detoxification of oxons. Here, we overexpressed human KIAA1363 and CES1 in COS7 cells and compared the potency of inhibition (IC50s, 15 min) of KIAA1363 and CES1 by chlorpyrifos oxon (CPO), paraoxon (PO), and methyl paraoxon (MPO). The order of potency was CPO > PO >> MPO for both enzymes. We also determined the bimolecular rate constants (kinact/Ki) for reactions of CPO and PO with KIAA1363 and CES1. KIAA1363 and C

SUBMITTER: Ross MK 

PROVIDER: S-EPMC4727981 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature