Carboxylesterase: specificity and spontaneous reactivation of an endogenous scavenger for organophosphorus compounds

Journal of Applied Toxicology : JAT
D M Maxwell, K M Brecht

Abstract

The ability of carboxylesterase (CaE) to act as a bioscavenger to provide protection against organophosphorus (OP) compounds has been demonstrated in several animal models. To further evaluate the effectiveness of CaE as a bioscavenger, the specificity and stoichiometry of the detoxication of OP compounds by rat plasma CaE were examined. The specificity of CaE was evaluated by determining the bimolecular rate constants for inhibition (k(i)) of CaE by a variety of OP compounds. CaE exhibited a broad specificity for neutral OP compounds with k(i) > 10(6) M(-1) x min(-1) for paraoxon, sarin, soman, diisopropyl fluorophosphate, and diphenyl p-nitrophenyl phosphinate. CaE exhibited poor reactivity (k(i) < 10(4) M(-1) x min(-1)) with cationic OP compounds, such as echothiophate, VX, and iso-OMPA. The stoichiometry of CaE detoxication of OP compounds was evaluated by determining the rates of enzyme reactivation and ageing of OP-inhibited CaE. CaE exhibited no ageing after inhibition by any of the OP compounds, including soman. However, OP-inhibited CaE did exhibit spontaneous reactivation with reactivation rates that decreased as the size of the OP increased (i.e., VX > sarin > soman). The pH dependence of the spontaneous reactivation...Continue Reading

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Citations

Jan 15, 2013·Archives of Toxicology·Teresa R SternerJeffery M Gearhart
May 7, 2013·Chemico-biological Interactions·Yingling WeiJiale Huang
Jul 3, 2013·Chemico-biological Interactions·Florian NachonPatrick Masson
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