Pyrethroid insecticide hydrolysis carboxylesterases

Vistoli et al. (2010) studied the docking analysis of known substrates to develop both predictive models and molecular dynamics (MD) simulations to identify the in situ behavior of substrates and products. Pyrethroids and their respective carboxylesterase data (Ross et al. 2006) were used as substrates in the training set and in the external test sets for a series of docking experiments. A rich interaction pattern with hCESl was shared by aU the pyrethroid insecticides examined, and explains the marked efficacy with which the esterases hydrolyze the pyrethroids. Molecular dynamics simulations were used to examine the hydrolysis of heroin (CAS no. 561-27-3) to 6-O-acetylmorphine and morphine (CAS no. 57-27-2) by hCESl. 

In an attempt to circumvent the avaUabihty of analytical standards, several CYP450 studies were carried out using the substrate depletion method. This approach does not provide information on the products formed downstream, and may be of limited use in developing human enviromnental exposure PBPK/PD models that require extensive urinary metabolite data. Hydrolytic standards (i.e., alcohols and acids) were available to investigators who studied the carboxylesterase-catalyzed hydrolysis of several pyrethroid insecticides. The data generated in these studies are suitable for use in developing human exposure PBPK/PD models. 

Balance and tissue retention study. J Agric Food Chem 29 130-135 Crawford MJ, Croucher A, Hutson DH (1981b) The metabolism of the pyrethroid insecticide cypermethrin in rats excreted metabolites. Pestic Sci 12 399-411 Crow JA, Borazjani A, Potter PM, Ross MK (2007) Hydrolysis of pyrethroids by human and rat tissues examination of intestinal, liver and serum carboxylesterases. Toxicol Appl Pharmacol 221 1-12... 

There are two types of esterases that are important in metabolizing insecticides, namely, carboxylesterases and phosphatases (also called phosphorotriester hydrolases or phosphotriesterases). Carboxylesterases, which are B-esterases, play significant roles in degrading organophosphates, carbamates, pyrethroids, and some juvenoids in insects. The best example is malathion hydrolysis, which yields both a- and (i-monoacids and ethanol (Figure 8.10). 

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