Carboxylesterases: A Multifunctional Enzyme Involved in Pesticide and Lipid Metabolism

Carboxylesterases (CES, EC 3.1.1.1) hydrolyze ester, amide, and carbamate bonds found in xenobiotics and endobiotics. Multiple CES genes exist in mammals with evidence of multiple gene duplication events occurring throughout evolutionary history. Five CES genes are reported in the Human Genome Organization database, although CES1 and CES2 are the best characterized. CES enzymes are promiscuous in that they can metabolize both xenobiotic and endobiotic compounds. Pesticides, such as the pyrethroids, are an important class of xenobiotic substrates that are metabolized by CES, whereas cholesteryl esters, triacylglycerols, and 2-arachidonoylglycerol are examples of endobiotics that are known to be hydrolyzed by CES. Functional studies using selective chemical inhibitors, siRNA, and gene knockout models are providing valuable insights into the physiological functions of CES, and suggest that CES may be a novel target for the treatment of diseases such as diabetes and atherosclerosis. This article will examine the known physiological functions of CES, review the kinetic constants obtained with pyrethroids and recombinant carboxylesterase isoforms, examine interactions between xenobiotics (primarily pesticides) and lipids that occur with CES enzymes, and where possible the implications that these findings have in terms of health and disease.