Human carboxylesterases: a comprehensive review

Abstract

Mammalian carboxylesterases (CEs) are key enzymes from the serine hydrolase superfamily. In the human body, two predominant carboxylesterases (CES1 and CES2) have been identified and extensively studied over the past decade. These two enzymes play crucial roles in the metabolism of a wide variety of endogenous esters, ester-containing drugs and environmental toxicants. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of potent CES modulators to regulate endobiotic metabolism or to improve the efficacy of ester drugs. This review covers the structural and catalytic features of CES, tissue distributions, biological functions, genetic polymorphisms, substrate specificities and inhibitor properties of CES1 and CES2, as well as the significance and recent progress on the discovery of CES modulators. The information presented here will help pharmacologists explore the relevance of CES to human diseases or to assign the contribution of certain CES in xenobiotic metabolism. It will also facilitate medicinal chemistry efforts to design prodrugs activated by a given CES isoform, or to develop potent and selective modulators of CES for potential biomedical applications.

Enhanced Cypermethrin Degradation Kinetics and Metabolic Pathway in Bacillus thuringiensis Strain SG4

“…Metabolites of synthetic pyrethroids have been reported in human urine samples, indicating their toxicity to living systems [8]. The microsomal enzyme carboxylesterase metabolizes these chemicals inside the human body [9].…”

A Conserved Carboxylesterase Inhibits Tobacco mosaic virus (TMV) Accumulation in Nicotiana benthamiana Plants

“…They are enzymes that catalyze the hydrolysis of carboxylic esters into their corresponding alcohols and carboxylic acids [1]. In animals and microbes, many CXEs have been cloned and characterized [2][3][4]. They are involved in a broad range of functions, including processing and degradation of neurotransmitters, hormones, and xenobiotics [5,6].…”

Integrated evolutionary and structural analysis reveals xenobiotics and pathogens as the major drivers of mammalian adaptation

“…We also identified individual positively selected clusters in the members of three other protein families involved in detoxification: glutathione S-transferase alpha 3 47-50 , carboxylesterase 1 51,52 and sulfotransferase 2A1 53,54 . In all cases, positively selected sites cluster around the active site of the enzyme where the substrate binds ( fig.…”