Carboxylesterases: General detoxifying enzymes. (25th November 2016)

• Record Type: Journal Article
• Authors: Hatfield, M. Jason; Umans, Robyn A.; Hyatt, Janice L.; Edwards, Carol C.; Wierdl, Monika; Tsurkan, Lyudmila; Taylor, Michael R.; Potter, Philip M.
• Is Part Of: Chemico-biological interactions. Volume 259:Part B(2016)
• Page Start: 327
• Page End: 331
• Publication Date: 2016-11-25
• Subjects: Carboxylesterase -- Expression -- Organophosphorus compounds -- Structure -- Hydrolysis; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2016.02.011
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Carboxylesterases (CE) are members of the esterase family of enzymes, and as their name suggests, they are responsible for the hydrolysis of carboxylesters into the corresponding alcohol and carboxylic acid. To date, no endogenous CE substrates have been identified and as such, these proteins are thought to act as a mechanism to detoxify ester-containing xenobiotics. As a consequence, they are expressed in tissues that might be exposed to such agents (lung and gut epithelia, liver, kidney, etc.). CEs demonstrate very broad substrate specificities and can hydrolyze compounds as diverse as cocaine, oseltamivir (Tamiflu), permethrin and irinotecan. In addition, these enzymes are irreversibly inhibited by organophosphates such as Sarin and Tabun. In this overview, we will compare and contrast the two human enzymes that have been characterized, and evaluate the biology of the interaction of these proteins with organophosphates (principally nerve agents). Highlights: Carboxylesterase are general detoxifying enzymes that hydrolyze esterified molecules. They are expressed in tissues likely to be exposed to such agents. Humans and small mammals demonstrate different levels of carboxylesterase expression. Organophosphorus compounds are irreversibly inhibitors of these enzymes.