title: Carboxylesterases: General detoxifying enzymes.
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).
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: M Jason
authors.initials: MJ
authors.lastname: Hatfield
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: Robyn A
authors.initials: RA
authors.lastname: Umans
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Hyatt
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: Carol C
authors.initials: CC
authors.lastname: Edwards
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: Monika
authors.initials: M
authors.lastname: Wierdl
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Tsurkan
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Taylor
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States. Electronic address: phil.potter@stjude.org.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Potter
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D008958:Models, Molecular; D010755:Organophosphates / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D010755:Organophosphates; D002265:Carboxylic Ester Hydrolases
keywords: Carboxylesterase; Expression; Hydrolysis; Organophosphorus compounds; Structure