Liver carboxylesterase 1

Definition:

Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate. Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins. Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process. First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile.

References:

[1]. Bin Zhao, et al. Redistribution of macrophage cholesteryl ester hydrolase from cytoplasm to lipid droplets upon lipid loading. J Lipid Res. 2005 Oct;46(10):2114-21. [Content Brief]

[2]. S Ghosh, et al. Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA. Physiol Genomics. 2000 Jan 24;2(1):1-8. [Content Brief]

[3]. Bin Zhao, et al. Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport. J Lipid Res. 2008 Oct;49(10):2212-7. [Content Brief]

[4]. J Allen Crow, et al. Inhibition of carboxylesterase 1 is associated with cholesteryl ester retention in human THP-1 monocyte/macrophages. Biochim Biophys Acta. 2008 Oct;1781(10):643-54. [Content Brief]

[5]. R Schindler, et al. Purification and characterization of retinyl ester hydrolase as a member of the non-specific carboxylesterase supergene family. Eur J Biochem. 1998 Feb 1;251(3):863-73. [Content Brief]

[6]. E V Pindel, et al. Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. J Biol Chem. 1997 Jun 6;272(23):14769-75. [Content Brief]

[7]. Bin Zhao, et al. Stable overexpression of human macrophage cholesteryl ester hydrolase results in enhanced free cholesterol efflux from human THP1 macrophages. Am J Physiol Cell Physiol. 2007 Jan;292(1):C405-12. [Content Brief]

[8]. Shuqi Xie, et al. Inactivation of lipid glyceryl ester metabolism in human THP1 monocytes/macrophages by activated organophosphorus insecticides: role of carboxylesterases 1 and 2. Chem Res Toxicol. 2010 Dec 20;23(12):1890-904. [Content Brief]

[9]. M R Brzezinski, et al. Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. Biochem Pharmacol. 1994 Nov 1;48(9):1747-55. [Content Brief]

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