Liver carboxylesterase 1 also known as carboxylesterase 1 (CES1, hCE-1 or CES1A1) is an enzyme that in humans is encoded by the CES1gene. The protein is also historically known as serineesterase 1 (SES1), monocyte esterase and cholesterol esterhydrolase (CEH). Three transcript variants encoding three different isoforms have been found for this gene. The various protein products from isoform a, b and c range in size from 568, 567 and 566 amino acids long, respectively.
Carboxylesterase 1 is a serine esterase and member of a large multigene carboxylesterase family. It is also part of the alpha/beta fold hydrolase family. These enzymes are responsible for the hydrolysis of ester- and amide-bond-containing xenobiotics and drugs such as cocaine and heroin. They also hydrolyze long-chain fatty acid esters and thioesters. As part of phase II metabolism, the resulting carboxylates are then often conjugated by other enzymes to increase solubility and eventually excreted.
This enzyme is known to hydrolyze aromatic and aliphatic esters and can manage cellular cholesterol esterification levels. It may also play a role in detoxification in the lung and/or protection of the central nervous system from ester or amide compounds.
CES1 can activate or deactivate various drugs. CES1 is responsible for the activation of many prodrugs such as angiotensin-converting enzyme (ACE) inhibitors, oseltamivir, and dabigatran.  Genetic variants of CES1 can significantly affect both pharmaocokinetics and pharmacodynamics of drugs metabolized by CES1, such as methylphenidate and clopidogrel. The ability of CES1 to metabolize heroin and cocaine among other drugs has suggested a therapeutic role for the enzyme.
^Zhu HJ, Appel DI, Johnson JA, Chavin KD, Markowitz JS. (Jan 2009). "Role of carboxylesterase 1 and impact of natural genetic variants on the hydrolysis of trandolapril". Biochem Pharmacol77 (7): 1266–72. doi:10.1016/j.bcp.2008.12.017. PMID19185566.
^Thomsen R, Rasmussen HB, Linnet K; INDICES Consortium. (Jan 2014). "In vitro drug metabolism by human carboxylesterase 1: focus on angiotensin-converting enzyme inhibitors". Drug Metab Dispos42 (1): 126–33. doi:10.1124/dmd.113.053512. PMID24141856.
^Zhu HJ, Markowitz JS. (Feb 2009). "Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants". Drug Metab Dispos37 (2): 264–7. doi:10.1124/dmd.108.024943. PMID19022936.
^Paré G, Eriksson N, Lehr T, Connolly S, Eikelboom J, Ezekowitz MD, Axelsson T, Haertter S, Oldgren J, Reilly P, Siegbahn A, Syvanen AC, Wadelius C, Wadelius M, Zimdahl-Gelling H, Yusuf S, Wallentin L. (Apr 2013). "Genetic determinants of dabigatran plasma levels and their relation to bleeding". Circulation127 (13): 1404–12. doi:10.1124/dmd.108.024943. PMID23467860.
Munger JS, Shi GP, Mark EA et al. (1991). "A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases.". J. Biol. Chem.266 (28): 18832–8. PMID1918003.
Becker A, Böttcher A, Lackner KJ et al. (1994). "Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase.". Arterioscler. Thromb.14 (8): 1346–55. doi:10.1161/01.atv.14.8.1346. PMID8049197.
Kroetz DL, McBride OW, Gonzalez FJ (1993). "Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms.". Biochemistry32 (43): 11606–17. doi:10.1021/bi00094a018. PMID8218228.
Shibata F, Takagi Y, Kitajima M et al. (1993). "Molecular cloning and characterization of a human carboxylesterase gene.". Genomics17 (1): 76–82. doi:10.1006/geno.1993.1285. PMID8406473.
Langmann T, Becker A, Aslanidis C et al. (1997). "Structural organization and characterization of the promoter region of a human carboxylesterase gene.". Biochim. Biophys. Acta1350 (1): 65–74. doi:10.1016/S0167-4781(96)00142-X. PMID9003459.
Brzezinski MR, Spink BJ, Dean RA et al. (1997). "Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs.". Drug Metab. Dispos.25 (9): 1089–96. PMID9311626.
Yan B, Matoney L, Yang D (1999). "Human carboxylesterases in term placentae: enzymatic characterization, molecular cloning and evidence for the existence of multiple forms.". Placenta20 (7): 599–607. doi:10.1053/plac.1999.0407. PMID10452915.
Islam MR, Waheed A, Shah GN et al. (1999). "Human egasyn binds beta-glucuronidase but neither the esterase active site of egasyn nor the C terminus of beta-glucuronidase is involved in their interaction.". Arch. Biochem. Biophys.372 (1): 53–61. doi:10.1006/abbi.1999.1449. PMID10562416.
Ghosh S (2001). "Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA.". Physiol. Genomics2 (1): 1–8. PMID11015575.
Ghosh S, Natarajan R (2001). "Cloning of the human cholesteryl ester hydrolase promoter: identification of functional peroxisomal proliferator-activated receptor responsive elements.". Biochem. Biophys. Res. Commun.284 (4): 1065–70. doi:10.1006/bbrc.2001.5078. PMID11409902.
Alam M, Ho S, Vance DE, Lehner R (2002). "Heterologous expression, purification, and characterization of human triacylglycerol hydrolase.". Protein Expr. Purif.24 (1): 33–42. doi:10.1006/prep.2001.1553. PMID11812220.
Satoh T, Taylor P, Bosron WF et al. (2002). "Current progress on esterases: from molecular structure to function.". Drug Metab. Dispos.30 (5): 488–93. doi:10.1124/dmd.30.5.488. PMID11950776.
Alam M, Vance DE, Lehner R (2002). "Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site.". Biochemistry41 (21): 6679–87. doi:10.1021/bi0255625. PMID12022871.
Bencharit S, Morton CL, Xue Y et al. (2003). "Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme.". Nat. Struct. Biol.10 (5): 349–56. doi:10.1038/nsb919. PMID12679808.
Zhu HJ, Brinda B, Froehlich TE, Markowitz JS. (2012). "A discriminative analytical method for detection of CES1A1 and CES1A2/CES1A3 genetic variants.". Pharmacogenet Genomics.22 (3): 215–8. doi:10.1097/FPC.0b013e32834f03eb. PMID22237548.