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Gene Review

CES1  -  carboxylesterase 1

Homo sapiens

Synonyms: ACAT, Acyl-coenzyme A:cholesterol acyltransferase, Brain carboxylesterase hBr1, CE-1, CEH, ...
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Disease relevance of CES1

  • Expression of human TGH in Escherichia coli yields a protein without enzymatic activity, which suggests that posttranslational processing is necessary for the catalytic activity [1].
  • Expression of hTGH with its native signal sequence and a C-terminal 6xHis-tag in Sf9 cells using the baculovirus expression system yielded active enzyme [2].
  • The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study [3].
  • In contrast, Phe-OMe toxicity for myeloid cells was found to correlate with serine esterase-mediated intracellular trapping of high concentrations of the free amino acid Phe [4].
  • A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically reactive with antibody inhibiting syncytia induced by HIV-1. Purification and characterization [5].

High impact information on CES1


Chemical compound and disease context of CES1


Biological context of CES1

  • Relative CES1 and CES2 expression levels were determined by reverse transcription of the respective mRNAs, followed by polymerase chain reaction amplification [14].
  • Human carboxylesterases 1 and 2 (CES1 and CES2) catalyze the hydrolysis of many exogenous compounds [15].
  • We resequenced CES1 and CES2 in multiple populations (n = 120) to identify single-nucleotide polymorphisms and confirmed the novel SNPs in healthy European and African individuals (n = 190) [15].
  • 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 [16].
  • Their coding sequences showed high homology, with only four amino acid differences in the N-terminal region, but our sequencing study of the 5' regions revealed that CES1A1 and CES1A2 had distinctive consensus sequences for transcription factors in the regions, implying differences in transcriptional regulation of the genes [17].

Anatomical context of CES1


Associations of CES1 with chemical compounds


Physical interactions of CES1

  • Pretreatment of neutrophils with serine esterase inhibitors did not abrogate binding capacity of the cells for C1-INH, whereas the binding affinity for C1-INH was lost when the cells were pretreated with trypsin [25].

Regulatory relationships of CES1

  • A serine esterase inhibitor blocked this activity and a recombinant PON1 was devoid of it, raising the possibility that the activity represents platelet-activating factor acetylhydrolase (PAF-AH), an esterase that co-purifies with PON1 from HDL [26].
  • We show evidence that both PAF acetylhydrolase (PAF-AH) and transacetylase activities are inhibited to the same extent by serine esterase inhibitors, are resistant to heat treatment, and exhibit identical distributions in lipoprotein classes and in LDL subfractions [27].
  • The activity of leukocyte migration inhibitory factor (LIF) obtained from Sephadex-G-100-chromatographed supernatants of concanavalin-A-stimulated human lymphocytes was suppressed by two synthetic serine esterase and serine protease inhibitors (di-isopropylfluorophosphate (DFP) and phenylmethylfulfonyl fluoride (PMSF)) [28].

Other interactions of CES1


Analytical, diagnostic and therapeutic context of CES1

  • The 1941-bp cDNA differs by only a few bases from two previously reported cDNAs for human liver carboxylesterase, allowing the anti-human carboxylesterase antiserum to be used for immunoprecipitation of human egasyn [16].
  • When these cells were incubated in lipoprotein-deficient serum for 18 hours, the mRNA for ACAT/carboxylesterase was almost not detectable on Northern blots, whereas after incubation with acetylated low-density lipoproteins, a strong hybridization signal was obtained [33].
  • The sensitive technique of RT-PCR was used to identify cholesteryl ester hydrolase (CEH) expressed in human macrophages [34].
  • In the present study, to investigate the transcriptional regulation of the promoter region of the CES1 and CES2 genes were isolated from mouse, rat and human genomic DNA by PCR amplification [35].
  • We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy [3].


  1. Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site. Alam, M., Vance, D.E., Lehner, R. Biochemistry (2002) [Pubmed]
  2. Heterologous expression, purification, and characterization of human triacylglycerol hydrolase. Alam, M., Ho, S., Vance, D.E., Lehner, R. Protein Expr. Purif. (2002) [Pubmed]
  3. Hepatic cholesterol ester hydrolase in human liver disease. Simon, J.B., Poon, R.W. Gastroenterology (1978) [Pubmed]
  4. Spectrum of toxicities of amino acid methyl esters for myeloid cells is determined by distinct metabolic pathways. Thiele, D.L., Lipsky, P.E. Blood (1992) [Pubmed]
  5. A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically reactive with antibody inhibiting syncytia induced by HIV-1. Purification and characterization. Kido, H., Fukutomi, A., Katunuma, N. J. Biol. Chem. (1990) [Pubmed]
  6. Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Metzstein, M.M., Hengartner, M.O., Tsung, N., Ellis, R.E., Horvitz, H.R. Nature (1996) [Pubmed]
  7. SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Inukai, T., Inoue, A., Kurosawa, H., Goi, K., Shinjyo, T., Ozawa, K., Mao, M., Inaba, T., Look, A.T. Mol. Cell (1999) [Pubmed]
  8. Expression of perforin and serine esterases by human gamma/delta T cells. Koizumi, H., Liu, C.C., Zheng, L.M., Joag, S.V., Bayne, N.K., Holoshitz, J., Young, J.D. J. Exp. Med. (1991) [Pubmed]
  9. Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. Cooper, C.L., Mueller, C., Sinchaisri, T.A., Pirmez, C., Chan, J., Kaplan, G., Young, S.M., Weissman, I.L., Bloom, B.R., Rea, T.H. J. Exp. Med. (1989) [Pubmed]
  10. The effect of acyl CoA: cholesterol acyltransferase inhibition on the uptake, esterification and secretion of cholesterol by the hamster small intestine. Burrier, R.E., Smith, A.A., McGregor, D.G., Hoos, L.M., Zilli, D.L., Davis, H.R. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  11. Metabolism of monoepoxides of methyl linoleate: bioactivation and detoxification. Greene, J.F., Williamson, K.C., Newman, J.W., Morisseau, C., Hammock, B.D. Arch. Biochem. Biophys. (2000) [Pubmed]
  12. Diisopropylfluorophosphate-evoked inhibition of anaphylactic histamine release from human skin: decrease of the inhibition by storing the skin specimens. Yamamoto, S., Greaves, M.W. Acta Derm. Venereol. (1979) [Pubmed]
  13. Inhibition of tryptase TL2 from human T4+ lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. Brinkmann, T., Schäfers, J., Gürtler, L., Kido, H., Niwa, Y., Katunuma, N., Tschesche, H. J. Protein Chem. (1997) [Pubmed]
  14. Design, synthesis, and preliminary evaluation of doxazolidine carbamates as prodrugs activated by carboxylesterases. Burkhart, D.J., Barthel, B.L., Post, G.C., Kalet, B.T., Nafie, J.W., Shoemaker, R.K., Koch, T.H. J. Med. Chem. (2006) [Pubmed]
  15. Pharmacogenomic assessment of carboxylesterases 1 and 2. Marsh, S., Xiao, M., Yu, J., Ahluwalia, R., Minton, M., Freimuth, R.R., Kwok, P.Y., McLeod, H.L. Genomics (2004) [Pubmed]
  16. 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. Islam, M.R., Waheed, A., Shah, G.N., Tomatsu, S., Sly, W.S. Arch. Biochem. Biophys. (1999) [Pubmed]
  17. Human carboxylesterase 1A2 expressed from carboxylesterase 1A1 and 1A2 genes is a potent predictor of CPT-11 cytotoxicity in vitro. Tanimoto, K., Kaneyasu, M., Shimokuni, T., Hiyama, K., Nishiyama, M. Pharmacogenet. Genomics (2007) [Pubmed]
  18. Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy. Vallejo, M., Briz, O., Serrano, M.A., Monte, M.J., Marin, J.J. J. Hepatol. (2006) [Pubmed]
  19. cDNA cloning and characterization of human monocyte/macrophage serine esterase-1. Zschunke, F., Salmassi, A., Kreipe, H., Buck, F., Parwaresch, M.R., Radzun, H.J. Blood (1991) [Pubmed]
  20. A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. Munger, J.S., Shi, G.P., Mark, E.A., Chin, D.T., Gerard, C., Chapman, H.A. J. Biol. Chem. (1991) [Pubmed]
  21. Cloning of the human cholesteryl ester hydrolase promoter: identification of functional peroxisomal proliferator-activated receptor responsive elements. Ghosh, S., Natarajan, R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  22. Nucleoside ester prodrug substrate specificity of liver carboxylesterase. Landowski, C.P., Lorenzi, P.L., Song, X., Amidon, G.L. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  23. A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity. Geshi, E., Kimura, T., Yoshimura, M., Suzuki, H., Koba, S., Sakai, T., Saito, T., Koga, A., Muramatsu, M., Katagiri, T. Hypertens. Res. (2005) [Pubmed]
  24. Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors. Azrak, R.G., Yu, J., Pendyala, L., Smith, P.F., Cao, S., Li, X., Shannon, W.D., Durrani, F.A., McLeod, H.L., Rustum, Y.M. Mol. Cancer Ther. (2005) [Pubmed]
  25. Characterization of C1 inhibitor binding to neutrophils. Chang, N.S., Boackle, R.J., Leu, R.W. Immunology (1991) [Pubmed]
  26. Phospholipase Action of Platelet-activating Factor Acetylhydrolase, but Not Paraoxonase-1, on Long Fatty Acyl Chain Phospholipid Hydroperoxides. Kriska, T., Marathe, G.K., Schmidt, J.C., McIntyre, T.M., Girotti, A.W. J. Biol. Chem. (2007) [Pubmed]
  27. Platelet-activating factor acetylhydrolase and transacetylase activities in human plasma low-density lipoprotein. Tsoukatos, D.C., Liapikos, T.A., Tselepis, A.D., Chapman, M.J., Ninio, E. Biochem. J. (2001) [Pubmed]
  28. Human leukocyte migration inhibitory factor (LIF). I. Effect of synthetic and naturally occurring esterase and protease inhibitors. Bendtzen, K. Scand. J. Immunol. (1977) [Pubmed]
  29. Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. Sun, Z., Murry, D.J., Sanghani, S.P., Davis, W.I., Kedishvili, N.Y., Zou, Q., Hurley, T.D., Bosron, W.F. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  30. Carnosic acid and promotion of monocytic differentiation of HL60-G cells initiated by other agents. Danilenko, M., Wang, X., Studzinski, G.P. J. Natl. Cancer Inst. (2001) [Pubmed]
  31. Receptor modulation and early signal transduction events in cytotoxic T lymphocytes inactivated by sensitive target cells. Hommel-Berrey, G.A., Shenoy, A.M., Brahmi, Z. J. Immunol. (1991) [Pubmed]
  32. Platelet-activating factor acetylhydrolase, and not paraoxonase-1, is the oxidized phospholipid hydrolase of high density lipoprotein particles. Marathe, G.K., Zimmerman, G.A., McIntyre, T.M. J. Biol. Chem. (2003) [Pubmed]
  33. Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase. Becker, A., Böttcher, A., Lackner, K.J., Fehringer, P., Notka, F., Aslanidis, C., Schmitz, G. Arterioscler. Thromb. (1994) [Pubmed]
  34. Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA. Ghosh, S. Physiol. Genomics (2000) [Pubmed]
  35. Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes. Hosokawa, M., Furihata, T., Yaginuma, Y., Yamamoto, N., Koyano, N., Fujii, A., Nagahara, Y., Satoh, T., Chiba, K. Drug Metab. Rev. (2007) [Pubmed]
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