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Gene Review

LCAT  -  lecithin-cholesterol acyltransferase

Homo sapiens

Synonyms: Lecithin-cholesterol acyltransferase, Phosphatidylcholine-sterol acyltransferase, Phospholipid-cholesterol acyltransferase
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Disease relevance of LCAT

  • Forty percent of plasma LCAT-HDL was associated with alpha(2)M; moreover, most of the LCAT in cerebrospinal fluid and in the medium of cultured human hepatoma cell line was associated with alpha(2)M [1].
  • Most, if not all, of the lipoprotein changes observed are explained by the LCAT deficiency that follows IL-2-induced hepatocellular injury and cholestasis [2].
  • Plasma activities of CETP and LCAT were measured in 137 male patients with moderate hypertriglyceridemia (plasma triglycerides [TGs] 200 to 500 mg/dL and LDL cholesterol < 160 mg/dL) [3].
  • Plasma lipoprotein concentrations and post-heparin lipoprotein lipase, hepatic triglyceride lipase (HTGL), and lecithin:cholesterol acyltransferase (LCAT) activities were determined in 10 obese women before and after weight loss [4].
  • High dose i.v. rIL-2 induces severe dyslipidemia with deficiencies of both postheparin lipases and acute LCAT deficiency [2].

Psychiatry related information on LCAT


High impact information on LCAT

  • This apoprotein serves as a cofactor for the plasma lecithin-cholesterol acyltransferase (LCAT) enzyme responsible for the formation of most cholesteryl esters in plasma, and also promotes cholesterol efflux from cells [8].
  • The cholesterol in discoidal HDL is esterified by lecithin:cholesterol acyltransferase (LCAT) in a process that converts the prebeta-migrating disc into an alpha-migrating, spherical HDL [9].
  • LCAT and apoE contents of CETP-D HDL-2 were markedly increased compared with control HDL-2, and increased cholesterol esterification activity resided within the apoE-HDL fraction [10].
  • ApoA-I FCR was inversely associated with HDL cholesterol level (r=-0.851,P<0.01) and hLCAT activity (r=-0.816, P<0.01) [11].
  • To elucidate the mechanisms responsible for this effect, 131I-HDL apoA-I kinetics were assessed in age- and sex-matched groups of rabbits (n=3 each) with high, low, or no hLCAT expression [11].

Chemical compound and disease context of LCAT


Biological context of LCAT

  • Our data indicate that the regions adjacent to Thr123 and Thr347 of LCAT may play an important role in HDL cholesterol esterification, suggesting that these regions may contain a portion of the LCAT binding domain(s) for HDL [17].
  • LCAT activity and LCAT mass in 23 genotypic heterozygotes were approximately half normal and clearly distinct from those of 20 unaffected family members [18].
  • In the homozygous patients no obvious relationship between residual LCAT activity and the clinical phenotype was seen [18].
  • DNA sequence analysis of the proband's LCAT gene revealed two separate C to T transitions resulting in the substitution of Thr123 with Ile and Thr347 with Met [17].
  • To assess the effects of increased plasma levels of LCAT, four lines of transgenic mice were created expressing a Hu LCAT gene driven by either its natural or the mouse albumin enhancer promoter [19].

Anatomical context of LCAT

  • These findings led us to postulate that poor activation of LCAT in interstitial fluid may result from a change in conformation in apoA-I [20].
  • The 1550 base LCAT mRNA can be detected in liver and HepG2 (hepatocyte) cells, but not in small intestine, spleen, pancreas, placenta or adrenal tissue [21].
  • Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity [22].
  • To determine whether alpha-LpA-I generated by fibroblasts is a good substrate for LCAT, isolated alpha-LpA-I as well as reconstituted HDL [r(HDL)] was reacted with LCAT [23].
  • Postprandial chylomicrons: potent vehicles for transporting cholesterol from endogenous LDL+HDL and cell membranes to the liver via LCAT and CETP [24].

Associations of LCAT with chemical compounds


Physical interactions of LCAT


Regulatory relationships of LCAT

  • Furthermore, the finding supports the possibility that the LRP receptor can act in vivo to mediate clearance of the LCAT-alpha(2)M complex and may significantly influence the bioavailability of LCAT [1].
  • Using transfected HepG2 cells, results indicate that treatment with IL-6 induced a 2.5-fold activation of full-length LCAT promoter activity [32].
  • The results suggest that Hpt inhibits the reverse transport of cholesterol by preventing ApoA1 stimulation of the LCAT activity [33].
  • Our experiments demonstrate that LCAT promotes HDL3/HDL2 interconversion in native serum irrespective of the presence or absence of triglyceride-rich lipoproteins and lipoprotein lipase [34].
  • Apo-E was found to be 18% as effective as apo-A-I in activating purified human lecithin cholesterol acyltransferase [35].

Other interactions of LCAT

  • Evidence for linkage was observed at the MnSOD (P=.02), CETP/LCAT (P=.03), and apolipoprotein AI-CIII-AIV loci (P=.005) but not at the LDLR locus [36].
  • These data show that carriers of an apoA-I mutation exhibit the most pronounced accelerated atherosclerosis compared with those carrying mutations in ABCA1 and LCAT [37].
  • By stepwise regression analysis CETP appeared to contribute 15.2% and LCAT 9.8% to variation in HDL-cholesterol levels [3].
  • In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns [22].
  • ApoA-I enters the plasma as a component of discoidal particles, which are remodeled into spherical (A-I)HDL by LCAT [38].

Analytical, diagnostic and therapeutic context of LCAT

  • The mass of LCAT secreted, determined by immunoassay, did not differ in the native and mutant species [25].
  • Electron microscopy of the proteoliposome LCAT substrate generated by WT and mutant apoA-I forms showed that the carboxyl-terminal deletion mutants which displayed aberrant binding to HDL also displayed reduced ability to convert the spherical lecithin-cholesterol vesicles into discs compared with WT [27].
  • Plasma lecithin-cholesterol acyltransferase (LCAT) activity, lipoprotein composition, and lipoprotein concentrations were measured in 21 children with kwashiorkor before (day 1), during (day 10), and after treatment (day 30) [39].
  • Moreover, LCAT's antiatherogenic effect requires only a single functional LDLr allele, identifying LCAT as an attractive gene therapy candidate for the majority of dyslipoproteinemic patients [40].
  • Since recent studies have shown that a tryptophan residue in the putative interfacial domain (Trp(61)) is critical for the activity, we determined the possible role of this residue in the oxidative susceptibility and substrate specificity of LCAT by site-directed mutagenesis [41].


  1. Interaction of lecithin:cholesterol acyltransferase (LCAT).alpha 2-macroglobulin complex with low density lipoprotein receptor-related protein (LRP). Evidence for an alpha 2-macroglobulin/LRP receptor-mediated system participating in LCAT clearance. Krimbou, L., Marcil, M., Davignon, J., Genest, J. J. Biol. Chem. (2001) [Pubmed]
  2. Acute dyslipoproteinemia induced by interleukin-2: lecithin:cholesteryl acyltransferase, lipoprotein lipase, and hepatic lipase deficiencies. Kwong, L.K., Ridinger, D.N., Bandhauer, M., Ward, J.H., Samlowski, W.E., Iverius, P.H., Pritchard, H., Wilson, D.E. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  3. Determinants of plasma HDL-cholesterol in hypertriglyceridemic patients. Role of cholesterol-ester transfer protein and lecithin cholesteryl acyl transferase. Tato, F., Vega, G.L., Grundy, S.M. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  4. Plasma lipoproteins and lipase and lecithin:cholesterol acyltransferase activities in obese subjects before and after weight reduction. Weisweiler, P. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  5. Alterations of lipolytic enzymes and high-density lipoprotein subfractions induced by physical activity in type 2 diabetes mellitus. Lehmann, R., Engler, H., Honegger, R., Riesen, W., Spinas, G.A. Eur. J. Clin. Invest. (2001) [Pubmed]
  6. Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition. Hendriks, H.F., Veenstra, J., van Tol, A., Groener, J.E., Schaafsma, G. Alcohol Alcohol. (1998) [Pubmed]
  7. Cholesterol turnover and risk factors for the development of coronary heart disease. Dobiásová, M., Vondra, K. Czechoslovak medicine. (1982) [Pubmed]
  8. An inherited polymorphism in the human apolipoprotein A-I gene locus related to the development of atherosclerosis. Karathanasis, S.K., Norum, R.A., Zannis, V.I., Breslow, J.L. Nature (1983) [Pubmed]
  9. Hugh sinclair lecture: the regulation and remodelling of HDL by plasma factors. Barter, P.J. Atherosclerosis. Supplements. (2002) [Pubmed]
  10. HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway. Matsuura, F., Wang, N., Chen, W., Jiang, X.C., Tall, A.R. J. Clin. Invest. (2006) [Pubmed]
  11. Hyperalphalipoproteinemia in human lecithin cholesterol acyltransferase transgenic rabbits. In vivo apolipoprotein A-I catabolism is delayed in a gene dose-dependent manner. Brousseau, M.E., Santamarina-Fojo, S., Zech, L.A., Bérard, A.M., Vaisman, B.L., Meyn, S.M., Powell, D., Brewer, H.B., Hoeg, J.M. J. Clin. Invest. (1996) [Pubmed]
  12. Secretion of active human lecithin-cholesterol acyltransferase by insect cells infected with a recombinant baculovirus. Chawla, D., Owen, J.S. Biochem. J. (1995) [Pubmed]
  13. Contribution of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase to HDL size distribution. Huesca-Gómez, C., Carreón-Torres, E., Nepomuceno-Mejía, T., Sánchez-Solorio, M., Galicia-Hidalgo, M., Mejía, A.M., Montaño, L.F., Franco, M., Posadas-Romero, C., Pérez-Méndez, O. Endocr. Res. (2004) [Pubmed]
  14. Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia. Napoli, C., Leccese, M., Palumbo, G., de Nigris, F., Chiariello, P., Zuliani, P., Somma, P., Di Loreto, M., De Matteis, C., Cacciatore, F., Abete, P., Liguori, A., Chiariello, M., D'Armiento, F.P. Coron. Artery Dis. (1998) [Pubmed]
  15. Effects of probucol and pravastatin on plasma lipids, activities of postheparin lipoprotein lipase, and lecithin cholesterol acyltransferase and apo A-I containing lipoproteins with and without apo A-II in patients with moderate hypercholesterolemia. Kagami, A., Ishikawa, T., Tada, N., Sakamoto, T., Mochizuki, K., Nagano, M., Moriguchi, E.H., Manabe, M. Clin. Biochem. (1993) [Pubmed]
  16. Effects of high dose progestin on serum lipids and lipid metabolizing enzymes in patients with endometrial cancer. Lehtonen, A., Grönroos, M., Marniemi, J., Peltonen, P., Mäntylä, M., Niskanen, J., Rautio, A., Hietanen, E. Horm. Metab. Res. (1985) [Pubmed]
  17. Two different allelic mutations in the lecithin-cholesterol acyltransferase gene associated with the fish eye syndrome. Lecithin-cholesterol acyltransferase (Thr123----Ile) and lecithin-cholesterol acyltransferase (Thr347----Met). Klein, H.G., Lohse, P., Pritchard, P.H., Bojanovski, D., Schmidt, H., Brewer, H.B. J. Clin. Invest. (1992) [Pubmed]
  18. Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease. Funke, H., von Eckardstein, A., Pritchard, P.H., Hornby, A.E., Wiebusch, H., Motti, C., Hayden, M.R., Dachet, C., Jacotot, B., Gerdes, U. J. Clin. Invest. (1993) [Pubmed]
  19. Expression of human lecithin-cholesterol acyltransferase in transgenic mice. Effect of human apolipoprotein AI and human apolipoprotein all on plasma lipoprotein cholesterol metabolism. Francone, O.L., Gong, E.L., Ng, D.S., Fielding, C.J., Rubin, E.M. J. Clin. Invest. (1995) [Pubmed]
  20. Altered epitope expression of human interstitial fluid apolipoprotein A-I reduces its ability to activate lecithin cholesterol acyl transferase. Wong, L., Curtiss, L.K., Huang, J., Mann, C.J., Maldonado, B., Roheim, P.S. J. Clin. Invest. (1992) [Pubmed]
  21. Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression. McLean, J., Wion, K., Drayna, D., Fielding, C., Lawn, R. Nucleic Acids Res. (1986) [Pubmed]
  22. Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels. Miettinen, H.E., Gylling, H., Tenhunen, J., Virtamo, J., Jauhiainen, M., Huttunen, J.K., Kantola, I., Miettinen, T.A., Kontula, K. Arterioscler. Thromb. Vasc. Biol. (1998) [Pubmed]
  23. Biogenesis and speciation of nascent apoA-I-containing particles in various cell lines. Krimbou, L., Hajj Hassan, H., Blain, S., Rashid, S., Denis, M., Marcil, M., Genest, J. J. Lipid Res. (2005) [Pubmed]
  24. Postprandial chylomicrons: potent vehicles for transporting cholesterol from endogenous LDL+HDL and cell membranes to the liver via LCAT and CETP. Chung, B.H., Liang, P., Doran, S., Cho, B.H., Franklin, F. J. Lipid Res. (2004) [Pubmed]
  25. Effects of site-directed mutagenesis at residues cysteine-31 and cysteine-184 on lecithin-cholesterol acyltransferase activity. Francone, O.L., Fielding, C.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  26. Sphingomyelin inhibits the lecithin-cholesterol acyltransferase reaction with reconstituted high density lipoproteins by decreasing enzyme binding. Bolin, D.J., Jonas, A. J. Biol. Chem. (1996) [Pubmed]
  27. Site-directed mutagenesis and structure-function analysis of the human apolipoprotein A-I. Relation between lecithin-cholesterol acyltransferase activation and lipid binding. Minnich, A., Collet, X., Roghani, A., Cladaras, C., Hamilton, R.L., Fielding, C.J., Zannis, V.I. J. Biol. Chem. (1992) [Pubmed]
  28. Structure of apolipoprotein A-I in three homogeneous, reconstituted high density lipoprotein particles. Wald, J.H., Krul, E.S., Jonas, A. J. Biol. Chem. (1990) [Pubmed]
  29. A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response. Kumon, Y., Nakauchi, Y., Kidawara, K., Fukushima, M., Kobayashi, S., Ikeda, Y., Suehiro, T., Hashimoto, K., Sipe, J.D. Scand. J. Immunol. (1998) [Pubmed]
  30. Activation of lecithin-cholesterol acyltransferase by apolipoprotein D: comparison of proteoliposomes containing apolipoprotein D, A-I or C-I. Steyrer, E., Kostner, G.M. Biochim. Biophys. Acta (1988) [Pubmed]
  31. Influence of serum amyloid A on cholesterol esterification in human plasma. Steinmetz, A., Hocke, G., Saïle, R., Puchois, P., Fruchart, J.C. Biochim. Biophys. Acta (1989) [Pubmed]
  32. Identification of an IL-6 response element in the human LCAT promoter. Feister, H.A., Auerbach, B.J., Cole, L.A., Krause, B.R., Karathanasis, S.K. J. Lipid Res. (2002) [Pubmed]
  33. Haptoglobin inhibits lecithin-cholesterol acyltransferase in human ovarian follicular fluid. Balestrieri, M., Cigliano, L., Simone, M.L., Dale, B., Abrescia, P. Mol. Reprod. Dev. (2001) [Pubmed]
  34. The role of lecithin: cholesterol acyltransferase in high density lipoprotein3/high density lipoprotein2 interconversion. Schmitz, G., Assmann, G., Melnik, B. Clin. Chim. Acta (1982) [Pubmed]
  35. Activation of lecithin cholesterol acyltransferase by human apolipoprotein E in discoidal complexes with lipids. Zorich, N., Jonas, A., Pownall, H.J. J. Biol. Chem. (1985) [Pubmed]
  36. Families with familial combined hyperlipidemia and families enriched for coronary artery disease share genetic determinants for the atherogenic lipoprotein phenotype. Allayee, H., Aouizerat, B.E., Cantor, R.M., Dallinga-Thie, G.M., Krauss, R.M., Lanning, C.D., Rotter, J.I., Lusis, A.J., de Bruin, T.W. Am. J. Hum. Genet. (1998) [Pubmed]
  37. Inherited disorders of HDL metabolism and atherosclerosis. Hovingh, G.K., de Groot, E., van der Steeg, W., Boekholdt, S.M., Hutten, B.A., Kuivenhoven, J.A., Kastelein, J.J. Curr. Opin. Lipidol. (2005) [Pubmed]
  38. Formation of high density lipoproteins containing both apolipoprotein A-I and A-II in the rabbit. Hime, N.J., Drew, K.J., Wee, K., Barter, P.J., Rye, K.A. J. Lipid Res. (2006) [Pubmed]
  39. Plasma lecithin-cholesterol acyltransferase activity and plasma lipoprotein composition and concentrations in kwashiorkor. Dhansay, M.A., Benadé, A.J., Donald, P.R. Am. J. Clin. Nutr. (1991) [Pubmed]
  40. LCAT modulates atherogenic plasma lipoproteins and the extent of atherosclerosis only in the presence of normal LDL receptors in transgenic rabbits. Brousseau, M.E., Kauffman, R.D., Herderick, E.E., Demosky, S.J., Evans, W., Marcovina, S., Santamarina-Fojo, S., Brewer, H.B., Hoeg, J.M. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  41. Role of the interfacial binding domain in the oxidative susceptibility of lecithin:cholesterol acyltransferase. Wang, K., Subbaiah, P.V. Biochem. J. (2002) [Pubmed]
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