phosphatidylcholine sterol o acyltransferase

Summary

Summary: An enzyme secreted from the liver into the plasma of many mammalian species. It catalyzes the esterification of the hydroxyl group of lipoprotein cholesterol by the transfer of a fatty acid from the C-2 position of lecithin. In familial lecithin:cholesterol acyltransferase deficiency disease, the absence of the enzyme results in an excess of unesterified cholesterol in plasma.

Top Publications

  1. Jonas A. Lecithin cholesterol acyltransferase. Biochim Biophys Acta. 2000;1529:245-56 pubmed
    ..Finally, overexpression of the human LCAT gene in mice and rabbits has been used to examine the physiologic role of LCAT in vivo and its protective effect against diet induced atherosclerosis. ..
  2. Sviridov D, Hoang A, Sawyer W, Fidge N. Identification of a sequence of apolipoprotein A-I associated with the activation of Lecithin:Cholesterol acyltransferase. J Biol Chem. 2000;275:19707-12 pubmed
  3. Guerin M, Dachet C, Goulinet S, Chevet D, Dolphin P, Chapman M, et al. Familial lecithin:cholesterol acyltransferase deficiency: molecular analysis of a compound heterozygote: LCAT (Arg147 --> Trp) and LCAT (Tyr171 --> Stop). Atherosclerosis. 1997;131:85-95 pubmed
    ..In summary, we have identified an LCAT deficient patient corresponding to a compound heterozygote for the Arg147 --> Trp mutation and a new molecular defect involving a Tyr171 --> Stop mutation in the LCAT gene. ..
  4. Datta G, Chaddha M, Hama S, Navab M, Fogelman A, Garber D, et al. Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide. J Lipid Res. 2001;42:1096-104 pubmed
    ..These studies provide a rationale for the design of small apoA-I-mimetics with increased potency for atherosclerosis inhibition. ..
  5. Kypreos K, Zannis V. Pathway of biogenesis of apolipoprotein E-containing HDL in vivo with the participation of ABCA1 and LCAT. Biochem J. 2007;403:359-67 pubmed
    ..HDL particles generated by this pathway may account at least for some of the atheroprotective functions of apoE...
  6. Funke H, von Eckardstein A, Pritchard P, Albers J, Kastelein J, Droste C, et al. A molecular defect causing fish eye disease: an amino acid exchange in lecithin-cholesterol acyltransferase (LCAT) leads to the selective loss of alpha-LCAT activity. Proc Natl Acad Sci U S A. 1991;88:4855-9 pubmed
    ..The homozygous presence of this mutation in two phenotypically homozygous members of an unrelated Dutch family with fish eye disease further supports this finding. ..
  7. Brousseau M, Kauffman R, Herderick E, Demosky S, Evans W, Marcovina S, et al. LCAT modulates atherogenic plasma lipoproteins and the extent of atherosclerosis only in the presence of normal LDL receptors in transgenic rabbits. Arterioscler Thromb Vasc Biol. 2000;20:450-8 pubmed
    ..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. ..
  8. Salvatore A, Cigliano L, Bucci E, Corpillo D, Velasco S, Carlucci A, et al. Haptoglobin binding to apolipoprotein A-I prevents damage from hydroxyl radicals on its stimulatory activity of the enzyme lecithin-cholesterol acyl-transferase. Biochemistry. 2007;46:11158-68 pubmed
    ..Therefore haptoglobin, when circulating at enhanced levels with free Hb during the acute phase of inflammation, might protect ApoA-I structure and function against hydroxyl radicals. ..
  9. Zannis V, Chroni A, Krieger M. Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. J Mol Med (Berl). 2006;84:276-94 pubmed

More Information

Publications62

  1. Rader D, Ikewaki K, Duverger N, Schmidt H, Pritchard H, Frohlich J, et al. Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease. J Clin Invest. 1994;93:321-30 pubmed
  2. Spagnuolo M, Cigliano L, D Andrea L, Pedone C, Abrescia P. Assignment of the binding site for haptoglobin on apolipoprotein A-I. J Biol Chem. 2005;280:1193-8 pubmed
    ..Synthetic peptides, able to displace Hpt from ApoA-I without altering its property of binding hemoglobin, might be used for treatment of diseases associated with defective LCAT function. ..
  3. Ng D. Insight into the role of LCAT from mouse models. Rev Endocr Metab Disord. 2004;5:311-8 pubmed
  4. Subbaiah P, Liu M. Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids. Biochim Biophys Acta. 1996;1301:115-26 pubmed
  5. Davit Spraul A, Therond P, Leroy A, Palmade Rieunier F, Rousset C, Moatti N, et al. Inhibition of lecithin cholesterol acyltransferase by phosphatidylcholine hydroperoxides. FEBS Lett. 1999;447:106-10 pubmed
  6. Li L, Naples M, Song H, Yuan R, Ye F, Shafi S, et al. LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling. Am J Physiol Endocrinol Metab. 2007;293:E587-94 pubmed
  7. Zhu X, Xu H, Hou R, Liu H, Xiao B, Yang X, et al. [Lecithin-cholesterol acyltransferase gene 608C/T polymorphism associated with atherosclerotic cerebral infarction]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23:419-22 pubmed
    ..05). The LCAT 608C/T polymorphism is possibly a predisposing factor in ACI happening of Chinese Han population. T allele frequency is possibly concerned with the metabolism of HDL-C. ..
  8. Goto A, Sasai K, Suzuki S, Fukutomi T, Ito S, Matsushita T, et al. Plasma concentrations of LPL and LCAT are in putative association with females and alcohol use which are independent negative risk factors for coronary atherosclerosis among Japanese. Clin Chim Acta. 2003;329:69-76 pubmed
  9. Slominskii P, Metel skaia V, Miloserdova O, Perova N, Limborskaia S. [The possible role of genetic factors in the cholesterol high density lipoprotein level in the Moscow population]. Genetika. 2000;36:1401-5 pubmed
    ..Thus, the given panel of proteins connected with the metabolism of blood plasma lipids has no effect on the blood HDL-C concentration in Russian males from the Moscow population. ..
  10. Holvoet P, De Geest B, Van Linthout S, Lox M, Danloy S, Raes K, et al. The Arg123-Tyr166 central domain of human ApoAI is critical for lecithin:cholesterol acyltransferase-induced hyperalphalipoproteinemia and HDL remodeling in transgenic mice. Arterioscler Thromb Vasc Biol. 2000;20:459-66 pubmed
    ..It is, however, critical for LCAT-induced hyperalphalipoproteinemia and HDL remodeling independent of the lipid-binding properties of apoAI. ..
  11. Labeur C, Lins L, Vanloo B, Baert J, Brasseur R, Rosseneu M. Design of a new class of amphipathic helical peptides for the plasma apolipoproteins that promote cellular cholesterol efflux but do not activate LCAT. Arterioscler Thromb Vasc Biol. 1997;17:580-8 pubmed
    ..These parameters do not affect the capacity of the peptide/phospholipid complexes to promote cellular cholesterol efflux. ..
  12. Hill J, O K, Wang X, Pritchard P. Lecithin:cholesterol acyltransferase deficiency: identification of a causative gene mutation and a co-inherited protein polymorphism. Biochim Biophys Acta. 1993;1181:321-3 pubmed
    ..We demonstrate that the Ala-93-->Thr mutation is responsible for the biochemical defect while the Arg-158-->Cys mutation is a co-inherited natural polymorphism of LCAT which results in normal enzyme function. ..
  13. Shrestha S, Freake H, McGrane M, Volek J, Fernandez M. A combination of psyllium and plant sterols alters lipoprotein metabolism in hypercholesterolemic subjects by modifying the intravascular processing of lipoproteins and increasing LDL uptake. J Nutr. 2007;137:1165-70 pubmed
    ..03). These results indicate that the hypocholesterolemic action of PSY and PS can be explained in part by modifications in the intravascular processing of lipoproteins and by increases in LDL receptor-mediated uptake. ..
  14. Harangi M, Mirdamadi H, Seres I, Sztanek F, Molnar M, Kassai A, et al. Atorvastatin effect on the distribution of high-density lipoprotein subfractions and human paraoxonase activity. Transl Res. 2009;153:190-8 pubmed publisher
    ..Atorvastatin alters the HDL subfractions, which may improve its antiatherogenic effect via enhancement of the PON1 activity. ..
  15. Liang K, Vaziri N. HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LCAT, ACAT, LDL receptor, and SRB-1 in hereditary analbuminemia. Kidney Int. 2003;64:192-8 pubmed
    ..Unlike nephrotic syndrome, which causes severe LDL receptor, HDL receptor, and LCAT deficiencies, hereditary analbuminemia does not affect these proteins. ..
  16. Agren J, Kurvinen J, Kuksis A. Isolation of very low density lipoprotein phospholipids enriched in ethanolamine phospholipids from rats injected with Triton WR 1339. Biochim Biophys Acta. 2005;1734:34-43 pubmed
    ..The comparison of the molecular species composition of VLDL and liver phospholipids suggests a selective secretion of PtdEtn and sphingomyelin molecular species during VLDL secretion. ..
  17. Boutboul S, Bourcier T, Chibane S, Heron E, Borderie V, Abitbol M, et al. Gene symbol: LCAT. Disease: Fish eye disease. Hum Genet. 2004;115:533 pubmed
  18. Warden C, Langner C, Gordon J, Taylor B, McLean J, Lusis A. Tissue-specific expression, developmental regulation, and chromosomal mapping of the lecithin: cholesterol acyltransferase gene. Evidence for expression in brain and testes as well as liver. J Biol Chem. 1989;264:21573-81 pubmed
    ..Mapping of the LCAT gene (Lcat) to mouse Chromosome 8 within 2 centimorgans of the Es-2 locus indicates that it does not correspond to any previously mapped loci affecting high density lipoprotein phenotypes in the mouse. ..
  19. Cohen J, Kiss R, Pertsemlidis A, Marcel Y, McPherson R, Hobbs H. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004;305:869-72 pubmed
    ..Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population...
  20. Schaefer E, Santos R, Asztalos B. Marked HDL deficiency and premature coronary heart disease. Curr Opin Lipidol. 2010;21:289-97 pubmed publisher
    ..Our purpose is to review recent publications in the area of marked human HDL deficiency, HDL particles, coronary heart disease (CHD), amyloidosis, the immune response, and kidney disease...
  21. Aranda P, Valdivielso P, Pisciotta L, Garcia I, Garcã A Arias C, Bertolini S, et al. Therapeutic management of a new case of LCAT deficiency with a multifactorial long-term approach based on high doses of angiotensin II receptor blockers (ARBs). Clin Nephrol. 2008;69:213-8 pubmed
  22. Angell R, Mitsuhashi Y, Bigley K, Bauer J. Plasma LCAT activity and lipid subfraction composition in obese beagles undergoing weight loss. Lipids. 2009;44:415-24 pubmed publisher
    ..Both plasma PL and EC fatty acid profiles were similar with both acylglycerol types and EC fatty acids reflected linoleic acid specificity with minimal diet or time effects. ..
  23. Vaziri N, Liang K. Effects of HMG-CoA reductase inhibition on hepatic expression of key cholesterol-regulatory enzymes and receptors in nephrotic syndrome. Am J Nephrol. 2004;24:606-13 pubmed
    ..HMG-CoA reductase inhibition improved hepatic LDL and HDL receptor deficiencies, and ameliorated the associated hyperlipidemia in the nephrotic rats. ..
  24. Aizawa K, Inakuma T. Dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), alters plasma high-density lipoprotein-cholesterol levels and hepatic gene expression in rats. Br J Nutr. 2009;102:1760-6 pubmed publisher
    ..These results suggest that capsanthin had an HDL-cholesterol-raising effect on plasma, and the potential to increase cholesterol efflux to HDL particles by increasing apoA5 levels and/or enhancement of LCAT activity. ..
  25. Höckerstedt A, Jauhiainen M, Tikkanen M. Lecithin/cholesterol acyltransferase induces estradiol esterification in high-density lipoprotein, increasing its antioxidant potential. J Clin Endocrinol Metab. 2004;89:5088-93 pubmed
    ..Elucidation of the possible in vivo role of HDL-associated estrogen esters requires further critical studies including experiments with physiological hormone concentrations. ..
  26. Miida T, Zhang B, Obayashi K, Seino U, Zhu Y, Ito T, et al. T13M mutation of lecithin-cholesterol acyltransferase gene causes fish-eye disease. Clin Chim Acta. 2004;343:201-8 pubmed
    ..In the immunoblot against LCAT, the small alpha-migrating HDL from the proband had much less LCAT in this patient than in controls. T13M mutation of LCAT gene causes FED. ..
  27. Chung B, Doran S, Liang P, Osterlund L, Cho B, Oster R, et al. Alcohol-mediated enhancement of postprandial lipemia: a contributing factor to an increase in plasma HDL and a decrease in risk of cardiovascular disease. Am J Clin Nutr. 2003;78:391-9 pubmed
  28. Duverger N, Murry Brelier A, Latta M, Reboul S, Castro G, Mayaux J, et al. Functional characterization of human recombinant apolipoprotein AIV produced in Escherichia coli. Eur J Biochem. 1991;201:373-83 pubmed
    ..It is concluded that the recombinant protein is functionally identical to the plasmatic apoAIV and may therefore be very useful in helping to elucidate the physiological role of apoAIV. ..
  29. Webb N, de Beer M, Asztalos B, Whitaker N, van der Westhuyzen D, de Beer F. Remodeling of HDL remnants generated by scavenger receptor class B type I. J Lipid Res. 2004;45:1666-73 pubmed
    ..We conclude that HDL remnants, generated by SR-BI, are converted to larger particles by rapidly reassociating with existing HDL particles in an enzyme-independent manner. ..
  30. Calabresi L, Baldassarre D, Castelnuovo S, Conca P, Bocchi L, Candini C, et al. Functional lecithin: cholesterol acyltransferase is not required for efficient atheroprotection in humans. Circulation. 2009;120:628-35 pubmed publisher
    ..This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk. ..
  31. Amar M, Shamburek R, Vaisman B, Knapper C, Foger B, Hoyt R, et al. Adenoviral expression of human lecithin-cholesterol acyltransferase in nonhuman primates leads to an antiatherogenic lipoprotein phenotype by increasing high-density lipoprotein and lowering low-density lipoprotein. Metabolism. 2009;58:568-75 pubmed publisher
    ..05). In summary, overexpression of LCAT in nonhuman primates leads to an antiatherogenic lipoprotein profile by increasing HDL cholesterol and lowering ApoB, thus making LCAT a potential drug target for reducing atherosclerosis. ..
  32. Dobiasova M, Frohlich J. Advances in understanding of the role of lecithin cholesterol acyltransferase (LCAT) in cholesterol transport. Clin Chim Acta. 1999;286:257-71 pubmed
    ..Thus, the plasma HDL, specifically the larger (HDL2b) particles, direct the efflux of most of (LCAT produced) CE to its specific catabolic sites rather than to potentially atherogenic VLDLs and back to LDLs. ..
  33. Höckerstedt A, Jauhiainen M, Tikkanen M. Estradiol fatty acid esterification is increased in high density lipoprotein subclass 3 isolated from hypertriglyceridemic subjects. Atherosclerosis. 2006;185:264-70 pubmed
    ..Thus, HDL composition regulates LCAT-facilitated E2 esterification but the in vivo role of this finding can be verified only in experiments using physiological hormone concentrations. ..
  34. Toth P. Reverse cholesterol transport: high-density lipoprotein's magnificent mile. Curr Atheroscler Rep. 2003;5:386-93 pubmed
  35. Taki M, Teramoto T. [Clinical significance of plasma total cholesterol, free cholesterol and esterified cholesterol levels]. Nihon Rinsho. 2004;62 Suppl 12:10-3 pubmed
  36. Wang M, Briggs M. HDL: the metabolism, function, and therapeutic importance. Chem Rev. 2004;104:119-37 pubmed
  37. Weisweiler P. Low-dose colestipol plus fenofibrate: effects on plasma lipoproteins, lecithin:cholesterol acyltransferase, and postheparin lipases in familial hypercholesterolemia. Metabolism. 1989;38:271-4 pubmed
    ..7%, respectively. This study indicates the complementarity in effectiveness when both drugs were administered together. The appropriate reduction in LDL was combined with the favorable effects on HDL in familial hypercholesterolemia...
  38. Gong E, Nichols A, Forte T, Blanche P, Shore V. Transformation of large discoidal complexes of apolipoprotein A-I and phosphatidylcholine by lecithin-cholesterol acyltransferase. Biochim Biophys Acta. 1988;961:73-85 pubmed
    ..The deformable species observed during transformation were similar in size and shape to particles observed in interstitial fluid. ..
  39. Pahl M, Ni Z, Sepassi L, Moradi H, Vaziri N. Plasma phospholipid transfer protein, cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase in end-stage renal disease (ESRD). Nephrol Dial Transplant. 2009;24:2541-6 pubmed publisher
    ..These findings point to acquired LCAT and Apo A-1 deficiencies and tend to exclude dysregulation of PLTP or CETP in the pathogenesis of HDL abnormalities in haemodialysis patients. ..
  40. Barlage S, Frohlich D, Bottcher A, Jauhiainen M, Muller H, Noetzel F, et al. ApoE-containing high density lipoproteins and phospholipid transfer protein activity increase in patients with a systemic inflammatory response. J Lipid Res. 2001;42:281-90 pubmed
    ..In summary, the increase in apoE HDL and PLTP activity may improve the delivery of energy substrates and phospholipids to tissues that must maintain cellular membrane homeostasis under conditions of inflammatory stress. ..
  41. Dullaart R, Perton F, Sluiter W, de Vries R, Van Tol A. Plasma lecithin: cholesterol acyltransferase activity is elevated in metabolic syndrome and is an independent marker of increased carotid artery intima media thickness. J Clin Endocrinol Metab. 2008;93:4860-6 pubmed publisher
    ..Plasma LCAT activity is elevated in MetS and may be a marker of subclinical atherosclerosis. Our findings do not support the contention that strategies to elevate LCAT are necessarily beneficial for cardioprotection. ..
  42. Rogers D, Brouillette C, Engler J, Tendian S, Roberts L, Mishra V, et al. Truncation of the amino terminus of human apolipoprotein A-I substantially alters only the lipid-free conformation. Biochemistry. 1997;36:288-300 pubmed
  43. Hirano K, Kachi S, Ushida C, Naito M. Corneal and macular manifestations in a case of deficient lecithin: cholesterol acyltransferase. Jpn J Ophthalmol. 2004;48:82-4 pubmed
  44. Zhang J, Zeng W, Chen B, Wu G, Zhang W, Zhang K. [Analysis of lecithin-cholesterol acyltransferase cDNA and protein sequence from tree shrew]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002;24:149-55 pubmed
    ..The sequence of LCAT cDNA in tree shrew has high identity with that of human and other experimental animal species. ..
  45. Serdyuk A, Metelskaya V, Ozerova I, Kovaltchouk N, Olferiev A, Bubnova M, et al. Effects of alcohol on the major steps of reverse cholesterol transport. Biochemistry (Mosc). 2000;65:1310-5 pubmed
    ..The effects of alcohol on the reverse cholesterol transport depend on the initial HDL C level. ..
  46. Helisten H, Höckerstedt A, Wahala K, Tiitinen A, Adlercreutz H, Jauhiainen M, et al. Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid esters in low-density lipoprotein particles. J Clin Endocrinol Metab. 2001;86:1294-300 pubmed
  47. Mythili Y, Sudharsan P, Sudhahar V, Varalakshmi P. Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced hyperlipidemic cardiomyopathy. Eur J Pharmacol. 2006;543:92-6 pubmed
    ..Supplementation of lipoic acid reverted these abnormalities in the lipid levels and activities of lipid metabolizing enzymes to near normalcy after cyclophosphamide administration. ..
  48. Sviridov D, Hoang A, Ooi E, Watts G, Barrett P, Nestel P. Indices of reverse cholesterol transport in subjects with metabolic syndrome after treatment with rosuvastatin. Atherosclerosis. 2008;197:732-9 pubmed
  49. Klein H, Lohse P, Duverger N, Albers J, Rader D, Zech L, et al. Two different allelic mutations in the lecithin:cholesterol acyltransferase (LCAT) gene resulting in classic LCAT deficiency: LCAT (tyr83-->stop) and LCAT (tyr156-->asn). J Lipid Res. 1993;34:49-58 pubmed
    ..In summary, we have identified two unique defects in the LCAT gene that lead to the expression of classic LCAT deficiency in this kindred. ..
  50. Miida T. [Detection of qualitative abnormalities of HDL by measurement of prebeta1-HDL concentration]. Rinsho Byori. 2006;54:1241-6 pubmed
    ..We determined the LCAT-dependent conversion rate of prebeta1-HDL to detect abnormal HDL metabolism. In this review, we discuss the physiological role of prebeta1 HDL and the clinical significance of plasma prebeta1-HDL concentration. ..
  51. Dominiczak M. Deteriorating fuel metabolism, inflammation and coronary disease: are we closer to an all-encompassing theory?. Curr Opin Lipidol. 2003;14:639-42 pubmed
  52. Bielicki J, Knoff L, Tribble D, Forte T. Relative sensitivities of plasma lecithin:cholesterol acyltransferase, platelet-activating factor acetylhydrolase, and paraoxonase to in vitro gas-phase cigarette smoke exposure. Atherosclerosis. 2001;155:71-8 pubmed
    ..Based on these results, we propose that cigarette smoke may contribute to atherogenesis by inhibiting the activities of plasma PAF-AH and LCAT, but the nature of this inhibition differs for the enzymes. ..
  53. Vaziri N, Liang K, Parks J. Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome. Am J Physiol Renal Physiol. 2001;280:F823-8 pubmed
    ..Therefore, proteinuria, not hypoalbuminemia, causes LCAT deficiency and a depressed HDL-to-total cholesterol ratio in NS. ..