Lecithin Cholesterol Acyltransferase (LCAT)

phosphatidylcholine-sterol O-acyltransferase; Phospholipid-cholesterol acyltransferase

SPN	O238
HGNC	6522
MGI	96755
PubMed	11797372
RGD	2993
UniProt	P04180
Wiki	LCAT

Lecithin-cholesterol acyltransferase is an enzyme that converts free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL spherical and forcing the reaction to become unidirectional since the particles are removed from the surface. The enzyme is bound to high-density lipoproteins (HDLs) and low-density lipoproteins in the blood plasma.

An unusual feature of the message is that the poly(A) signal appears to overlap the COOH-terminal glutamic acid and stop codons. The protein has several extended sequences of hydrophobic amino acids, one of which is similar to sequences in pancreatic lipase and lingual lipase.

Reference

"Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression."
Nucleic Acids Res. 14:9397-9406(1986) [PubMed] [Europe PMC] [Abstract]

"Cloning and expression of human lecithin-cholesterol acyltransferase cDNA."
Proc. Natl. Acad. Sci. U.S.A. 83:2335-2339(1986) [PubMed] [Europe PMC] [Abstract]

"The sequence and analysis of duplication-rich human chromosome 16."
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The isolation and characterisation of cDNA and genomic clones for human lecithin: cholesterol acyltransferase."
Biochim. Biophys. Acta 910:142-148(1987) [PubMed] [Europe PMC] [Abstract]

"The isolation and characterisation of a cDNA clone for human lecithin:cholesterol acyl transferase and its use to analyse the genes in patients with LCAT deficiency and fish eye disease."
Biochem. Biophys. Res. Commun. 148:161-169(1987) [PubMed] [Europe PMC] [Abstract]

"Lecithin:cholesterol acyltransferase. Functional regions and a structural model of the enzyme."
J. Biol. Chem. 262:3086-3091(1987) [PubMed] [Europe PMC] [Abstract]

"Site-specific detection and structural characterization of the glycosylation of human plasma proteins lecithin:cholesterol acyltransferase and apolipoprotein D using HPLC/electrospray mass spectrometry and sequential glycosidase digestion."
Protein Sci. 4:791-803(1995) [PubMed] [Europe PMC] [Abstract]

"Comparative studies on the substrate specificity of lecithin:cholesterol acyltransferase towards the molecular species of phosphatidylcholine in the plasma of 14 vertebrates."
J. Lipid Res. 37:113-122(1996) [PubMed] [Europe PMC] [Abstract]

"Secretion of lecithin:cholesterol acyltransferase by brain neuroglial cell lines."
Biochem. Biophys. Res. Commun. 258:73-76(1999) [PubMed] [Europe PMC] [Abstract]

"Binding affinity and reactivity of lecithin cholesterol acyltransferase with native lipoproteins."
Biochem. Biophys. Res. Commun. 258:548-551(1999) [PubMed] [Europe PMC] [Abstract]

"Formation of spherical, reconstituted high density lipoproteins containing both apolipoproteins A-I and A-II is mediated by lecithin:cholesterol acyltransferase."
J. Biol. Chem. 275:9019-9025(2000) [PubMed] [Europe PMC] [Abstract]

"Negative charge at amino acid 149 is the molecular determinant for substrate specificity of lecithin: cholesterol acyltransferase for phosphatidylcholine containing 20-carbon sn-2 fatty acyl chains."
Biochemistry 42:13941-13949(2003) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]

"Relationship of endogenous hyperleptinemia to serum paraoxonase 1, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase in obese individuals."
Metabolism 56:1542-1549(2007) [PubMed] [Europe PMC] [Abstract]

"LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins."
J. Lipid Res. 50:885-893(2009) [PubMed] [Europe PMC] [Abstract]

"An amino acid exchange in exon I of the human lecithin: cholesterol acyltransferase (LCAT) gene is associated with fish eye disease."
Biochem. Biophys. Res. Commun. 182:583-587(1992) [PubMed] [Europe PMC] [Abstract]

"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)."
J. Clin. Invest. 89:499-506(1992) [PubMed] [Europe PMC] [Abstract]

"Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele."
Hum. Genet. 85:195-199(1990) [PubMed] [Europe PMC] [Abstract]

"Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency."
Lancet 338:778-781(1991) [PubMed] [Europe PMC] [Abstract]

"The genetic defect of the original Norwegian lecithin:cholesterol acyltransferase deficiency families."
FEBS Lett. 309:307-310(1992) [PubMed] [Europe PMC] [Abstract]

"Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene."
Biochem. Biophys. Res. Commun. 178:460-466(1991) [PubMed] [Europe PMC] [Abstract]

"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."
J. Clin. Invest. 91:677-683(1993) [PubMed] [Europe PMC] [Abstract]

"Lecithin:cholesterol acyltransferase deficiency: identification of a causative gene mutation and a co-inherited protein polymorphism."
Biochim. Biophys. Acta 1181:321-323(1993) [PubMed] [Europe PMC] [Abstract]

"A single G to A nucleotide transition in exon IV of the lecithin: cholesterol acyltransferase (LCAT) gene results in an Arg140 to His substitution and causes LCAT-deficiency."
Hum. Genet. 96:105-109(1995) [PubMed] [Europe PMC] [Abstract]

"Deficiency of lecithin:cholesterol acyltransferase due to compound heterozygosity of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT gene."
Hum. Mol. Genet. 4:143-145(1995) [PubMed] [Europe PMC] [Abstract]

"Two novel molecular defects in the LCAT gene are associated with fish eye disease."
Arterioscler. Thromb. Vasc. Biol. 16:294-303(1996) [PubMed] [Europe PMC] [Abstract]

"Complete deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) activity due to a novel homozygous mutation (Gly-30-Ser) in the LCAT gene."
Hum. Mutat. 8:79-82(1996) [PubMed] [Europe PMC] [Abstract]

"A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol acyltransferase (LCAT) gene in a Japanese patient with LCAT deficiency."
Int. J. Clin. Lab. Res. 26:250-254(1996) [PubMed] [Europe PMC] [Abstract]

"Molecular basis of fish-eye disease in a patient from Spain. Characterization of a novel mutation in the LCAT gene and lipid analysis of the cornea."
Arterioscler. Thromb. Vasc. Biol. 17:1382-1391(1997) [PubMed] [Europe PMC] [Abstract]

"Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency: structure-function relationships and studies in a compound heterozygous proband."
J. Lipid Res. 39:1870-1876(1998) [PubMed] [Europe PMC] [Abstract]

"Hypocomplementemic type II membranoproliferative glomerulonephritis in a male patient with familial lecithin-cholesterol acyltransferase deficiency due to two different allelic mutations."
Nephron 88:268-272(2001) [PubMed] [Europe PMC] [Abstract]

"A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT deficiency and defective apolipoprotein B-100."
Atherosclerosis 170:105-113(2003) [PubMed] [Europe PMC] [Abstract]

"Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors."
Hum. Mol. Genet. 12:2733-2743(2003) [PubMed] [Europe PMC] [Abstract]

"The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families."
Arterioscler. Thromb. Vasc. Biol. 25:1972-1978(2005) [PubMed] [Europe PMC] [Abstract]

"Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family."
Atherosclerosis 185:413-420(2006) [PubMed] [Europe PMC] [Abstract]

"Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol acyltransferase (LCAT) gene results in an intermediate phenotype between LCAT-deficiency and fish-eye disease."
Atherosclerosis 187:101-109(2006) [PubMed] [Europe PMC] [Abstract]

"LCAT deficiency: molecular and phenotypic characterization of an Italian family."
J. Nephrol. 19:375-381(2006) [PubMed] [Europe PMC] [Abstract]

"High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in The Netherlands: identification and characterization of eight novel mutations."
Hum. Mutat. 32:1290-1298(2011) [PubMed] [Europe PMC] [Abstract]