Lecithin-cholesterol acyltransferase
| Lecithin-cholesterol acyltransferase | |||||||||||
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| Symbols | LCAT ; | ||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 68042 | ||||||||||
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| Species | Human | Mouse | |||||||||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: LCAT; phosphatidylcholine-sterol O-acyltransferase
Overview
Lecithin-cholesterol acyltransferase is an enzyme that catalyzes the esterification of free cholesterol.
Lecithin + Cholesterol → Lysolecithin + Cholesteryl ester
Historical Perspective
In 1935, Sperry first recognized the esterification of free cholesterol occurred when human plasma was incubated at 37°C and considered it as an enzymatic process since the effect was abolished when the plasma was heated to 55-60°C.[1] In 1962, Glomset identified the enzyme lecithin-cholesterol acyltransferase (LCAT) that accounts for esterification of most of the free cholesterol in plasma.[2]
Biochemistry
Lecithin-cholesterol acyltransferase catalyzes the esterification of the free cholesterol into chlesteryl ester by transferring an acyl chain from the R2 position of a phosphatidylcholine to the 3′-hydroxy residue of cholesterol. Cholesteryl ester 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. Its role in extracellular cholesterol metabolism may facilitate the uptake of cholesterol from peripheral tissues into HDL particles by maintaining a concentration gradient for the efflux of free cholesterol which is centrol to reverse cholesterol transport (RCT). The enzyme is bound to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in the plasma.
See also
References
Further reading
- Kuivenhoven JA, Pritchard H, Hill J; et al. (1997). "The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes". J. Lipid Res. 38 (2): 191–205. PMID 9162740.
- de Vries R, Borggreve SE, Dullaart RP (2004). "Role of lipases, lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in abnormal high density lipoprotein metabolism in insulin resistance and type 2 diabetes mellitus". Clin. Lab. 49 (11–12): 601–13. PMID 14651331.
- Teisberg P, Gjone E, Olaisen B (1975). "Genetics of LCAT (lecithin: cholesterol acyltransferase) deficiency". Ann. Hum. Genet. 38 (3): 327–31. PMID 806250.
- Cogan DG, Kruth HS, Datilis MB, Martin N (1993). "Corneal opacity in LCAT disease". Cornea. 11 (6): 595–9. PMID 1468226.
- Skretting G, Blomhoff JP, Solheim J, Prydz H (1992). "The genetic defect of the original Norwegian lecithin:cholesterol acyltransferase deficiency families". FEBS Lett. 309 (3): 307–10. PMID 1516702.
- Skretting G, Prydz H (1992). "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 (2): 583–7. PMID 1571050.
- Furukawa Y, Urano T, Hida Y; et al. (1992). "Interaction of rat lecithin-cholesterol acyltransferase with rat apolipoprotein A-I and with lecithin-cholesterol vesicles". J. Biochem. 111 (3): 413–8. PMID 1587806.
- Minnich A, Collet X, Roghani A; et al. (1992). "Site-directed mutagenesis and structure-function analysis of the human apolipoprotein A-I. Relation between lecithin-cholesterol acyltransferase activation and lipid binding". J. Biol. Chem. 267 (23): 16553–60. PMID 1644835.
- Bujo H, Kusunoki J, Ogasawara M; et al. (1992). "Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease". Biochem. Biophys. Res. Commun. 181 (3): 933–40. PMID 1662503.
- Gotoda T, Yamada N, Murase T; et al. (1991). "Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency". Lancet. 338 (8770): 778–81. PMID 1681161.
- Klein HG, Lohse P, Pritchard PH; et al. (1992). "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 (2): 499–506. PMID 1737840.
- Maeda E, Naka Y, Matozaki T; et al. (1991). "Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene". Biochem. Biophys. Res. Commun. 178 (2): 460–6. PMID 1859405.
- Funke H, von Eckardstein A, Pritchard PH; et al. (1991). "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. 88 (11): 4855–9. PMID 2052566.
- Taramelli R, Pontoglio M, Candiani G; et al. (1990). "Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele". Hum. Genet. 85 (2): 195–9. PMID 2370048.
- Rogne S, Skretting G, Larsen F; et al. (1987). "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 (1): 161–9. PMID 2823801.
- Tata F, Chaves ME, Markham AF; et al. (1987). "The isolation and characterisation of cDNA and genomic clones for human lecithin: cholesterol acyltransferase". Biochim. Biophys. Acta. 910 (2): 142–8. PMID 2823898.
- Yang CY, Manoogian D, Pao Q; et al. (1987). "Lecithin:cholesterol acyltransferase. Functional regions and a structural model of the enzyme". J. Biol. Chem. 262 (7): 3086–91. PMID 2880847.
- McLean J, Fielding C, Drayna D; et al. (1986). "Cloning and expression of human lecithin-cholesterol acyltransferase cDNA". Proc. Natl. Acad. Sci. U.S.A. 83 (8): 2335–9. PMID 3458198.
- Azoulay M, Henry I, Tata F; et al. (1987). "The structural gene for lecithin:cholesterol acyl transferase (LCAT) maps to 16q22". Ann. Hum. Genet. 51 (Pt 2): 129–36. PMID 3674753.
- McLean J, Wion K, Drayna D; et al. (1987). "Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression". Nucleic Acids Res. 14 (23): 9397–406. PMID 3797244.
External links
- Lecithin+Cholesterol+Acyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)