Phosphatidylcholine-sterol acyltransferase

Definition:

Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs). The cholesterol ester is then transported back to the liver. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms. Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF. Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters.

References:

[1]. Yue Zhao, et al. 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. 2003 Dec 2;42(47):13941-9. [Content Brief]

[2]. Derek E Piper, et al. The high-resolution crystal structure of human LCAT. J Lipid Res. 2015 Sep;56(9):1711-9. [Content Brief]

[3]. Junken Aoki, et al. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem. 2002 Dec 13;277(50):48737-44. [Content Brief]

[4]. Veronica Hirsch-Reinshagen, et al. LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins. J Lipid Res. 2009 May;50(5):885-93. [Content Brief]

[5]. A B Kosek, et al. Binding affinity and reactivity of lecithin cholesterol acyltransferase with native lipoproteins. Biochem Biophys Res Commun. 1999 May 19;258(3):548-51. [Content Brief]

[6]. M Liu, et al. Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6035-9. [Content Brief]

[7]. Valeria La Marca, et al. The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells. J Neurochem. 2014 Jul;130(1):97-108. [Content Brief]

[8]. M A Clay, et al. Formation of spherical, reconstituted high density lipoproteins containing both apolipoproteins A-I and A-II is mediated by lecithin:cholesterol acyltransferase. J Biol Chem. 2000 Mar 24;275(12):9019-25. [Content Brief]

[9]. P V Subbaiah, et al. 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. 1996 Jan;37(1):113-22. [Content Brief]

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