Lecithin cholesterol acyltransferase.
Cholesterol transport in circulation and its removal from tissues depends on the activity of lecithin cholesterol acyltransferase (LCAT). LCAT is a soluble enzyme that converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lyso-phosphatidylcholines on the surface of high-density lipoproteins. This review presents key background information and recent research advances on the structure of human LCAT, its reactions and substrates, and the expression of the LCAT gene. While the three-dimensional structure of LCAT is not yet known, a partial model now exists that facilitates the study of structure-function relationships of the native enzyme, and of natural and engineered mutants. The LCAT reaction on lipoproteins consists of several steps, starting with enzyme binding to the lipoprotein/lipid surface, followed by activation of LCAT by apolipoproteins, binding of lipid substrates and the catalytic steps giving rise to the lipid products. Quantitative data are presented on the kinetic and equilibrium constants of some of the LCAT reaction steps. 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.
Jonas
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Department of Biochemistry, University of Illinois, College of Medicine at Urbana-Champaign, 506 South Mathews Avenue, 61801, Urbana, IL, USA. a-jonas@uiuc.edu
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001161:Arteriosclerosis / Q000201:enzymology; D002240:Carbohydrate Sequence; D002784:Cholesterol / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase