Lecithin cholesterol acyltransferase

Cholesterol transport in circulation and its removal from tissues depends o n the activity of lecithin cholesterol acyltransferase (LCAT). LCAT is a so luble 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-dimensiona l structure of LCAT is not yet known, a partial model now exists that facil itates the study of structure-function relationships of the native enzyme, and of natural and engineered mutants. The LCAT reaction on lipoproteins co nsists of several steps, starting with enzyme binding to the lipoprotein/li pid 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 o f some of the LCAT reaction steps. Finally, overexpression of the human LCA T gene in mice and rabbits has been used to examine the physiologic role of LCAT in vivo and its protective effect against diet induced atherosclerosi s. (C) 2000 Elsevier Science B.V. All rights reserved.