Mechanisms of action of lecithin-cholesterol acyltransferase

Abstract

Lecithin–cholesterol acyltransferase (LCAT) generates the major part of cholesteryl esters in human plasma from lipoprotein lecithin and unesterified cholesterol. As a practical matter, isolated LCAT is reactive to a significant extent only with the high-density lipoprotein (HDL) class of human plasma lipoproteins. The mechanism of action of LCAT under physiological conditions is quite different from that determined with a fully defined system of synthetic lipids. Because information is insufficient at this point to fully integrate the data that have been obtained with synthetic and physiological substrates, these will first be considered separately. A comparison of the types of data will be made. The most effective direct substrate for LCAT would therefore be one containing phospholipid, apoA-I only, and little cholesteryl ester or free cholesterol. Such a particle has been identified in normal plasma by immunoaffinity chromatography and accumulates in congenital LCAT deficiency. This is the primary substrate for LCAT in vivo , acting as the recipient of free cholesterol from cell membranes, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL), and the source of the cholesteryl esters are transferred away to the major lipoprotein classes of the plasma.