ABSTRACT
The LDL receptor is the key component in the feed-back regulated maintenance of cholesterol homeostasis in the body (Brown and Goldstein, 1986). In fact, as an active interface between the extra-and intracellular cholesterol pools, it is itself subject to regulation. LDLderived cholesterol and its intracellularly generated
*Corresponding Author: Petri T.Kovanen, Wihuri Research Institute, Kalliolinnantie 4, Helsinki 00140, Finland
oxidized derivatives mediate a complex series of feedback control mechanisms that protect the cell from overaccumulation of cholesterol. First, LDL-derived sterols suppress the activities of 3-hydroxy-3methylglutaryl-CoA (HMG-CoA) synthase and HMG-CoA reductase, the two key enzymes in cellular cholesterol biosynthesis. Second, cholesterol itself activates the cytoplasmic cholesterol-esterifying enzyme acyl-CoA:cholesterol acyltransferase (ACAT; E.G. 2.3.1.26), which allows the cells to store excess cholesterol in the form of cholesteryl esters. Third, the cholesterol contained in LDL particles suppresses the synthesis of new LDL receptors, thus preventing further cellular entry of LDL and cholesterol overloading.
