Model for Biochemical Studies on the Mechanisms Underlying the Regulation of Cholesterol Synthesis

Abstract

Cultured cells have been shown to be a good model for investigation of the mechanism underlying the regulation of cholesterol synthesis [3, 9]. Such studies have shown that in most extrahepatic cells, intracellular cholesterol synthesis is regulated by the presence of the low density lipoprotein (LDL), which carries most of the cholesterol in human plasma. This LDL is taken up by the cells by a process called receptor-mediated endocytosis. The LDL binds to the cell surface receptor (LDL receptor) in regions of the plasma membrane called coated pits, and the LDL-receptor complex enters the cells by absorptive endocytosis. During this process the coated pits invaginate, forming endocytic vesicles that carry LDL to lysosomes. There, the LDL is hydrolysed which liberates amino acids from the protein component of LDL and the free cholesterol from the lipoprotein cholesteryl esters.