Lipoprotein receptors.

Abstract

Lipoprotein receptors are membrane proteins which play a central role in lipid metabolism. Although cells are capable of synthetizing de novo cholesterol from acetate, cholesterol is mostly of food origin or synthetized by the liver. The liver is the only organ which can catabolize the cholesterol and clear it from the circulation into biliary acids. Cholesterol, triglycerides and phospholipids are carried in the blood and in the interstitial fluid in association with specific proteins called apolipoproteins (apo), and form the lipoproteins. Although lipoproteins can be separated by their physico-chemical properties (i.e. density), they are the result of continuous exchanges of lipids and apolipoproteins. Lipoproteins are secreted by the intestine and the liver. Enterocytes and hepatocytes associate, in their endoplasmic reticulum, apolipoproteins and lipids from dietary intake and/or endogenous synthesis to form chylomicrons (intestine) or Very Low Density Lipoproteins (VLDL, in the liver). Lipolysis by the lipases of the triglycerides leads to fatty acids which are delivered to cells by a non-receptor pathway. On the contrary, the delivery of cholesterol to cells is dependent of receptors which recognize the lipoproteins by their protein moiety. Peripheric cells use cholesterol from the Low Density Lipoproteins (LDL, final product of VLDL intravascular catabolism) by the LDL receptor pathway. By this receptor, hepatocytes can also perform the clearance of LDL from the organism. The LDL receptor, or B/E receptor, can recognize lipoproteins by both apo B or apo E. However, other receptors might exist to explain the normal catabolism of apo E- containing lipoproteins in patients genetically deficient in LDL receptor. One of the most characterized candidate protein for chylomicrons receptor is the LRP (LDL receptor Related Protein) which shares a strong homology with some domains of the LDL receptor, and which is shown to be the alpha 2-macroglobulin receptor previously described. Due to the delay in clearance by the liver, LDL can undergo oxidation. Oxidized LDL are not recognized by LDL receptor but rather "scavenger" receptors in macrophages and vascular endothelial smooth muscle cells. This metabolism leads to the formation of atherosclerotic plaques. High Density Lipoproteins (HDL) are implicated in the removal of excess cholesterol from peripheral cells and the transport to the liver. Specific HDL binding sites to several mammalian cells have been shown by numerous investigators and one candidate protein has been cloned. Analysis of HDL-induced signal transduction has been a very active field of research.(ABSTRACT TRUNCATED AT 400 WORDS)