Scavenger receptors uptake
LOW-DENSITY LIPOPROTEINS (LDL) LDL transpos cholesterol from liver to peripheral tissues. The only apoprotein present in LDL is apo B100. Most of the LDL paicles are derived from VLDL, but a small pa is directly released from liver. The half-life of LDL in blood is about 2 days. Metabolism of LDL and LDL Receptors LDL is taken up by peripheral tissues by receptor-mediated endocytosis. LDL receptors are present on all cells but most abundant in hepatic cells. LDL receptors are located in specialised regions called clathrin-coated pitsBinding of LDL to the receptor is by apo-B-100 and uptake of cholesterol from LDL is a highly regulated process. When the apo-B-100 binds to the apo-B-100 receptor, the receptor-LDL complex is internalised by endocytosis. The endosome vesicle thus formed fuses with lysosomes. The receptor is recycled and returns to the cell surface. The LDL paicle, along with apoproteins and cholesterol ester is hydrolysed by lysosomal hydrolases, forming amino acids and free cholesterol. The free receptors can now return to the membrane surface to bind fuher LDL molecules (Fig. 12.13). Approximately 70% of LDL is degraded in the liver, and the rest in extra-hepatic tissues. For their work on LDL receptors, Michael Brown and Joseph Goldstein were awarded Nobel prize in 1985. Function of LDL About 75% of the plasma cholesterol is incorporated into the LDL paicles. LDL transpos cholesterol from liver to the peripheral tissues. The cholesterol thus liberated in the cell has three major fates: i. It is used for the synthesis of other steroids like steroid hormones. ii. Cholesterol may be incorporated into the membranes. iii. Cholesterol may be esterified to a MUFA by acyl cholesterol acyltransferase (ACAT) for storage. The cellular content of cholesterol regulates fuher endogenous synthesis of cholesterol by regulating HMG CoA reductase.LDL and Clinical Applications LDL concentration in blood has positive correlation with incidence of cardiovascular diseases. A fraction of cholesterol is taken up by macrophages, this is not a regulated pathway. Increased levels of LDL or modification of LDL by glycation (as seen in diabetes mellitus) or oxidation increases the fraction of cholesterol taken up by macrophages. LDL infiltrates through aerial walls and is taken up by macrophages or scavenger cells. This is the staing event of atherosclerosis leading to myocardial infarction (see coronary aery diseases in Chapter 25). When these cells become engorged with cholesterol, foam cells are formed, that get deposited in the subendothelial space triggering formation of atheromatous plaque (see Fig. 25.3). Procoagulant changes are induced in the endothelium resulting in increased chances of thrombosis and coronary aery disease (Fig. 25.4). Since LDL-cholesterol is thus deposited in tissues, the LDL (low-density lipoprotein) variety is called "bad cholesterol" and LDL as "Lethally Dangerous Lipoprotein"Ref: DM Vasudevan - Textbook of Biochemistry, 8th edition, page no: 153-154
HDL
VLDL
LDL
IDL
Metabolism of lipid