生物化学教学课件：Metabolism of Lipids.pptVIP

? Effects of LDL Uptake by Peripheral Cells 1.* Cholesterol gets incorporated  into membranes 2. Cholesterol inhibits HMG- CoA reductase 3. Extra cholesterol may be  stored as cholesterol esters 4. Excess cholesterol represses  the gene for LDL receptor  synthesis Drugs such as Lovastatin, that block cholesterol synthesis by inhibiting HMG-CoA Reductase, cause increased synthesis of LDL receptors. ACAT * Cholesterol converts to steroid hormone,bile salts LDL receptor The LDL receptor was identified by M. Brown J. Goldstein, who were awarded the Nobel Prize for this achievement in 1985. The LDL receptor The LDL receptor was identified by M. Brown J. Goldstein, who were awarded the Nobel Prize for this achievement in 1985. Based on work on familial hypercholesterolemia LDL receptor also called apoB/E receptor because of its ability to recognize particles containing apo B100 or E Activity occurs mainly in the liver exterior side of the plasma membrane The LDL receptor is a single-pass transmembrane glycoprotein. Mutations affecting the LDL receptor are associated with the most common form of the disease familial hypercholesterolemia (high blood cholesterol). Cells with defective LDL receptor cannot take up LDL. As a result, the amount of circulating LDL increases, leading to enhanced risk of developing atherosclerosis. Other hereditary hypercholesterolemias relate to genetic defects in structure of apolipoproteins. E.g., familial defective apoprotein B100 leads to impaired binding of LDL to cell surface receptors, with elevated levels of circulating LDL. Cholesterol, Lipoproteins and Atherosclerotic Disease ? A high total cholesterol (≥ 240 mg/dl) and/or a high LDL (≥160 mg/dl) significantly increase the risk of developing atherosclerotic disease. So LDL are often referred to as the “Bad cholesterol”. e.g. ox-LDL Scavenger receptor pathway LDL receptor-mediated pathway 4. High Density Lipoprotein (HDL) Hig