Overview Function component of cell membrane precursor for hormone synthesis steroids vitamin D precursor for bile acid synthesis means of excretion >95% of bile acids are reabsorbed ↑ in bile acid production used as a means to treat hypercholesterolemia cholestyramine resin that binds bile acids in the GI tract and prevents reabsorption increases serum cholesterol usage in bile acid production ↑ regulates LDL receptor Sources dietary intake circulating serum LDL uptake via endocytosis of LDL:LDL receptor complex circulating serum HDL transfer of cholesterol from HDL to hepatocyte via scavenger receptor (SR-B1) high levels of this receptor in hepatocytes steroid producing tissues de novo synthesis occurs in hepatocytes HMG-CoA reductase is rate limiting enzyme inhibited by statins, glucagon, cholesterol activated by insulin Regulation ↑ in intrahepatic [cholesterol] ↓ expression of HMG-CoA reductase ↓ de novo cholesterol synthesis LDL-receptor ↓ in cholesterol-containing LDL uptake from serum scavenger receptor (SR-B1) ↓ cholesterol uptake from HDL Transport cholesterol is fat-soluble ↑ transport by synthesis of a cholesteryl ester dissolves into center of HDL catalyzed by lecithin-cholesterol acyltransferase (LCAT) enzyme in serum activated by apoA-1 of HDL see Apolipoproteins topic Pathology familial hypercholesterolemia defective LDL receptor AD presentation cholesterol deposition in skin xanthelasma in eyelid tendon xanthomas in skin above tendons ↑ risk for coronary heart disease atherosclerosis risk factors (causes of endothelial cell damage) smoking ↑ LDL in serum homocystinemia diabetes protective factors antioxidants vitamin E protects LDL from oxidation process injury to endothelial cells of blood vessels an inflammatory state is induced T-cell activation similar to a granuloma cholesterol in the blood deposits in blood vessels LDL oxidized and phagocytosed by macrophages can become full of cholesterol foam cells fatty streak formed fatty streak enlarges fibrous cap formed smooth muscle and endothelial cells migrate over the fatty streak underlying tissue forms necrotic core cap at risk of rupturing exposes underlying endothelium and causes thrombosis