Lecture_18_4-1-10-PDF_41480

Lecture_18_4-1-10-PDF_41480 - Lec17 Lipid Metabolism 7....

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7. Cholesterol Metabolism A. Cholesterol biosynthesis B. Regulation of Cholesterol Synthesis C. Cholesterol Transport and Atherosclerosis Lipid Metabolism Lec17
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Export of Cholesterol Synthesized in Liver •Conversion to bile acids followed by secretion into the small intestine in the bile fluid. (Bile acids function to emulsify dietary lipid.) •Conversion to cholesterol esters , packaging into lipoproteins and export into the blood.
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A. Digestion and absorption Fats need to be “solubilized” in the intestine and bile acids (AKA, bile salts) act as detergents to do this. Bile acids are a derivative of cholesterol and are organic acids. p242 bile acid Lec14
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Role of Bile Acids in Fat Digestion and Absorption Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Bile acids are facial amphipathic , that is, they contain both hydrophobic ( lipid soluble ) and hydrophilic ( water soluble ) faces. hydrophobic hydrophilic Lec14
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Export of Cholesterol Synthesized in Liver •Conversion to bile acids followed by secretion into the small intestine in the bile fluid. (Bile acids function to emulsify dietary lipid.) •Conversion to cholesterol esters , packaging into lipoproteins and export into the blood.
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Synthesis of Cholesterol Esters
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Fig 20-5 (p681) LDL (Low Density Lipoprotein)
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Lipid transport is done in the blood by various lipoprotein particles
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LDL binds to LDL receptors ACAT (acyl CoA:cholesterol acyltransferase) ERC (endocytic recycling compartment) TGN (Trans-Golgi network) Intracellular cholesterol transport
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Atherosclerosis •Obstruction of blood vessels due to pathological accumulation of cholesterol-containing plaques. •Heart failure due to occluded coronary arteries is a major cause of death in industrialized societies. •Incidence of atherosclerosis correlates with high blood concentrations of cholesterol, especially with high levels of LDL. •Incidence of atherosclerosis is negatively correlated with high levels of HDL.
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Microscopic cross-sections of coronary artery narrowed by accumulated lipid and fibrous material Normal
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Gross Specimens Anterior left ventricular wall and septum Cross sections of coronary artery, with narrowing to left http://medstat.med.utah.edu/WebPath/ATHHTML/ATH002.html
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Atherosclerosis •People who have high blood pressure , are cigarette smokers or diabetics and those having high levels of cholesterol are at greater risk of developing this disease. •Prevention of this disease is aided by eliminating the controllable risk factors .
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Familial Hypercholesterolemia Genetic disease that arises from any one of many LDL uptake into cells is defective, which results in cholesterol accumulation in the blood . – Homozygotes: 680 mg/dL (atherosclerosis in childhood) – Heterozygotes: 300 mg/dL (atheroclerosis in middle age) – Healthy Level: 175 mg/dL Treated with inhibitors of de novo cholesterol biosynthesis and Cholestyramine.
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Cells acquire LDL as mediated by the receptor Normal: LDL HDL conversion is all right Cholesterol efflux to form HDL is assisted by the ABCA1 transporter
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Familial hypercholesterolemia A lack of LDL receptor results in high levels of circulating LDL LDL
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Treatment with HMG-CoA competitive inhibitors HMG-CoA reductase
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Inhibitor action substrate inhibitor X X HMG-CoA reductase
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This note was uploaded on 09/15/2010 for the course BCHS 3305 taught by Professor Fujita during the Spring '10 term at University of Houston.

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Lecture_18_4-1-10-PDF_41480 - Lec17 Lipid Metabolism 7....

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