cholsterol metabolism Pharm 11-6-12

cholsterol metabolism Pharm 11-6-12 - Cholesterol Bile Acid...

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Cholesterol & Bile Acid Metabolism George Loucas Tzanis, MD Chief of Primary Care, Philadelphia VAMC Perelman School of Medicine, University of Pennsylvania Diplomate, American Board of Clinical Lipidology
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An accumulation of cholesterol in blood vessel walls
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Overview of this lecture Cholesterol and Related Molecules Sterols Dietary Cholesterol Enterohepatic Circulation Cholesterol Synthesis & Regulation HMG CoA Reductase Elimination of Cholesterol LDL receptor Bile Acids Pharmacological Considerations Drugs that increase LDL uptake Other drugs
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Biochemistry Polar Esterification Hydrophobic Rigid A B C D
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Cholesterol Crystals
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Cholesterol Esters = FFA + Cholesterol O CH 3 CH 3 H H H CH 3 H 3 C CH 3 H O Very hydrophobic The predominant dietary form Stored in lipid droplets within cells Not always always always
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Bile acids are detergents Polar Polar Polar P o l a r Rigid & hydrophobic
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There’s just something about cholesterol TOXIC Chemically similar, physiologically different
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The function of cholesterol Concentration modulates permeability & rigidity in a membrane Concentrated in “lipid rafts” oxysterol
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Location of Cholesterol in Cells Intracellular membranes Lipid Droplets: Storage as ester Plasma Membrane: Intracellular membranes LDL particle
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Which has more cholesterol? Cheese or Steak.
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Source Total Ester % Beef Liver: 262 48% Cooked beef: 62 50% Lard: 143 48% Bacon: 215 71% Pork: 98 72% Turkey 110 54% Egg 1862 19% Shrimp 138 8% Flounder 41 46% Oyster 112 44% Butter 187 54% Cheese 173 11% Milk 28 0%
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Dietary Cholesterol & Fat Pre-fabricated Energy & Carbon Lipoprotein derived cholesterol Synthesized 250mg 250mg 500mg
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Relevant Anatomy & Physiology Gut dietary cholesterol fecal cholesterol Blood Bile Liver Lymph TISSUES TISSUES Lecture 1 Lecture 2
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Oil & water don’t mix
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Oil, Detergent & Water Interface micelle
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Sterols in the gut lumen Cholesterol Bile Acid Phytosterol
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Intestinal Absorption NPC1-L1 cholesterol phytosterols phytosterols ABCG5/8 Lymph Portal Blood ACAT MTP stool
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Dietary Cholesterol Absorption Digestion of free cholesterol & esters Digestion Micelle formation Transport into enterocyte by NPC1-L1 Re-esterification by ACAT Incorporation into chylomicron Entry of chylomicra into the lymphatics Entry of bile acids into the blood
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  • Fall '12
  • lipsh
  • bile acids, HMG CoA reductase, HMG

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