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Cholesterol Metabolism PowerPoint Presentation

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Published on : Dec 06, 2013
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Slide 1 - Cholesterol Metabolism Sources of cholesterol Cholesterol synthesis Long and short term regulation SREBP-2 Lowering cholesterol Calculating your risk for CHD
Slide 2 - Roles of Cholesterol Membrane component Steroid synthesis Bile acid/salt precursor Vitamin D precursor
Slide 3 - Sources of Cholesterol Diet De novo synthesis Cholesterol synthesized in extrahepatic tissues Liver cholesterol pool Free cholesterol In bile Conversion to bile salts/acids Secretion of HDL and VLDL
Slide 4 - Cholesterol Structure FA for esterification
Slide 5 - Dietary Cholesterol Animal products – eggs Absorb about 50% Increase intake = decreased absorption Excrete – 1 g/day (bile acids)
Slide 6 - Dietary Cholesterol Assume 400 mg intake / day 200 mg is absorbed 1000 mg is excreted 800 mg from de novo synthesis Lowering cholesterol in diet has very little effect on blood cholesterol !!!
Slide 7 - Cholesterol Synthesis Similar to ketogenic pathway Occurs in cytosol Requires NADPH and ATP Highly regulated 80 % in liver, ~10% intestine, ~5% skin
Slide 8 - Cholesterol Synthesis
Slide 9 - HMG CoA Reductase : Regulation Short-term regulation Inhibited by phosphorylation AMP-dependent protein kinase When AMP is high (or ATP low!), why waste energy on cholesterol synthesis Long-term regulation Proteolysis Degradation stimulated by cholesterol and cholesterol metabolites Sterol-sensing domain
Slide 10 - HMG CoA reductase - Phosphorylation AMP-Activated Protein Kinase (high activity) AMP-Activated Protein Kinase (low activity) phosphatase insulin (+) kinase Glucagon/epi (+) increase cAMP AMP (+) HMG CoA reductase – OH (active) HMG CoA reductase – P (inactive)
Slide 11 - Transcriptional regulation SREBP-2 Responds to cellular levels of sterols HMG CoA Reductase : Regulation
Slide 12 - SREBP cleavage activating protein
Slide 13 - Site 1 and site 2 protease -
Slide 14 - ppt slide no 14 content not found
Slide 15 - Free Cholesterol Pool synthesis Negative Feedback (-) LDL receptor LP Negative Feedback (-) acat CE HDL Steroid synthesis C
Slide 16 - Lowering Cholesterol Statins – decrease HMG CoA reductase activity Muscle weakness Why?
Slide 17 - Bile sequestering agents Lowering Cholesterol Bile acids liver Bile acids 95 % reabsorbed 5% in feces Bind bile acid Utilize more cholesterol to make bile acids >10% in feces
Slide 18 - Lowering Cholesterol Oat bran Soluble fiber Bind bile acids? Niacin 3-8 grams / day (need 60 mg) Inhibits VLDL excretion ? (fatty liver) Flushing and liver damage
Slide 19 - Unsaturated fats and Cholesterol
Slide 20 - Calculate your risk