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Cholesterol

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cholesterol metabolism

cholesterol metabolism

Published in: Health & Medicine

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  • 1. M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar
  • 2. Cholesterol Metabolism Sources of cholesterol Cholesterol synthesis Long and short term regulation SREBP-2 Lowering cholesterol Calculating your risk for CHD
  • 3. Roles of Cholesterol Membrane component Steroid synthesis Bile acid/salt precursor Vitamin D precursor
  • 4. Sources of Cholesterol Diet De novo synthesis Cholesterol synthesized in extrahepatic tissues Liver cholesterol pool Free cholesterol In bile Conversion to bile salts/acidsSecretion of HDL and VLDL
  • 5. Cholesterol Structure FA for esterification
  • 6. Dietary Cholesterol Animal products – eggs Absorb about 50% Increase intake = decreased absorption Excrete – 1 g/day (bile acids)
  • 7. 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 !!!
  • 8. Cholesterol Synthesis Similar to ketogenic pathway Occurs in cytosol Requires NADPH and ATP Highly regulated 80 % in liver, ~10% intestine, ~5% skin
  • 9. CHOLESTEROL SYNTHESIS
  • 10. 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
  • 11. 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)
  • 12. HMG CoA Reductase : Regulation Transcriptional regulation SREBP-2 Responds to cellular levels of sterols
  • 13. SREBP cleavage activating protein
  • 14. Site 1 and site 2 protease -
  • 15. Free Cholesterol Pool synthesis Negative Feedback (-) LDL receptor LP Negative Feedback (-) acat CE HDL Steroid synthesis C
  • 16. Lowering Cholesterol Statins – decrease HMG CoA reductase activity Muscle weakness Why?
  • 17. Lowering Cholesterol Bile sequestering agents Bile acids liver Bile acids 95 % reabsorbed 5% in feces NH3+ NH3+ 1. Bind bile acid 2. Utilize more cholesterol to make bile acids >10% in feces
  • 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

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