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Cholesterol Metabolism PowerPoint Presentation

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Tags : Cholesterol Metabolism

Published on : Dec 06, 2013
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Cholesterol Metabolism Presentation Transcript

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

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