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What are three sources of cholesterol?
- 1. dietary cholesterol
- 2. extrahepatic de novo synthesis
- 3. liver de novo synthesis
What are three ways cholesterol is eliminated from the liver?
- 1. unmodified cholesterol secreted in bile
- 2. converted to bile acids/salts
- 3. secreted as plasma lipoproteins (VLDL)
Where is cholesterol synthesized?
All tissues (but liver, intestine, adrenal cortex and reproductive tissues make the largest contributions)
When is cholesterol synthesis taking place? Why?
Fed state (synthesis requires high energy carriers ATP and NADPH)
What are the three steps in cholesterol synthesis?
- 1. synthesis of HMG CoA from acetyl CoA and NADPH
- 2. synthesis of mevalonic acid from HMG CoA
- 3. synthesis of cholesterol from mevalonic acid
How do statin drugs work?
- They are structural analogs of HMG CoA, and are reversible competetive inhibitors of HMG CoA reductase
- They decrease plasma cholesterol levels
What are the primary bile acids?
- cholic acid
- chenodeoxycholic acid
What are the bile salts?
- glycocholic acid
- taurochenodeoxycholic acid
What are the functions of bile salts?
- digestion and absorption of dietary lipids
- excretion of hydrophobic waste products in bile
What is the action of intestinal flora on bile salts?
- deconjugate (remove glycine or taurine) the bile salts back into bile acids
- convert primary bile acids into secondary bile acids by removing a hydroxyl group (produces deoxycholic acid and lithocholic acid)
Explain enterohepatic circulation?
continuous process of secretion of bile salts into the bile --> their passage through the duodenum where som are converted to bile acids --> their subsequent return to the liver as a mixture of bile acids and salts
What is the function of cholestyramine?
treatment for hypercholesterolemia, positively charged resin that forms ionic bonds with intestinal bile salts and prevents the re-absorption of bile salts, forces the liver to use more cholesterol for bile synthesis
What is cholelithiasis? How does it happen?
- Cholesterol gallstone disease
- It happens when the dual process of secretion of phophsolipids and bile salts for solubilizing cholesterol is disrupted and more cholesteral enters the bile than can be solubilized by the bile salts and lecithin present and the cholesterol precipitates in the gall bladder
What are the treatment for cholelithiasis?
- Laparoscopic cholecystectomy
- administration of exogenous chenodeoxycholic acid
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