Lecture 38

• 1. dietary cholesterol
• 2. extrahepatic de novo synthesis
• 3. liver de novo synthesis

• 1. unmodified cholesterol secreted in bile
• 2. converted to bile acids/salts
• 3. secreted as plasma lipoproteins (VLDL)

All tissues (but liver, intestine, adrenal cortex and reproductive tissues make the largest contributions)

Fed state (synthesis requires high energy carriers ATP and NADPH)

• 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

• They are structural analogs of HMG CoA, and are reversible competetive inhibitors of HMG CoA reductase
• They decrease plasma cholesterol levels

• cholic acid
• chenodeoxycholic acid

• glycocholic acid
• taurochenodeoxycholic acid

• digestion and absorption of dietary lipids
• excretion of hydrophobic waste products in bile

• 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)

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

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

• 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

• Laparoscopic cholecystectomy
• administration of exogenous chenodeoxycholic acid