Lipid 5

• What is the structure of cholesterol's core ring?

  Cyclopentanoperhydrophenanthrene ring
• Which tissues synthesize cholesterol in humans?

  Liver, intestine, adrenal cortex, reproductive tissues
• What drives the synthesis pathway of cholesterol?

  Hydrolysis of thioester bond of acetyl CoA
• How does the synthesis pathway respond to cholesterol levels?

  It adjusts based on cholesterol concentration
• What are the regulatory mechanisms for cholesterol synthesis?

  • Balances synthesis rate with excretion rate
  • Feedback regulation based on cholesterol levels
  • Hormonal regulation (glucagon & insulin)
• What is the preferred storage form of cholesterol?

  Cholesteryl ester
• Why is cholesteryl ester preferred for storage?

  Due to its compact structure and high hydrophobicity
• What compounds are derived from cholesterol?

  • Cholesterol esters
  • Bile acids/salts
  • Steroid hormones (testosterone, estrogens)
  • Ergosterol (precursor for vitamin D)
  • Fat-soluble vitamins (A, E, K)
  • Coenzyme Q (ubiquinone)
• What are the steps of cholesterol synthesis?

  1. Synthesis of mevalonate from acetyl CoA
  2. Formation of isopententenyl pyrophosphate
  3. Formation of squalene
  4. Cyclization of squalene to form lanosterol
  5. Formation of cholesterol
• Where does cholesterol synthesis occur in the cell?

  Cytosol of the cell
• What is the committed step in cholesterol synthesis?

  Reduction of HMG-CoA to mevalonate
• What regulates the committed step in cholesterol synthesis?

  HMG-CoA reductase activity
• How is mevalonate formed from acetyl CoA?

  Through hydration and reduction processes
• What happens during the formation of isopentenyl pyrophosphate?

  Mevalonate is phosphorylated using ATP
• What is the role of squalene in cholesterol synthesis?

  Squalene folds into a steroid-like structure
• What changes occur during the formation of cholesterol?

  Changes in the steroid nucleus and side chain
• What regulates cholesterol synthesis?

  • Feedback regulation based on cholesterol levels
  • Hormonal regulation (glucagon & insulin)
  • Inhibition by drugs (e.g., statins)
  • Sterol-dependent gene expression regulation
• What is the effect of glucagon during starvation on cholesterol synthesis?

  Stimulates phosphorylation of HMG-CoA reductase
• What happens to HMG-CoA reductase during well-fed conditions?

  It becomes active through dephosphorylation
• What inhibits HMG-CoA reductase activity?

  High dietary cholesterol and statins
• How is cholesterol excreted from the body?

  Via bile in feces
• Why can't humans metabolize cholesterol's ring structure?

  It cannot be broken down in humans
• What is the composition of bile?

  Water, bile salts, bilirubin, fats, cholesterol
• What are the conjugated bile acids formed from cholesterol?

  • Glycocholic acid
  • Glycochenodeoxycholic acid
  • Taurocholic acid
  • Taurochenodeoxycholic acid
• What is the action of intestinal bacteria on bile salts?

  They deconjugate and convert bile acids
• What triggers the release of bile juice into the intestine?

  Hormonal signals from fatty food presence
• What happens to bile salts in the intestine?

  They are reabsorbed in the terminal ileum
• What is the clinical importance of bile salt deficiency?

  • Can lead to cholelithiasis (gallstones)
  • Regulates cholesterol secretion into bile
  • Excess cholesterol can precipitate in gallbladder
• What is the pathway for the formation of squalene?

  IPP to dimethylallyl diphosphate to squalene
• What is the final product of cholesterol synthesis?

  Cholesterol