Lecture 01

• What is the primary function of cholesterol in cell membranes?

  Adds rigidity to cell membranes
• What is cholesterol a precursor for?

  Steroid hormones
• What is cholesterol used as raw material for?

  Bile salts and vitamin D
• What is the structural basis of cholesterol?

  Based on a four-ring structure
• How many carbon atoms does cholesterol contain?

  27 carbon atoms
• From what is cholesterol derived?

  Solely from acetyl CoA
• What are the three stages of cholesterol synthesis?

  Formation of isopentenyl pyrophosphate, condensation to squalene, cyclisation
• Where does Stage 1 of cholesterol synthesis occur?

  In the cytoplasm
• Where do Stages 2 and 3 of cholesterol synthesis occur?

  On the endoplasmic reticulum
• What is the first step in Stage 1 of cholesterol synthesis?

  Formation of 3-hydroxy-3-methylglutaryl CoA (HMG CoA)
• What is the enzyme involved in the formation of HMG CoA?

  3-ketothiolase
• What is the second step in Stage 1 of cholesterol synthesis?

  Reduction to mevalonate
• What enzyme is responsible for the reduction to mevalonate?

  HMG-CoA reductase
• What is the third step in Stage 1 of cholesterol synthesis?

  Conversion to isopentenyl pyrophosphate
• How many NADPH and ATP are used in Stage 1?

  Uses 2 NADPH and 3 ATP
• What is the first step in Stage 1, Step 1a?

  Formation of acetoacetyl CoA
• What is the enzyme involved in the formation of acetoacetyl CoA?

  3-ketothiolase
• What occurs in Stage 1, Step 1b?

  Condensation with acetyl CoA to form HMG-CoA
• What enzyme catalyses the condensation with acetyl CoA?

  HMG CoA synthase
• What is the process in Stage 1, Step 2?

  Reduction to mevalonate
• What is the role of the enzyme HMG-CoA reductase?

  Reduction to mevalonate
• What happens in Stage 1, Step 3?

  Formation of isopentenyl pyrophosphate
• How is squalene synthesized in Stage 2?

  Synthesized from 6 molecules of IPPP
• What is the first step in Stage 2 of cholesterol synthesis?

  Isomerisation to dimethylallyl pyrophosphate
• What enzyme is involved in the condensation to C10 in Stage 2?

  Geranyl transferase
• What is formed during the condensation to C10?

  Geranyl pyrophosphate
• What occurs in Stage 2, Step 3?

  Further condensation to C15
• What is formed during the further condensation to C15?

  Farnesyl pyrophosphate
• What is the final step in Stage 2?

  Reductive condensation of 2 farnesyl pyrophosphate to make squalene
• What enzyme is involved in the reductive condensation to make squalene?

  Squalene synthase
• What is the role of NADPH in Stage 3 of cholesterol synthesis?

  Used in cyclisation
• What is formed during Stage 3 of cholesterol synthesis?

  Lanosterol
• What triggers cyclisation in Stage 3?

  Addition of proton to oxygen
• What enzyme catalyses the cyclisation process?

  Oxidosqualene cyclase
• What is the final product of the complex process following lanosterol?

  Cholesterol
• What is the sterol structure of cholesterol?

  Sterol with 27 carbon atoms and 4 rings
• How is cholesterol synthesized?

  Synthesised from acetyl CoA
• What are the intermediates in cholesterol synthesis?

  Isopentenyl phosphate, squalene, lanosterol
• What regulates cholesterol synthesis?

  HMG CoA reductase
• How is the transcription of HMG CoA reductase activated?

  By low levels of intracellular cholesterol