Cholesterol

Question 1

Outline the structure of cholesterol

Answer 1

• Composed of 27 carbon atoms. Arrange in cyclic rings with a hydrophobic tail.
• Ring structure is planar.
• Molecule is very hydrophobic except for hydroxyl group at carbon 3.

Question 2

Where is the majority of cholesterol found in our bodies?

Answer 2

Around 90% of cholesterol is found in cell membranes

Question 3

What is the main function of cholesterol in cell membranes?

Answer 3

Changing membrane stiffness depending on factors such as temperature and nature of the membrane.

Question 4

How can the 3 stages of cholesterol production be summarised?

Answer 4

Stage 1 - synthesis of isopentenyl pyrophosphate in cytoplasm

Stage 2 - synthesis of squalene by condensing 6 molecules of isopentenyl pyrophosphate in cytoplasm

Stage 3 - Cyclisation and demethylation of squalene by monooxygenases to form cholesterol. Occurs in endoplasmic reticulum.

Question 5

How is isopentenyl pyrophosphate formed?

Answer 5

1. 2 molecules of acetyl CoA condense to form acetoacetyl CoA using beta ketothiolase.
2. Acetoacetyl CoA and acetyl CoA condense to form HMG-CoA using HMG-CoA synthase.
3. HMG-CoA is reduced to form mevalonate using HMG-CoA reductase, oxidising 2 molecules of NADPH.
4. HMG-CoA is inhibited by end product inhibition where cholesterol prevents the synthesis of HMG-CoA by inhibiting the activation of its transcription factor SREBP.
5. Mevalonate undergoes sequential phosphorylation followed by decarboxylation to form 3-isopentenyl pyrophosphate.

Question 6

How is squalene formed in stage 2?

Answer 6

3 molecules of 3-isopentenyl pyrophosphate condense to form farnesyl pyrophosphate using geranyl transferase.

2 molecules of farnesyl pyrophosphate then condense to form squalene using squalene synthase.

Question 7

How is cholesterol formed in stage 3?

Answer 7

These reactions take place in the endoplasmic reticulum.

1. Firstly squalene is reduced using oxygen and NADPH to form squalene epoxide.
2. Squalene epoxide then forms lanosterol using squalene epoxide lanosterol cyclase.
3. Lanosterol is then reduced and demethylated to form cholesterol.

Question 8

Give 3 uses of cholesterol outside of cell membranes

Answer 8

1. Bile salt synthesis
2. Steroid hormone synthesis

Cholesterol is converted into pregnenolone by desmolase which is the precursor to all five classes of steroid hormones. (Progestogens, glucocorticoids, mineralocorticoids, androgens and oestrogens.)

3. Vitamin D synthesis

Formed from the activity of UV light upon 7-dehydrocholsterol in the epidermis of the skin.