Cholesterol

Question 1

What is in cholesterol synthesis?

Answer 1

1) synthesis of isopentenyl pyrophosphate
2) condensation to form squalene
3) cyclisation and demethylation of squalene → cholesterol

Question 2

How is isopentenyl synthesised (first 3 steps)?

Answer 2

-occurs in the cytoplasm

1) 2 x acetyl CoA condense → acetoacetyl CoA (4C)
2) acetoacetyl CoA + acetyl CoA → HMG-CoA
3) HMG-CoA reductase reduces HMG-CoA → mevalonate (NADPH → NADP+)

Question 3

What are the final three steps of isopentenyl synthesis?

Answer 3

1) sequential phosphorylations of mevalonate

2) decarboxylations → isopentenyl synthesis

Question 4

What are the three steps in the synthesis of squalene from isopentenyl pyrophosphate?

Answer 4

-cytoplasm

1) isomerism
2) 2 condensation reactions → 15C chain species
3) 2 of these then further condense → squalene (30C) + pyrophosphate

Question 5

What are the four steps in the last step of cholesterol synthesis from squalene?

Answer 5

-take place in the ER

1) squalene reduced with oxygen + NADPH → molecule with a different c=c distribution
2) enzyme catalyses formation of laosterol
3) formation of the four rings -methyl and hydride shifts along the chain
4) Lanosterol is reduced and 3 methyl units removed (demethylated) = cholesterol

Question 6

how is bile synthesised from cholesterol?

Answer 6

• Cholesterol converted into glycocholate (primary bile salt) and taurolate
• Polar groups attached to cholesterol core unit which form hydrophilic face of the bile salts

Question 7

What are the steps of steroid synthesis from cholesterol?

Answer 7

• precursor pregnenolone is generated from cholesterol

- all 5 classes of steroid hormones come from pregnenolone

Question 8

How is vitamin D synthesis from cholesterol?

Answer 8

• formation of Calcitriol from vitamin D3 (active vit D metabolite)
• functions as a steroid hormone, binding to vitamin D response elements (VDREs) in the promoter of target genes and inducing key genes involved in bone metabolism (ie calcium)

Question 9

What is hypercholesterolaemia and its control?

Answer 9

• when cholesterol transportation is defective
• have cholesterol levels approximately 2-3 times higher
• susceptible to atherosclerosis

Question 10

How do you control hypercholesterolaemia?

Answer 10

1) Inhibition of de novo cholesterol synthesis by the liver (HMG-CoA reductase inhibitor)
2) Reduction of dietary cholesterol absorption by the intestines (resins)

Question 11

What are resins or sequestrants?

Answer 11

prevent reabsorption of cholesterolby the intestine by binding to bile acid-cholesterol complexes

Question 12

What are HMG-CoA-Reducatse inhibitors?

Answer 12

• competitive inhibitor

e. g. statins which stops the production of cholesterol

Question 13

what is important to remember in the the synthesis of cholesterol?

Answer 13

-consumed ATP (the phosphorylation of mevalonate) and used NADPH as reducing power (many different steps)

Question 14

what is the mechanism behind familial hypercholoesterolaemia?

Answer 14

-lack functional receptors that can take up LDL