Week 3- Cholesterol

Question 1

Describe the structure of cholesterol

Answer 1

Steroid, 27 carbon atoms, planar rings and hydrophobic tail, overall very hydrophobic

Question 2

What is then recommended daily cholesterol intake?

Answer 2

500 mg

Question 3

What is the role of cholesterol?

Answer 3

Regulating membrane fluidity

Question 4

Describe the pathway for the synthesis of cholesterol

Answer 4

STAGE 1
2x acetyl coA goes to acetoacyl coA via condensation
Acetoacyl coA goes to hmg coA via condensation
Hmg coA goes to mevalonate via reduction by enzyme hmg coA reductase (NADPH is used as a source of reducing power and hmg coA is under intense negative feedback from cholesterol and mevalonate)
Mevalonate goes to isopentyl pyrophospate via phosphorylation at position 3 and 5 (requires ATP)

STAGE 2
Isopentyl pyrophosphate is isomerised to form dimethylallyl pyrophosphate
Dimethylallyl and isopentyl pyrophosphate condense to form farnesyl pyrophosphate (15C)
2 molecules of farnesyl pyrophosphate condense to form squalene (30C)

STAGE 3
Squalene is reduced to squalene epoxide using O2 and NADPH
Squalene epoxide is converted to lanesterol via enzyme squalene epoxide lanesterol cyclase
Lanesterol is rid of 3 methyl groups to give cholesterol (27C)

Question 5

What are the 3 stages for the synthesis of cholesterol?

Answer 5

1: synthesis of isopentyl pyrophosphate
2: synthesis of squalene
3: cyclisation and demethylation of squalene to form cholesterol

Question 6

What 2 external molecules are required to synthesize cholesterol and at what stages in the synthesis pathway?

Answer 6

ATP- to phosphorylate mevalonate at position 3 and 5 to form isopentyl pyrophosphate

NADPH- to reduce hmg coA to mevalonate and to reduce squalene to squalene epoxide

Question 7

What are common uses that display the versatility of cholesterol

Answer 7

Bile salt synthesis, vitamin D synthesis and steroid hormone synthesis

Question 8

How are bile salts synthesized?

Answer 8

They are a common product of cholesterol breakdown

Question 9

What are the 2 main bile salts called?

Answer 9

Glycocholate

Taurocholate

Question 10

Why is vitamin D important?

Answer 10

It is required for the absorption of essential ions such as calcium, magnesium and potassium

Question 11

What is calcitrol and why is it important?

Answer 11

It is an important vitamin D metabolite that allows for calcium absorption (a steroid hormone that binds to vit D)

Question 12

How does rickets arise?

Answer 12

Deficiency of vit D3 in childhood

Question 13

How are steroid hormones synthesized from cholesterol?

Answer 13

Cholesterol gives rise to pregnolone which is a precursor for all 5 classes of steroid hormones

Question 14

What are the 5 classes of steroid hormones?

Answer 14

Androgens, oestrogens, progestogens, glucocorticoids, mineralocorticoids

Question 15

What is the inheritance pattern of familial hypercholesterolemia?

Answer 15

Monogenic dominant

Question 16

What happens in familial hypercholesterolemia?

Answer 16

There is reduced expression of LDL receptors so LDL cholesterol is not effectively absorbed leading to high levels in the blood

Question 17

How is pregnolone made?

Answer 17

From cholesterol via enzyme desmolase

Question 18

What are visible symptoms of familial hypercholesterolemia?

Answer 18

Yellow/orange xanthomas on the wrists and knees that arise from scavenging of LDL

Question 19

How is familial hypercholesterolemia treated?

Answer 19

By reducing de novo synthesis of cholesterol by the liver or by reducing dietary cholesterol absorption using hmg coA reducatse inhibitors or statins