Cholesterol

Question 1

3 main parts of cholesterol synthesis

Answer 1

1. Synthesis of isopentenyl pyrophosphate
2. Condensation of 6 molecules of isopentyl pyrophosphate to form squalene
3. Cyclisation & demethylation of squalene by monooxygenase to form cholesterol

Question 2

First reaction in cholesterol biosynthesis

Answer 2

Acetyl CoA + Acetyl CoA ➡️ Acetoacetyl CoA
Condensation X 2
B ketothiolase
Breaking thioester bond + CoA leaves

Question 3

What is the product of the reaction between acetoacetyl CoA and acetyl CoA

Answer 3

HMG CoA

3 hydroxy 3 methylglutaryl CoA

Question 4

Enzyme that catalyses production of

3 Hydroxy 3 methylglutaryl CoA

Answer 4

HMG CoA synthase

Question 5

What reaction does HMG CoA reductase synthesise?

Answer 5

HMG CoA +2NADPH +H+ ===)

Mevalonate +2NADP+ CoA

Question 6

HMG CoA Reductase under negative feedback control.

What is responsible?

Answer 6

Mevalonate (product inhibition)
Cholesterol
Bile salts (manufactured from cholesterol)

Question 7

Mevalonate is not activated. What series of reactions (briefly) does it under go to form an activate isoprene?

Answer 7

Sequential phosphorylation at OH groups position 3 &5

Decarboxylation

Question 8

Activated isoprene formed

Answer 8

3 isopentenyl pyrophosphate

Question 9

Name in order the intermediates from
3 isopentenyl pyrophosphate to Squalene.
I did get funny shit

Answer 9

3 isopentenyl pyrophosphate 
Dimethylallyl pyrophosphate 
Geranyl pyrophosphate 
Farnesyl pyrophosphate 
Squalene

Question 10

Versatility of cholesterol is shown in its ability to synthesise…

Answer 10

Bile salts
Steroid hormones
Vitamin D metabolites

Question 11

Bile salts synthesised from cholesterol

Answer 11

Glycocholate

Taurocholate

Question 12

Steroid hormones synthesised from cholesterol

Answer 12

Glucocorticoids
Mineralocorticoids
Androgens ———> estrogens

Question 13

What is vitamin D

Answer 13

Group of steroids

Vital for intestinal absorption of ions needed for bone development e.g calcium, phosphate, magnesium

Question 14

Main source of vitamin D

Answer 14

Activity of UV light on 7 Dehydrocholesterol in epidermis of skin

Question 15

FH

Answer 15

Familial hypercholesterolaemia

Question 16

What is Familial Hypercholesterolaemia

Answer 16

Monogenic dominant trait.
Cholesterol transportation is defective
Body unable to remove LDL/bad cholesterol from blood

Question 17

Heterozygotes for FH

Answer 17

Single copy of mutant gene
Cholesterol levels 2/3 X higher
Susceptible to atherosclerosis (hardening of arteries) in middle age

Question 18

Homozygotes for FH

Answer 18

2 defective copies of gene
Serum cholesterol 5X higher
Severe atherosclerosis & coronary infarction in adolescence

Question 19

What does deposition of LDL derived cholesterol in coronary arteries lead to

Answer 19

Occlusion (Blockage of blood vessel) & myocardial infarction

Question 20

What receptors take up cholesterol in LDL form?

Answer 20

LDL receptors (LDLR)

Question 21

What is notable about the fibroblasts from patients with severe familial hypercholesterolaemia?

Answer 21

Lack functional LDLRs

Question 22

How to control hypercholesterolaemia

Answer 22

1. Inhibition of de novo cholesterol synthesis by liver.
   HMG CoA reductase inhibitors
2. Reduction of dietary cholesterol absorption by intestines.
   Resins

Question 23

How do HMG CoA reductase inhibitors (aka statins) work. Examples.

Answer 23

Competitive inhibitor
E.g lovastatin- part of it resembles the enzyme substrate 3-HMG

Lipitor, Crestor

Question 24

How do resins work

Answer 24

Attach to bile from liver & prevent it from being absorbed back into blood.
Bile - made from cholesterol.
So resins whittle down body’s supply of cholesterol LDL