Cholesterol Flashcards

1
Q

3 main parts of cholesterol synthesis

A
  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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

First reaction in cholesterol biosynthesis

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A

HMG CoA

3 hydroxy 3 methylglutaryl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Enzyme that catalyses production of

3 Hydroxy 3 methylglutaryl CoA

A

HMG CoA synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What reaction does HMG CoA reductase synthesise?

A

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

Mevalonate +2NADP+ CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

HMG CoA Reductase under negative feedback control.

What is responsible?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

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

A

Sequential phosphorylation at OH groups position 3 &5

Decarboxylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Activated isoprene formed

A

3 isopentenyl pyrophosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

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

A
3 isopentenyl pyrophosphate 
Dimethylallyl pyrophosphate 
Geranyl pyrophosphate 
Farnesyl pyrophosphate 
Squalene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Versatility of cholesterol is shown in its ability to synthesise…

A

Bile salts
Steroid hormones
Vitamin D metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Bile salts synthesised from cholesterol

A

Glycocholate

Taurocholate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Steroid hormones synthesised from cholesterol

A

Glucocorticoids
Mineralocorticoids
Androgens ———> estrogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is vitamin D

A

Group of steroids

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Main source of vitamin D

A

Activity of UV light on 7 Dehydrocholesterol in epidermis of skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

FH

A

Familial hypercholesterolaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Familial Hypercholesterolaemia

A

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

17
Q

Heterozygotes for FH

A

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

18
Q

Homozygotes for FH

A

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

19
Q

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

A

Occlusion (Blockage of blood vessel) & myocardial infarction

20
Q

What receptors take up cholesterol in LDL form?

A

LDL receptors (LDLR)

21
Q

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

A

Lack functional LDLRs

22
Q

How to control hypercholesterolaemia

A
  1. Inhibition of de novo cholesterol synthesis by liver.
    HMG CoA reductase inhibitors
  2. Reduction of dietary cholesterol absorption by intestines.
    Resins
23
Q

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

A

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

Lipitor, Crestor

24
Q

How do resins work

A

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