Cholesterol

Question 1

How many carbon atoms compose cholesterol?

Answer 1

27 carbon atoms

Question 2

What is the structure of cholesterol?

Answer 2

27 carbon atoms, consists of cyclic rings with a hydrophobic tail steroid ring
C3 hydroxyl group

Question 3

Why is cholesterol important?

Answer 3

Fluid dynamics within phospholipid bilayer, enables mechanical stability & fluidity

Question 4

How does cholesterol maintain fluid stability within the phospholipid bilayer?

Answer 4

The cholesterol ring system interferes with motions of the fatty acid side chains

Question 5

What is the first step of cholesterol synthesis?

Answer 5

Isopentenyl pyrophosphate- activated isoprene synthesis

Question 6

What is the second stage of cholesterol synthesis?

Answer 6

Condensation of 6 molecules of isopentenyl pyrophosphate to form squalene (cytoplasmic reactions)

Question 7

What is the fate of squalene?

Answer 7

Squalene undergoes demethylation and cyclisation to give cholesterol by monooxygenases

Question 8

How is isopententyl pp formed (stage 1 &2)?

Answer 8

Two molecules of acetyl-CoA condense to form four carbon acetyoacyl-CoA

This is added to acetyl-CoA

Forms 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA)

Question 9

What happens to HMG-CoA?

Answer 9

HMG-CoA reductase reduces HMG-CoA into Mevalonate

Question 10

Which molecule provides the reducing power for the reduction of HMG-CoA into Mevalonate?

Answer 10

NADP+

Question 11

Where does reduction HMG-CoA occur within a cell?

Answer 11

Within the cytoplasm

Question 12

What is the fate of mevalonate?

Answer 12

Undergoes sequential phosphorylation at hydroxyl groups attached to c3 and c5 by kinase; decarboxylated into Isopenenyl-PP

Question 13

What molecule is consumed for the phosphorylation of mevalonate?

Answer 13

ATP

Question 14

What is the first step of squalene formation?

Answer 14

2 molecules of isopentenyl-PP condense to form dimethylallyl-pp

Question 15

What happens to dimethylallyl-pp?

Answer 15

Addition of isopentenyl to form 15 carbon species

Question 16

What enzyme catalyses the farnesyl-pp reaction?

Answer 16

Geranyl transferase

Question 17

What is the term for the 15 carbon compound formed from 3 isopentenyl-pp?

Answer 17

Farnesylpp

Question 18

How is squalene formed?

Answer 18

2 molecules of Farnesyl-pp condense, by squalene synthetase

Question 19

Where does demethylation and cyclisation of squalene occur?

Answer 19

Endoplasmic reticulum

Question 20

What is the fate of squalene?

Answer 20

Reduced in the presence of oxygen and NADPH, forms squalene epoxide

Question 21

How is cholesterol formed from squalene?

Answer 21

Squalene –> squalene epoxide –> lanosterol –> cholesterol

Question 22

What does cholesterol decompose into?

Answer 22

Glycocholate, taurocholate

Question 23

What are steroid hormones derived from?

Answer 23

Cholesterol

Question 24

What 5 classes of steroid hormones derive from cholesterol?

Answer 24

Oestrogens
Androgens
Corticosteroids
Mineralcorticoids
Progesterones

Question 25

What is the role of cholesterol in vitamin-D synthesis?

Answer 25

7-dehydrodcholesterol within epidermis –> provitamin-d3 –> Vitamin-d3 –> calcitriol

Question 26

What is familial hypercholesteroaemia?

Answer 26

Monogenic dominant trait, cholesterol transportation is defective

Question 27

What type of mutation is FH?

Answer 27

Loss of function in the LDL-receptor gene

Question 28

How can FH be controlled?

Answer 28

Inhibition of de no cholesterol synthesis in the liver

Reduction of dietary cholesterol absorption

Question 29

What drug can reduce cholesterol synthesis?

Answer 29

HMG-CoA Reductase inhibitors and resins

Question 30

What is lovastatin?

Answer 30

Statins are a competitive inhibitor of HMG-CoA reductase, resembles 3-HMG, thus mevalonate cannot be synthesised

Question 31

What are resins (cholestryamine) ?

Answer 31

Bind or sequester bile-acid cholesterol complexes, prevents their reabsorption by the intestine