Cholestrol synthesis

Question 1

Where does cholesterol synthesis occur?

Answer 1

in the cytosol

Question 2

How many C atoms does cholesterol contain?

Answer 2

27

Question 3

The carbon source of cholesterol biosynthesis is …..

Answer 3

acetate/acetyl CoA

Question 4

What is the energy source for cholesterol biosynthesis?

Answer 4

Hydrolysis of ATP or acetyl CoA

Question 5

The reducing agent in cholesterol biosynthesis is ………….

Answer 5

NADPH

Question 6

In the absence of ……….. cholesterol synthesis will not occur.

Answer 6

NADPH

Question 7

Step 1

Answer 7

Thiolase catalyses the condensation of 2 acetyl CoA molecules to form acetoacetyl CoA

Question 8

Step 2

Answer 8

Cystolic enzyme, HMG CoA synthase adds another acetyl CoA to acetoacetyl CoA to form a 6C molecule, 3-hydroxy-3-methylglutayrl CoA (HMG CoA)

Question 9

What step is the rate limiting step and why?

Answer 9

Step 3 because it is irreversible

Question 10

Step 3

Answer 10

• Rate-limiting step

- HMG CoA reductase catalyses the reduction of HMG CoA to mevalonic acid(mevalonate) by NADPH

Question 11

What is unique about the location and function of HMGR (HMG CoA reductase)?

Answer 11

found in the membrane of the ER but has its functional domain in the cytosol

Question 12

Step 4

Answer 12

Kinases hydrolyse ATPs to add 2 phosphate groups to mevalonate to from 5-pyrophosphomevalonate

Question 13

What does the phosphorylation of mevalonate do to it?

Answer 13

makes it very a hydrophilic molecule

Question 14

Step 5

Answer 14

• Decarboxylation step

- Decarboxylase uses ATP to decarboxylate 5-pyrophosphomevalonate to isopentenyl pyrophosphate(5C, IPP)

Question 15

Step 6

Answer 15

Isomerase converts IPP to 3,3-dimethylallyl pyrophosphate (DPP)

Question 16

Step 7

Answer 16

Transferase catalyses the condensation of DPP and IPP to form geranyl pyrophosphate (10C,GPP)

Question 17

Step 8

Answer 17

Transferase catalyses another condensation reaction of IPP and GPP to form farnesyl pyrophosphate (15C,FPP)

Question 18

Step 9

Answer 18

Squalene synthase uses NADPH to combine 2 FPPs and removes 4 phosphate groups to form squalene (30C)

Question 19

Comment on what happens to squalene due to the absence of phosphate groups

Answer 19

it is hydrophobic and does not dissolve in the cytosol hence it needs an intracellular carrier protein to keep it dissolved in the cytosol

Question 20

Step 10

Answer 20

Squalene monooxygenase with NADPH and oxygen converts squalene to lanosterol, a 30 C cyclic structure

Question 21

How many steps does cholesterol biosynthesis have?

Answer 21

10

Question 22

What happens to lanosterol after it has been produced?

Answer 22

it is converted to cholesterol via a multi-step process by 18+ different enzymes

Question 23

In what 2 forms does cholesterol exist in the plasma and tissues as

Answer 23

• free cholesterol

- cholesteryl ester

Question 24

What is the storage form of cholesterol?

Answer 24

cholesteryl ester

Question 25

In plasma, both forms of cholesterol are transported ………………

Answer 25

in lipoproteins

Question 26

Cholesterol is the precursor of all other ………………… in the body

Answer 26

steroids

Question 27

Give 4 examples of steroids that are formed from cholesterol

Answer 27

1. sex hormones
2. bile acids
3. vitamin D
4. corticosteroids

Question 28

Cholesterol occurs in food from …………….

Answer 28

animal metabolism

Question 29

4 examples of animal products that cholesterol can be obtained from

Answer 29

1. egg yolk
2. meat
3. liver
4. brain

Question 30

What do low-density lipoproteins do with cholesterol?

Answer 30

they transport free cholesterol and cholesteryl ester to many tissues

Question 31

The function of high-density lipoproteins w.r.t cholesterol

Answer 31

they remove free cholesterol and transport them to the liver for elimination unchanged or by conversion to bile acids

Question 32

What is reverse cholesterol transport?

Answer 32

removal of free cholesterol from tissues by HDLs and transportation to the liver for elimination

Question 33

W.r.t to pathology, cholesterol is a main constituent of ……..

Answer 33

gallstones

Question 34

The chief role of cholesterol in pathological processes is

Answer 34

as a factor in the development in atherosclerosis of vital arteries causing coronary, cerebrovascular and peripheral vascular diseases