Cholesterol

Question 1

What is cholesterol synthesised from?

Answer 1

Acetyl-CoA

- all the requirments are supplied by the liver

Question 2

What are the three main parts of cholesterol biosynthesis?

Answer 2

• Generation of isopentyl pyrophosphate from acetyl-CoA this acts as a building block
• Condensation of six molecules of isopentyl pyrophosphate to form squalene (cytoplasm)
• Cyclisation and demethylation of squalene by monooxygenases to give cholesterol (occurs in ER).

Question 3

What steroid hormone precursor is derived from cholesterol?

Answer 3

Pregnenolone – gives rise to all 5 types of steroid hormone

Question 4

What Vitamin is synthesised from cholesterol?

Answer 4

Vitamin D

Question 5

What breakdown products of cholesterol are used as bile salts?

Answer 5

Taurocholate and Glycocholate

Question 6

Describe the role of cholesterol in signalling.

Answer 6

Cholesterol and sphingolipids form lipid rafts that are involved in localising proteins involved in signalling

Question 7

What do the phospholipid monolayers of lipoproteins consist of?

Answer 7

Phospholipids
Cholesterol
Apoproteins

Question 8

What is contained in the core of a lipoprotein?

Answer 8

Cholesteryl ester

Triacylglycerols

Question 9

How are lipoproteins categorised?

Answer 9

Based on density Chylomicrons Very Low Intermediate Low High

Question 10

Where is lipoprotein lipase found and what does it do?

Answer 10

It is found in capillary endothelial cells
Hydrolyses triacylglycerols to glycerol and fatty acids
Fatty acids are then used in beta-oxidation

Question 11

What is the role of apoproteins in lipoproteins?

Answer 11

Allows the lipoprotein to be recognised by tissues

Question 12

What are the clinical features of familial hypercholesterolaemia?

Answer 12

High risk of severe atherosclerosis and coronary infarction in adolescence

Question 13

What mutation causes FH?

Answer 13

LDLR (LDL receptor)

Question 14

How do statins reduce the accumulation of cholesterol? Give an example.

Answer 14

Statins are HMG-CoA Reductase inhibitors

Lovastatin – competitively inhibits HMG-CoA Reductase

Question 15

What do Resins and Sequestrants do?

Answer 15

Hide bile acid-cholesterol complexes and prevents reabsorption by the intestines
Lowers LDL levels
Raises HDL levels

Question 16

what is cholestrol?

Answer 16

• cholestrol is a steroid

Question 17

step 1 of biosynthesis of cholestrol?

Answer 17

1. Condensation of 2 acetyl-CoA molecules to form Acetoacetyl CoA.

enzyme = B - ketothiolase

Question 18

step 2 of biosynthesis of cholestrol?

Answer 18

2. Condensation of another Acetyl-CoA molecule to form HMG-CoA

enzyme = HMG - CoA synthase

Question 19

step 3 of biosynthesis of cholestrol?

Answer 19

3. HMG-CoA is reduced to generate Mevalonate

enzyme = HMG - CoA reductase

Question 20

what regulates the activity of HMG - CoA reductase

Answer 20

• Mevalonate
• cholesterol
• bile salts

Question 21

what happens to the mevalonate?

Answer 21

• undergoes sequential phosphorylation at the hydroxyl groups at positions 3 and 5
• followed by decarboxylation
• to eventually form 3-ISOPENTENYL PYROPHOSPHATE

Question 22

what happens to the isopentenyl pyrophosphate?

Answer 22

it is isomerised to Dimethylallyl pyrophosphate by Isopentenyl Pyrophosphate Isomerase.

Question 23

what happens to the Dimethylallyl pyrophosphate?

Answer 23

this condenses with a unit of Isopentenyl pyrophosphate to form geranyl pyrophosphate

Question 24

what happens to the geranyl pyrophosphate?

Answer 24

Then a third isopentyl pyrophosphate molecule condenses with geranyl pyrophosphate to form

15-carbon Farnesyl Pyrophosphate.

Question 25

what happens to the Farnesyl Pyrosphosphate ?

Answer 25

-two molecules of the farnesyl pyrophosphate condense to make 30 carbon squalene and 2 molecules of pyrophosphate

Question 26

what is the first step as squalene gets cyclised to cholesterol?

Answer 26

Squalene is first reduced in the presence of oxygen and NADPH to form squalene epoxide

Question 27

what is the second step as squalene gets cyclised to cholesterol?

Answer 27

- Squalene epoxide lanosterol-cyclase catalyses the formation of Lanosterol.

Question 28

what is the third step as squalene gets cyclised to cholesterol?

Answer 28

A series of 1,2-methyl group and hybride shifts along the chain of the squalene molecule result in the formation of four rings.

Question 29

what is the precursor derived from cholesterol which makes steroid hormones?

Answer 29

- the precursor is pregenolone - generated by action of enzyme desmolase - all five classes of steroid hormones come from pregnenolone

Question 30

how is vit. D synthesised from cholestrol?

Answer 30

7 - dehydrocholestrol ---> with UV light Pre Vit D 3 -----> vit. D 3 -----> with hydroxylation calcitrol

Question 31

how are bile salts synthesised from cholestrol?

Answer 31

****

Question 32

what is the structure of a lipoprotein?

Answer 32

- Lipoproteins consist of a phospholipid monolayer containing cholesterol and proteins known as apoproteins - Packed in the core of the lipoprotein is cholesteryl ester and triacylglycerols.

Question 33

how is the cholesteryl ester synthesised? what is the purpose of its synthesis?

Answer 33

- Cholesteryl Ester is synthesised in the plasma from cholesterol and the acyl chain of phosphatidylcholine - This is catalysed by lecithin cholesterol acyltransferase (LCAT). - This makes cholesterol esters MORE HYDROPHOBIC than cholesterol and allows them to pack more tightly within the lipoprotein core

Question 34

how else might cholesterol esters be made?

Answer 34

• Acyl CoA cholesterol acyltransferase (ACAT) can generate cholesterol esters from a long chain fatty acyl CoA species. - ACAT is an intracellular enzyme and acts on the cholesterol that has been taken in by endocytosis

Question 35

how are lipoproteins categorised?

Answer 35

by their density - each has a varying apoprotien content which allows them to be recognised by different cell types

Question 36

how are fats absorbed and where do they travel to?

Answer 36

Fats are absorbed and packaged into chylomicrons which travel in the lymphatics from the intestines to the thoracic duct and the subclavian vein where they enter the blood stream.

Question 37

where is lipoprotein lipase?

Answer 37

Located on the capillary endothelial cells which line a variety of tissues

Question 38

what does lipoprotein lipase do?

Answer 38

Catalyses the hydrolysis of the triacylglycerols (in chylomicrons) to GLYCEROL and FATTY ACIDS.

Question 39

what activated lipoprotein lipase?

Answer 39

Apoprotein C-II on the chylomicron

Question 40

what happens to heterozygous people with Familial Hypercholesterolaemia?

Answer 40

- cholesterol levels that are 2-3 times higher than in normal people.

Question 41

what happens to homozygous people with Familial Hypercholesterolaemia?

Answer 41

- cholesterol levels are 5 times higher than normal people. | - severe atherosclerosis and coronary infarction

Question 42

what is the function of the LDLRs ?

Answer 42

• responsible for receiving the LDLs and sending them to the early endosome.

Question 43

mutation in what gives FAMILIAL HYPERCHOLESTEROLAEMIA | ?

Answer 43

mutation in the LDLR gene

Question 44

different classes of LDLR mutations?

Answer 44

means that there are different results to the LDLR

Question 45

how to control Hypercholesterolaemia?

Answer 45

HMG-CoA Reductase Inhibitors • AKA Statins • Lovastatin is a competitive inhibitor of HMG-CoA Reductase

Question 46

what are resins?

Answer 46

• These bind bile acid-cholesterol complexes preventing their reabsorption by the intestine. this means LDL goes down and HDL goes up