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MCD: metabolism > Cholesterol > Flashcards

Flashcards in Cholesterol Deck (46)
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1

What is cholesterol synthesised from?

Acetyl-CoA
- all the requirments are supplied by the liver

2

What are the three main parts of cholesterol biosynthesis?

- 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).

3

What steroid hormone precursor is derived from cholesterol?

Pregnenolone – gives rise to all 5 types of steroid hormone

4

What Vitamin is synthesised from cholesterol?

Vitamin D

5

What breakdown products of cholesterol are used as bile salts?

Taurocholate and Glycocholate

6

Describe the role of cholesterol in signalling.

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

7

What do the phospholipid monolayers of lipoproteins consist of?

Phospholipids
Cholesterol
Apoproteins

8

What is contained in the core of a lipoprotein?

Cholesteryl ester
Triacylglycerols

9

How are lipoproteins categorised?

Based on density Chylomicrons Very Low Intermediate Low High

10

Where is lipoprotein lipase found and what does it do?

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

11

What is the role of apoproteins in lipoproteins?

Allows the lipoprotein to be recognised by tissues

12

What are the clinical features of familial hypercholesterolaemia?

High risk of severe atherosclerosis and coronary infarction in adolescence

13

What mutation causes FH?

LDLR (LDL receptor)

14

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

Statins are HMG-CoA Reductase inhibitors
Lovastatin – competitively inhibits HMG-CoA Reductase

15

What do Resins and Sequestrants do?

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

16

what is cholestrol?

- cholestrol is a steroid

17

step 1 of biosynthesis of cholestrol?

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

enzyme = B - ketothiolase

18

step 2 of biosynthesis of cholestrol?

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

enzyme = HMG - CoA synthase

19

step 3 of biosynthesis of cholestrol?

3. HMG-CoA is reduced to generate Mevalonate

enzyme = HMG - CoA reductase

20

what regulates the activity of HMG - CoA reductase

- Mevalonate
- cholesterol
- bile salts

21

what happens to the mevalonate?

- undergoes sequential phosphorylation at the hydroxyl groups at positions 3 and 5

- followed by decarboxylation

- to eventually form 3-ISOPENTENYL PYROPHOSPHATE

22

what happens to the isopentenyl pyrophosphate?

it is isomerised to Dimethylallyl pyrophosphate by Isopentenyl Pyrophosphate Isomerase.

23

what happens to the Dimethylallyl pyrophosphate?

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

24

what happens to the geranyl pyrophosphate?

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

15-carbon Farnesyl Pyrophosphate.

25

what happens to the Farnesyl Pyrosphosphate ?

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

26

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

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

27

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

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

28

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

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

29

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

- the precursor is pregenolone

- generated by action of enzyme desmolase

- all five classes of steroid hormones come from pregnenolone

30

how is vit. D synthesised from cholestrol?

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

-----> with hydroxylation
calcitrol