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MCD: metabolism > Cholesterol > Flashcards

Cholesterol Flashcards

1
Q

What is cholesterol synthesised from?

A

Acetyl-CoA

- all the requirments are supplied by the liver

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2
Q

What are the three main parts of cholesterol biosynthesis?

A
  • 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).
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3
Q

What steroid hormone precursor is derived from cholesterol?

A

Pregnenolone – gives rise to all 5 types of steroid hormone

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4
Q

What Vitamin is synthesised from cholesterol?

A

Vitamin D

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5
Q

What breakdown products of cholesterol are used as bile salts?

A

Taurocholate and Glycocholate

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6
Q

Describe the role of cholesterol in signalling.

A

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

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7
Q

What do the phospholipid monolayers of lipoproteins consist of?

A

Phospholipids
Cholesterol
Apoproteins

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8
Q

What is contained in the core of a lipoprotein?

A

Cholesteryl ester

Triacylglycerols

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9
Q

How are lipoproteins categorised?

A

Based on density Chylomicrons Very Low Intermediate Low High

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10
Q

Where is lipoprotein lipase found and what does it do?

A

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

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11
Q

What is the role of apoproteins in lipoproteins?

A

Allows the lipoprotein to be recognised by tissues

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12
Q

What are the clinical features of familial hypercholesterolaemia?

A

High risk of severe atherosclerosis and coronary infarction in adolescence

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13
Q

What mutation causes FH?

A

LDLR (LDL receptor)

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14
Q

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

A

Statins are HMG-CoA Reductase inhibitors

Lovastatin – competitively inhibits HMG-CoA Reductase

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15
Q

What do Resins and Sequestrants do?

A

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

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16
Q

what is cholestrol?

A
  • cholestrol is a steroid
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17
Q

step 1 of biosynthesis of cholestrol?

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

enzyme = B - ketothiolase

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18
Q

step 2 of biosynthesis of cholestrol?

A
  1. Condensation of another Acetyl-CoA molecule to form HMG-CoA

enzyme = HMG - CoA synthase

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19
Q

step 3 of biosynthesis of cholestrol?

A
  1. HMG-CoA is reduced to generate Mevalonate

enzyme = HMG - CoA reductase

20
Q

what regulates the activity of HMG - CoA reductase

A
  • Mevalonate
  • cholesterol
  • bile salts
21
Q

what happens to the mevalonate?

A
  • undergoes sequential phosphorylation at the hydroxyl groups at positions 3 and 5
  • followed by decarboxylation
  • to eventually form 3-ISOPENTENYL PYROPHOSPHATE
22
Q

what happens to the isopentenyl pyrophosphate?

A

it is isomerised to Dimethylallyl pyrophosphate by Isopentenyl Pyrophosphate Isomerase.

23
Q

what happens to the Dimethylallyl pyrophosphate?

A

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

24
Q

what happens to the geranyl pyrophosphate?

A

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

15-carbon Farnesyl Pyrophosphate.

25
Q

what happens to the Farnesyl Pyrosphosphate ?

A

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

26
Q

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

A

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

27
Q

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

A
  • Squalene epoxide lanosterol-cyclase catalyses the formation of Lanosterol.
28
Q

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

A

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
Q

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

A
  • the precursor is pregenolone
  • generated by action of enzyme desmolase
  • all five classes of steroid hormones come from pregnenolone
30
Q

how is vit. D synthesised from cholestrol?

A

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

—–> with hydroxylation
calcitrol

31
Q

how are bile salts synthesised from cholestrol?

A
32
Q

what is the structure of a lipoprotein?

A
  • 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.
33
Q

how is the cholesteryl ester synthesised?

what is the purpose of its synthesis?

A
  • 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
34
Q

how else might cholesterol esters be made?

A

• 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
35
Q

how are lipoproteins categorised?

A

by their density

  • each has a varying apoprotien content which allows them to be recognised by different cell types
36
Q

how are fats absorbed and where do they travel to?

A

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.

37
Q

where is lipoprotein lipase?

A

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

38
Q

what does lipoprotein lipase do?

A

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

39
Q

what activated lipoprotein lipase?

A

Apoprotein C-II on the chylomicron

40
Q

what happens to heterozygous people with Familial Hypercholesterolaemia?

A
  • cholesterol levels that are 2-3 times higher than in normal people.
41
Q

what happens to homozygous people with Familial Hypercholesterolaemia?

A
  • cholesterol levels are 5 times higher than normal people.

- severe atherosclerosis and coronary infarction

42
Q

what is the function of the LDLRs ?

A

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

43
Q

mutation in what gives FAMILIAL HYPERCHOLESTEROLAEMIA

?

A

mutation in the LDLR gene

44
Q

different classes of LDLR mutations?

A

means that there are different results to the LDLR

45
Q

how to control Hypercholesterolaemia?

A

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

46
Q

what are resins?

A

• These bind bile acid-cholesterol complexes preventing their reabsorption by the intestine.

this means LDL goes down and HDL goes up

MCD: metabolism (9 decks)

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