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Metabolism > 7. Cholesterol > Flashcards

7. Cholesterol Flashcards

1
Q

Cholesterol

A

Steroid
Alters membrane stiffness depending on temperature and nature of membrane
Changes interactions with cytoskeleton

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2
Q

Where is cholesterol synthesised and what from?

A

Liver

From Acetyl-CoA

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3
Q

What are the 3 main parts of cholesterol biosynthesis?

A

Synthesis of isopentyl pyrophosphate from acetyl-CoA
Condensation of 6 molecules of isopentyl pyrophosphate to form squalene
Cyclisation and demethylation of squalene by mono-oxygenates to give cholesterol

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4
Q

What steroid hormone precursor is derived from cholesterol and what enzyme creates this?

A

Pregnenolone

Enzyme: Desmolase

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5
Q

What Vitamin is synthesised from cholesterol?

A

Vitamin D

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6
Q

Where are bile salts generated and stored?

A

Generated in Liver

Stored in Gallbladder

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7
Q

Where do bile salts pass during digestion and what do they do?

A

From bile duct into intestine

Emulsify fats in intestine, aiding digestion and absorption of fats and fat-soluble vitamins (A, D, E, K)

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8
Q

What do bile salts have and what happens when they form micelles?

A

Hydrophobic face and a hydrophilic face.
When they form micelles, their hydrophilic faces face away from triacylglycerols (TAGs) and their hydrophobic faces point towards TAGs.

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9
Q

What does a lack of bile salts result in?

A

Passage of fat through the gut undigested and unabsorbed causing steatorrhea (fatty stool).

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10
Q

What are the major breakdown products of cholesterol?

A

Bile salts

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11
Q

What breakdown products of cholesterol are used as bile salts?

A

Taurocholate and Glycocholate

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12
Q

What are Lipid rafts?

A

Fluctuating assemblies of cholesterol and sphingolipids within a plasma membrane.

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13
Q

What are Hedgehog signalling proteins (N-Hh) covalently attached to?

A

Cholesterol to limit diffusion within tissue to allow for successful limb formation in embryogenesis

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14
Q

What do Lipid rafts do?

A

Organise processes such as cellular signalling by localising key proteins like cell surface receptors

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15
Q

Why is transportation of lipids difficult and what is the solution to this?

A

Lipids are insoluble in aqueous solutions

SOLUTION: package within lipoproteins

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16
Q

What do the phospholipid monolayers of lipoproteins consist of?

A

Phospholipids
Cholesterol
Apoproteins

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17
Q

What is contained in the core of a lipoprotein?

A

Cholesteryl ester

Triacylglycerols

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18
Q

What do apoproteins on lipoproteins allow?

A

Particle to be recognised by tissue

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19
Q

Where are Cholesterol esters synthesised and what from?

A

In plasma

From cholesterol and acyl chain of phosphatidylcholine (Lecithin)

20
Q

What catalyses the formation of Cholesterol esters?

A

Lecithin cholesterol acyltransferase (LCAT)

21
Q

How does LCAT work?

A

More hydrophobic than cholesterol therefore they pack more tightly into the lipoprotein core

22
Q

What can Acyl CoA cholesterol acyltransferase (ACAT) generate?

A

Cholesterol esters from a long chain fatty acyl CoA species.

23
Q

What type of enzyme is ACAT and when does it act on cholesterol?

A

ACAT is an intracellular enzyme

Acts on cholesterol which has been taken in by endocytosis.

24
Q

How are lipoproteins categorised?

A

ACCORDING TO THEIR DENSITY

25
Q

What are the categories of lipoprotein?

A 
Chylomicrons (CM) 
Very Low Density Lipoproteins (VLDL) 
Intermediate Density Lipoproteins (IDL) 
Low Density Lipoproteins (LDL) 
High Density Lipoproteins (HDL)
26
Q

Each type of lipoprotein has a varying apoprotein component, what does this allow?

A

Allows them to be recognised by different cell types

27
Q

When fats are absorbed how are they packaged and where do they travel?

A

Packaged into chylomicrons (CMs)

Travel in lymphatics from intestines to thoracic duct and subclavian vein where they enter blood stream

28
Q

Where is lipoprotein lipase found and what does it do?

A

It is found in capillary endothelial cells

Catalyses hydrolysis of triacylglycerols (in CMs) to glycerol and fatty acids

29
Q

Once lipoprotein lipase has catalysed hydrolysis of triacylglyerols, where are the products used?

A

Fatty acids are used in beta-oxidation

Glycerol is returned to liver for use in gluconeogenesis

30
Q

What plays a key role in activating lipoprotein lipase?

A

Apoprotein C-II of CM

31
Q

What type of cholesterol are HDLs?

A

Good cholesterol

32
Q

What is the function of HDLs?

A

To take cholesterol from peripheral tissues back to liver for use or disposal (reverse cholesterol transport).

33
Q

What do HDLs help to lower?

A

Total serum cholesterol

34
Q

What type of cholesterol are LDLs?

A

Bad cholesterol

35
Q

What does prolonged elevation of LDL levels lead to?

A

Atherosclerosis (hardening of the arteries)

36
Q

What do LDLs do?

A

Transport cholesterol synthesised in liver to peripheral tissues
> 40% of their weight made up of cholesterol esters.

37
Q

What type of disease is familial hypercholesterolaemia (FH)?

A

Inherited monogenic dominant

38
Q

What are the clinical features of familial hypercholesterolaemia?

A

High risk of severe atherosclerosis and coronary infarction in adolescence

39
Q

Heterozygotes with FH serum cholesterol levels

A

2-3X higher than normal

40
Q

Homozygotes with FH serum cholesterol levels

A

5X higher than normal

41
Q

What mutation causes FH?

A

Mutation of LDLR (LDL receptor)

Can’t take up LDLs

42
Q

Describe Receptor mediated endocytosis of LDL

A

LDLRs receive LDLs and send them to the early endosome
Here, LDLRs are recycled back to plasma membrane
LDLs are transferred to lysosomes where they’re degraded to give free cholesterol

43
Q

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

A

Statins are HMG-CoA Reductase inhibitors
Competitive inhibitors stop/reduce cholesterol production
E.g. Lipitor

44
Q

What do Resins and Sequestrants do?

A

Bind or sequester bile acid-cholesterol complexes preventing their reabsorption by the intestine.
Lowers LDL levels
Raises HDL levels

45
Q

In the biosynthesis of cholesterol, where does synthesis of isopentyl pyrophosphate occur?

A

Cytoplasm

46
Q

In the biosynthesis of cholesterol, where does synthesis of squalene occur?

A

Cytoplasm

47
Q

In the biosynthesis of cholesterol, where does the ultimate synthesis of cholesterol occur?

A

Endoplasmic reticulum

Metabolism (9 decks)

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