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ESA2 - Metabolism, Endocrinology and Haematology > Lipid Transport > Flashcards

Lipid Transport Flashcards

1
Q

Why can’t lipids be transported in the blood as they are?

A

Insoluble in water - have to be bound to carriers

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2
Q

How are most lipids carried in the blood?

A

As lipoprotein particles consisting of phospholipid, cholesterol, proteins and TAG

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3
Q

What is the range of concentration of total lipids in the blood?

A

4000-8500 mg/L

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4
Q

How are phospholipids classified?

A

According to their polar head group

Eg

Choline - phosphatidylcholine
Inositol - phosphatidylinositol

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5
Q

Where does the cholesterol in our body come from?

A

Some obtained from diet but most synthesised in liver

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6
Q

What is cholesterol an essential component of?

A

Membranes (modulates fluidity)

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7
Q

What is cholesterol a precursor of?

A

Steroid hormones (eg cortisol, aldosterone, testosterone, oestrogen)

Bile acids

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8
Q

How is cholesterol transported around the body?

A

As cholesterol ester

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9
Q

Which enzymes catalyse the esterification of cholesterol?

A

Lecithin cholesterol acyltransferase (LCAT)

Or

Accl-coenzyme A: cholesterol acyltransferase

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10
Q

What does the cargo of lipoproteins consist of?

A

Triacylglycerol
Cholesterol ester
Fat soluble vitamins

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11
Q

What are the fat soluble vitamins?

A

A D E and K

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12
Q

What are the five classes of lipoproteins?

A

1) Chylomicrons
2) VLDL
3) IDL
4) LDL
5) HDL

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13
Q

What do each of the classes of lipoproteins contain variable contents of?

A

Apoliportein, triglyceride, cholesterol and cholesterol ester

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14
Q

What are the six major classes of apolipoproteins?

A

A B C D E and H

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15
Q

What are the important apolipoproteins?

A

apoB (CLDL, IDL and LDL)

ApoAI (HDL)

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16
Q

Which two positions can apolipoproteins take?

A

Can be integral passing through phospholipid bilayer or peripheral ‘resting’ on top

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17
Q

What are the two roles of apolipoproteins?

A

1) Structural - packaging water insoluble lipid

2) Functional - co-factor for enzymes, ligands for cell surface receptors

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18
Q

Where are chylomicrons loaded and what is added to them before they enter the lymphatic system?

A

Loaded in small intestine and apoB-48 is added

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19
Q

Where do chylomicrons travel to and empty into?

A

Travel to thoracic duct which empties into left subclavian vein

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20
Q

Once in the blood, chylomicrons acquire 2 new apoproteins. What are these?

A

ApoC and apoE

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21
Q

What does apoC do?

A

Binds lipoprotein lipase on adipocytes and muscle. Released fatty acids enter cells depleting chylomicrons of their fat concentration.

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22
Q

When does apoC dissociate?

A

When triglyceride reduced to about 20% - leaving the chylomicron as a chylomicron remnant

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23
Q

Where do chylomicron remnants return?

A

Liver

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24
Q

How is the chylomicron remnant taken up by hepatocytes?

A

LDL receptor on hepatocytes binds apoE and chylomicron remnant is taken up by receptor mediated endocytosis - lysosomes release remaining contents for use in metabolism

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25
Q

What is lipoprotein lipase?

A

Enzyme that hydrolyses triacylglycerol in lipoproteins

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26
Q

What does lipoprotein lipase require?

A

ApoC-II as a cofactor

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27
Q

Where is lipoprotein lipase found?

A

Attached to surface of endothelial cells in capillaries

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28
Q

VLDL are made in the liver for what purpose?

A

Transporting TAG to other tissues

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29
Q

What is added to VLDL during its formation?

A

ApoB100 and apoC and apoE added from HDL particles in blood

30
Q

What does VLDL bind to?

A

LPL on endothelial cells in muscle and adipose tissue and starts to become depleted of TAG

31
Q

When does VLDL. Dissociate from the LPL complex and return to liver?

A

As triacylglycerol content of VLDL particles drops

32
Q

When does VLDL become a short-lived IDL particle?

A

If content depletes to around 30%

33
Q

When does IDL lose apoC and apoE and become an LDL particle?

A

Upon depletion to around 10%

34
Q

What is the primary function of LDL?

A

To provide cholesterol from liver to peripheral tissues

35
Q

How do peripheral cells taken up LDL?

A

Express LDL receptor and take up LDL via process of receptor mediated endocytosis

36
Q

Why aren’t LDL particles not efficiently cleared by the liver?

A

They do not have apoC and apoE - liver LDL-receptor has a high affinity for apoE

37
Q

Why is LDL more susceptible to oxidative damage?

A

Half life of LDL in blood is much longer than VLDL or IDL

38
Q

How do LDL particles contribute to formation of atherosclerotic plaques?

A

Oxidised LDL taken up by macrophages that can transform to foam cells and contribute to formation of atherosclerotic plaques

39
Q

What cells can lead to atherosclerosis?

A

Foam cells

40
Q

What do cells requiring cholesterol express on plasma membrane?

A

LDL receptors

41
Q

What acts as a ligand for LDL receptors?

A

ApoB-100 on LDL

42
Q

What happens after LDL enters cells by receptor mediated endocytosis?

A

Fuse with lysosomes for digestion to release cholesterol and fatty acids

43
Q

What is LDL receptor expression controlled by?

A

Cholesterol concentration in the cell

44
Q

How can HDL be synthesised?

A

1) Nascent HDL synthesised by liver and intestine (low TAG levels)
2) Can also bud off from chylomicrons and VLDL as they are digested by LPL
3) Free apoA-I can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form nascent-like HDL

45
Q

Where do nascent HDL accumulate phospholipids and cholesterol?

A

From cells lining blood vessels

46
Q

True or False:

Transfer of lipids to HDL requires enzyme activity

A

False

47
Q

How can HDL particles reduce the likelihood of foam cell and atherosclerotic plaque formation?

A

HDL have ability to remove cholesterol from cholesterol-laden cells and return it to liver

48
Q

What facilitates the transfer of cholesterol to HDL?

A

ABCA1 protein - cholesterol then converted to cholesterol ester by LCAT

49
Q

How do cells requiring additional cholesterol obtain cholesterol from HDL?

A

Utilise scavenger receptor

50
Q

How can HDL exchange cholesterol ester for TAG with VLDL?

A

Via action of cholesterol exchange transfer protein (CETP)

51
Q

What are hyperlipoproteinaemias caused by?

A

Either over-production or under removal

Defects in:
Enzymes
Receptors
Apoproteins

52
Q

What causes type I hyperlipoproteinaemia?

A

Defective lipoprotein lipase

Chylomicrons in fasting plasma (no link with coronary artery disease)

53
Q

What causes type IIa hyperlipoproteinaemia?

A

Defective LDL receptor

Associated with coronary artery disease

54
Q

What causes type IIb hyperlipoproteinaemia?

A

Defect unknown

Associated with coronary artery disease

55
Q

What causes type III hyperlipoproteinaemia?

A

Defective apoE

Raised IDL and chylomicron remnants

Associated with coronary artery disease

56
Q

What causes type IV hyperlipoproteinaemia?

A

Defect unknown

Associated with coronary artery disease

57
Q

What causes type V hyperlipoproteinaemia?

A

Cause unknown

Raised chylomicrons and VLDL in fasting plasma

Associated with coronary artery disease

58
Q

What are some clinical signs of hypercholesterolaemia?

A

1) High level of cholesterol in blood
2) Xanthelasma
3) Tendon xanthoma
4) Corneal arcus

59
Q

Raised serum levels of what is associated with atherosclerosis?

A

LDL

60
Q

Which layer of blood vessel walls do foam cells accumulate in to form fatty streaks?

A

Intima

61
Q

What is initially used to treat hyperlipoproteinaemias?

A

Dietary changes - reduce cholesterol and saturated lipids in diet and increase fibre intake

Lifestyle changes - increase exercise, stop smoking

62
Q

If diet and lifestyle changes have no effect, what is used to treat hyperlipoproteinaemias?

A

Statins - reduce cholesterol synthesis

Bile salt sequestration - bind bile salts in GI tract and forces liver to produce more bile acids using more cholesterol

63
Q

How do statins reduce cholesterol synthesis?

A

Inhibit HMG-CoA reductase

64
Q

What is an example of a statin?

A

Atorvastatin

65
Q

What is the ideal total cholesterol level?

A

5mmol/L or less

66
Q

What is the ideal non HDL cholesterol level?

A

4 mmol/L or less

67
Q

What is the ideal LDL cholesterol level?

A

3 mmol/L or less

68
Q

What is the ideal HDL cholesterol level?

A

Over 1mmol/L in men

Over 1.2mmol/L in women

69
Q

What ratio of total cholesterol:HDL-C is considered high risk?

A

Ratio above 6 - the lower the ratio the better

70
Q

What is the ideal level of triglyceride?

A

< 2mmol/L in a fasted sample

ESA2 - Metabolism, Endocrinology and Haematology (19 decks)

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