Lipid Transport Flashcards

1
Q

What classes of lipids are normally found in the blood?

A
  • Triacylglycerols
  • Fatty acids
  • Cholesterol
  • Cholesterol esters
  • Phospholipids
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2
Q

Why must lipids be transported with protein in the plasma?

A

As they are insoluble in water

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3
Q

How are lipids carried in the blood?

A
  • 98% are carried as highly specialised non-covalent assemblies called lipoprotein particles
  • 2% are carried bound non-covalently to albumin
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4
Q

What is the main class of lipid that travels bound to albumin?

A

Fatty acids

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5
Q

Where do the fatty acids bound to albumin come from?

A

They are released from adipose tissue during lipolysis

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6
Q

What are the fatty acids bound to albumin used for?

A

As a fuel by tissues, e.g. muscle

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7
Q

What is the result of the limited carrying capacity of albumin?

A

Blood fatty acid levels do not normally exceed 3mM

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8
Q

Why do plasma lipoproteins have a great significance in medicine?

A

Since disorders in their metabolism are associated with a number of important diseases, e.g. atherosclerosis and coronary artery disease

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9
Q

How do the classes of lipoprotein differ?

A
  • In the lipid being transported
  • In the origins of the lipid
  • In the destination
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10
Q

What are the protein components of plasma lipoprotein particles?

A

Apoproteins

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11
Q

What are the apoproteins involved in structurally?

A

Packaging non-water soluble lipids into soluble form

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12
Q

What allows apoproteins to package non-water soluble lipids into soluble form?

A

They contain hydrophobic regions that interact with lipid molecules, and hydrophilic regions that interact with water

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13
Q

What are apoproteins involved in functionally?

A

May be involved in the action of enzymes or recognition of cell surface receptors

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14
Q

What determines the function of a lipoprotein particle

A

It’s apoprotein composition

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15
Q

Describe the structure of a lipoprotein

A

Sphreical particles that consist of a surface coat (shell), and a hydrophobic core

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16
Q

What does the surface coat of a lipoprotein particle contain?

A
  • Phospholipids
  • Cholestrol
  • Apoproteins
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17
Q

What does the hydrophobic core of a lipoprotein contain?

A

Tryacylglycerol and cholesterol esters

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18
Q

What do lipoproteins require in order to remain stable?

A

Must keep their spherical shape

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19
Q

What is the maintenance of the spherical shape of lipoproteins dependant on?

A

The ratio of core to surface lipids, therefore as lipid from the hydrophobic core is removed, the surface coat must be reduced

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20
Q

Are the components of the surface coat of lipoproteins molecules free to transfer?

A

Many are, but the core components can only be removed by special proteins, e.g. lipases and transfer proteins

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21
Q

What are the types of lipoproteins?

A
  • Chylomicrons
  • VLDL
  • LDL
  • HDL
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22
Q

What is the transport functions of chylomicrons?

A

Transport dietary triacylglycerols from the intestine to tissues such as adipose tissue

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23
Q

What is the transport function of VLDL?

A

Transport of triacylglycerols synthesised in the liver to adipose tissue for storage

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24
Q

What is the transport function of LDL?

A

Transport of cholesterol synthesised in liver to the tissues

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25
Q

What is the transport function of HDL?

A

Transport of excess tissue cholesterol to the liver for disposal as bile salts

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26
Q

What must be done to dietary lipids to allow their absorption?

A

They cannot be absorbed directly, and are hydrolysed in the small intestine by the enzyme pancreatic lipase that release fatty acids and glycerol

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27
Q

What happens to the fatty acids produced by pancreatic lipase in the digestion of dietary lipids?

A

They enter the epithelial cells of the small intestine, where they’re re-esterified back to triacylglycerols using glycerol phosphate from glucose metabolism

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28
Q

What happens to the triacylglycerols produced in the epithelial cells of the small intestines?

A

They are packaged with other dietary lipids, e.g. cholesterol, fat soluble vitamins into chylomicrons

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29
Q

What happens to the chylomicrons containing the TAGs produced in the epithelial cells of the small intestines?

A

They are released from the epithelial cells into the blood stream via the lymphatic system, and carried tissues

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30
Q

What tissues are chylomicrons carried to?

A

Those that express extracellular enzyme lipoprotein lipase, e.g. adipose

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31
Q

What is the action of lipoprotein lipase?

A

It hydrolyses the triacylglycerols to release fatty acids that enter the cell

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32
Q

What happens to the fatty acids entering the cell after being hydrolysed by LPL?

A

They are converted to triacylglycerols for storage

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33
Q

What is lipoprotein lipase responsible for?

A

Removing the core triacylglycerols from lipoproteins such as chylomicrons and VLDLs

34
Q

Where is lipoprotein lipase found?

A

It’s attached to the inner surface of capillaries in tissues such as adipose tissue and muscle

35
Q

What molecule increases the synthesis of lipoprotein lipase?

A

Insulin

36
Q

What is the action of lipoprotein lipase?

A

It hydrolyses triacylglycerols in lipoprotein particles, releasing fatty acids and glycerols

37
Q

What happens to the products of triacylglycerol hydrolysis?

A
  • The tissues take up fatty acids
  • The glycerols go to the liver
38
Q

What restores the stability of lipoproteins?

A

Lecithin:cholesterol acyltransferase (LCAT)

39
Q

How does LCAT restore the stability of lipoproteins?

A

It converts the surface lipid to core lipid

40
Q

What does LCAT convert cholesterol to?

A

Cholesterol ester

41
Q

How does LCAT convert cholesterol to cholesterol ester?

A

Using fatty acid derived from lecithin (phophatidylcholine)

42
Q

What does deficiency of LCAT result in?

A

Unstable lipoproteins of abnormal structure, therefore generally failure of lipid transport. Lipid deposits occur in many tissues, and atherosclerosis is a serious problem

43
Q

How do tissues obbtain the cholesterol they need?

A

From LDL, by the process of receptor-mediated endolytosis

44
Q

What happens in the receptor-mediated endocytosis of LDL particles?

A

LDL particles are taken up by the cell, and the cholesterol is released inside the cell

45
Q

What cells are able to synthesise cholesterol from acetyl-CoA?

A

All apart from erythrocytes

46
Q

Can cells satisfy their cholesterol requirements by biosynthesis?

A

Yes

47
Q

What cells prefer the uptake of pre-formed cholesterol circulating in plasma lipoproteins, compared to biosynthesis?

A

All

48
Q

How do cells obtain preformed cholesterol?

A
  1. Cells requiring cholesterol synthesise LDL receptors that are exposed to the cell surface
  2. The LDL receptor with its bound LDL is then endocytosed by the cell, and subjected to lysosomal digestion
  3. Cholesterol esters are converted to free cholesterol that is released within the cell
  4. The cholesterol can be stored as cholesterol esters, or used by the cell
49
Q

What effect does the endocytosis of pre-formed cholesterol have on cholesterol biosynthesis?

A

It inhibits it, and reduces the synthesis and exposure of LDL receptors. This prevents the cell from accumulating too much cholesterol

50
Q

What are the types of hyperlipoproteinaemias?

A

I-V

51
Q

What is type I hyperlipoproteinaemia?

A

Chylomicrons are found in the fasting plasma

52
Q

Is type I hyperlipoproteinaemia linked to coronary artery disease?

A

No

53
Q

What is type I hyperlipoproteinaemia caused by?

A

Defective lipoprotein lipase

54
Q

What is type IIa hyperlipoproteinaemia?

A

Raised LDL

55
Q

Is type IIa hyperlipoproteinaemia associated with coronary artery disease?

A

Yes, may be severe

56
Q

What is type IIa hyperlipoproteinaemia caused by?

A

Defective LDL receptor

57
Q

What is type IIb hyperlipoproteinaemia?

A

Raised LDL and VLDL

58
Q

Is type IIa hyperlipoproteinaemia associated with coronary artery disease?

A

Yes

59
Q

What is the defect in type IIa hyperlipoproteinaemia?

A

Unknown

60
Q

What is type III hyperlipoproteinaemia?

A

Raised IDL and chylomicron remnants

61
Q

What is type III hyperlipoproteinaemia associated with?

A

Coronary artery disease

62
Q

Is type III hyperlipoproteinaemia associated with coronary artery disease?

A

Yes

63
Q

What is the defect in type III hyperlipoproteinaemia?

A

Defective apoprotein E

64
Q

What is type IV hyperlipoproteinaemia?

A

Raised VLDL

65
Q

Is type IV hyperlipoproteinaemia associated with coronary artery disease?

A

Yes

66
Q

What is the defect in type IV hyperlipoproteinaemia?

A

Unknown

67
Q

What is type V hyperlipoproteinaemia?

A

Raised chylomicrons and VLDL in fasting plasma

68
Q

Is type V hyperlipoproteinaemia associated with coronary artery disease?

A

Yes

69
Q

What is the defect in type V hyperlipoproteinaemia?

A

Unknown

70
Q

What kind of hyperlipoproteinaemia is familial hypercholesterolaemia?

A

Type IIa

71
Q

What is familal hypercholesterolaemia?

A

A condition in which there be absense (when homozygous trait) or deficiency (heterozygous) of functional LDL receptors

72
Q

What is familial hypercholesterolaemia characterised by?

A

Elevated levels of LDL and cholesterol in the plasma

73
Q

How does the course of the disease differ in homozygotes and heterozygotes?

A

Homozygotes develop extensive atherosclerosis early in life, and heterozygotes develop the condition in later life

74
Q

How can hyperlipoproteinaemias be treated?

A
  • Diet and lifestyle modifications
  • Drug therapy
75
Q

What diet and lifestyle changes are made in hyperlipoproteinaemias?

A
  • Increase exercise
  • Aiming to reduce/eliminate cholesterol from the diet
  • Reduce the intake of triacylglycerols, especially those with saturated fatty acids
76
Q

Are diet and lifestyle modifications effective in all patients with hyperlipoproteinaemias?

A

No, in some it will have little effect

77
Q

What drug therapies are used in the treatment of hyperlipoproteinaemias?

A
  • Statins
  • Bile salt sequesterants
78
Q

How do statins reduce plasma cholesterol?

A

They reduce the synthesis of cholesterol in tissues

79
Q

Give an example of a bile salt sequestrant

A

Cholestyramine

80
Q

How do bile salt sequesterants lower cholesterol?

A

By increasing its disposal from the body, by binding to bile salts in the GI tract, preventing them from being reabsorbed into the hepatic-portal circulation, and promoting their loss in faeces