Lipid Transport Flashcards Preview

Z OLD ESA 1- Metabolism > Lipid Transport > Flashcards

Flashcards in Lipid Transport Deck (136):
1

What is the problem for lipid transport in blood?

They are hydrophobic molecules that are insoluble in water

2

How are lipids transported in blood?

Bound to carriers

3

What percentage of lipids are carried in blood bound to albumin?

~2%

4

What type of lipids predominate in those carried by albumin?

Fatty acids

5

What is the problem with carrying lipids bound to albumin?

It has a limited capacity

6

What is the capacity of carrying lipids bound to albumin?

~3mmol/L

7

How are ~98% of lipids carried?

As lipoprotein particles

8

What do lipoprotein particles consist of?

- Phospholipids
- Cholesterol esters 
- Proteins 
- TAG

9

What do the phospholipids in lipoprotein particles act as?

A shell

10

What do phospholipids consist of?

#NAME?

11

Is a phospholipid molecule hydrophilic or hydrophobic?

#NAME?

12

How are phospholipids classified?

According to head group

13

What do phospholipids have between their head and tail?

Phosphate and glycerol

14

What structures do phospholipids form?

- Liposomes 
- Micelle 
- Bilayer sheet

15

What is a liposome?

Sphere with bilayer

16

What is a micelle?

Sphere with single layer

17

Where does cholesterol in the body come from?

#NAME?

18

What is cholesterol used for?

- Essential component of membranes 
- Precursor of steroid hormones 
- Precursor of bile acids

19

Question…

Answer…

20

Why is cholesterol essential for membranes?

Moderates fluidity

21

Give 4 steroid hormones that cholesterol is a precursor for

- Cortisol
- Aldesterone 
- Testosterone 
- Oestrogen

22

How is cholesterol transported around the body?

As cholesterol esters

23

What is required to esterify cholesterol?

Enzymes that add a fatty acid

24

Give 2 enzymes that can produce cholesterol esters?

#NAME?

25

What are lipoproteins?

Lipid carriers

26

Describe the structure of lipoproteins

- Spheres with phospholipid monolayer
- Have intergral apolipoproteins 
- Have peripheral apolipoproteins

27

What does the phospholipid monolayer of lipoproteins contain?

A small amount of cholesterol

28

What is meant by integral?

Pass through the membrane

29

Give 2 examples of integral apolipoproteins

#NAME?

30

Give 2 examples of peripheral apolipoproteins

#NAME?

31

What does the cargo of lipoproteins consist of?

- Triacylglycerols 
- Cholesterol esters 
- Fat soluble vitamins

32

How many distinct classes of lipoproteins are there?

5

33

What are the classes of lipoproteins named according to?

Density

34

What are the 5 classes of lipoproteins?

- Chylomicrons 
- VLDL (very low density lipoproteins)
- IDL (intermediate density lipoproteins)
- LDL (low density lipoproteins)
- HDL (high density lipoproteins)

35

Which of the lipoprotein classes is very short lived?

IDL

36

What does each class of lipoprotein contain?

A variable content of apolipoprotein, triglyceride, cholesterol and cholesterol ester

37

What are the main carriers of fat?

Chylomicrons and VLDL

38

Why are levels of lipoproteins in blood important?

They are of significant clinical importance

39

How are levels of lipoproteins in the blood determined?

Density obtained by flotation ultracentrifugation

40

How is particle diameter related to density?

Inversely proportional

41

What does a higher % of protein in a lipoprotein mean?

More dense

42

When are chylomicrons normally present in the blood?

4-6 hours after a meal

43

What does each class of lipoprotein have?

A particular component of associated proteins- apolipoproteins

44

What are the 6 major classes of apolipoproteins?

- A
- B
- C
- D
- E
- H

45

What are the two most important apolipoproteins?

#NAME?

46

Where is apoB found?

#NAME?

47

Where is apoAI found?

HDL

48

Are apolipoproteins integral or peripheral?

Can be either

49

What are the roles of apolipoproteins?

- Structural 
- Functional

50

What is the structural role of apolipoproteins?

Help keep integrity of lipoproteins in tact

51

What are the functional roles of apolipoproteins?

- Cofactors for enzymes 
- Ligands for cell surface receptors

52

Where are chylomicrons loaded at the beginning of their metabolism?

Small intestine

53

What happens to chylomicrons in the small intestine?

ApoB-48 added

54

What happens to chylomicrons once apoB-48 has been added?

They enter the lymphatic system

55

Where do chylomicrons go once in the lymphatic system?

They travel to the thoracic duct, into the left subclavian vein

56

Why do chylomicrons empty into the left subclavian vein?

It means by avoid the liver the first time round

57

What happens to the chylomicrons once they’ve been emptied into the left subclavian vein?

ApoC and apoE are added once they’re in the blood

58

What does apoC on chylomicrons do?

Binds lipoprotein lipase (LPL) on adipocytes and muscle

59

What is the result of the binding of apoC and LPL?

Released fatty acids enter the cells, depleting the chylomicron of its fat content

60

To what level is the chylomicrons triglyceride level depleted before the next stage?

~20%

61

What happens once the chylomicron triglyceride content has depleted to ~20%?

The apoC dissociates and the chylomicron becomes a chylomicron remnant

62

What happens to chylomicron remnants?

They return to the liver, where the LDL receptor on hepatocytes binds apoE and the chylomicron remnant is taken up by receptor mediated endocytosis. The lysosomes release remaining contents for use in metabolism

63

What is released from the chylomicron remnants by lysosomes?

#NAME?

64

What is lipoprotein lipase?

An enzyme that hydrolyses triacylglycerols in lipoproteins

65

What does LDL require to function?

ApoC-11 as a cofactor

66

Where is LDL found?

Attached to surface of endothelial cells in capillaries

67

What do chylomicrons carry?

- Fat 
- Cholesterol 
- Vitamins

68

Where are VLDLs made?

In the liver

69

What is the purpose of VLDLs?

Transporting triacylglycerols (TAGs) to other tissues

70

When are apolipoproteins added to VLDLs?

#NAME?

71

Where do VLDLs bind to LDL?

On endothelial cells in muscle and adipose tissue

72

What happens when VLDL binds to LDL?

It starts to become depleted of triacylglycerol

73

What happens to the fatty acids released from VLDLs in muscle?

They are taken up and used for energy production

74

What happens to the fatty acids released from VLDLs in adipose tissue?

The fatty acids are used for re-synthesis of triacylglycerol and stored as fat

75

What happens as triacylglycerol content of VLDL particles drops some?

VLDL particles dissociate from the LDL enzyme complex and return to the liver

76

What happens when VLDL content depletes to ~30%?

Particle becomes short-lived IDL particle

77

What happens to IDL particles?

They can be taken up by the liver or rebind to LPL enzyme for further depletion of TAG content

78

What happens to IDL on depletion to ~10%?

IDL loses apoC and apoE, and so becomes a LDL particle

79

Is the cholesterol content of a LDL particle high or low?

High

80

What is the primary function of LDLs?

To provide cholesterol from liver to peripheral tissues

81

What do peripheral tissues express?

LDL receptor

82

How do peripheral cells take up LDL?

Receptor mediated endocytosis

83

Do LDL particles have apoC or apoE?

No

84

What does the lack of apoC and apoE on LDLs mean?

They cannot be effectively cleaved by the liver

85

Why can LDLs not be effectively cleaved by the liver?

Liver LDL-receptor has a high affinity for apoE

86

How does the half life of LDL in the blood differ from that of VLDL or LDL?

It is much longer

87

What is the result of LDLs having a longer half life in the blood?

They are more susceptible to oxidative damage

88

What happens to oxidised LDL?

It is taken up my macrophages, which can transform to foam cells

89

What do foam cells contribute too?

The formation of atherosclerotic plaques

90

What do cells requiring cholesterol express?

LDL receptors on the plasma membrane

91

What acts as a ligand for the LDL receptors?

ApoB-100 on LDL

92

How is the receptor/LDL complex taken into cells?

By endocytes, into endosomes

93

What happens to the endosomes containing receptor/LDL complexes?

They fuse with the lysosome

94

What is the purpose of the fusing of the endosomes containing the receptor/LDL complex with lysosomes?

Digestion to release cholesterol and fatty acids

95

How can LDL-R expression be controlled?

Cholesterol concentration in the cell

96

How can HDL be synthesised?

- Nascent HDL can be synthesised by liver and intestine
- HDL particles can ‘bud off’ from chylomicrons and VLDL as they are digested by LPL
- Free apoA-1 can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form nascent-like HDL

97

How do HDL particles mature?

- Nascent HDL accumulate phospholipid and cholesterol from cells lining blood vessels 
- Hollow core of HDL progressively fills, and particle takes on more globular shape

98

Does transfer of lipids to HDL require enzymes?

No

99

What do HDL particles have the ability to do?

Remove cholesterol from cholesterol-laden cells, and return it to the liver

100

What is the ability of HDL’s to remove cholesterol important for?

Blood vessels

101

Why is the ability of HDL’s to remove cholesterol important for blood vessels?

Reduces the likelihood of foam cell and atherosclerotic plaque formation

102

What facilitates the transfer of cholesterol to HDL?

ABCA1 protein within the cell

103

What happens once HDL has taken up cholesterol?

The cholesterol is then converted to cholesterol ester by LCAT

104

What happens to mature HDL?

It is taken up by the liver by specific receptors

105

What happens when cells require additional cholesterol?

They can utilise the scavenger receptor to obtain cholesterol from HDL

106

What is the scavenger receptor?

SR-B1

107

Why might cells require additional cholesterol?

Steroid hormone synthesis

108

What can HDL exchange cholesterol ester for?

TAG with VLDL

109

How can HDL exchange cholesterol ester for TAG with VLDL?

By action of cholesterol exchange transfer protein (CETP)

110

What is hyperlipoproteinemia?

Raised plasma levels of one of more lipoprotein classes

111

What causes hyperlipoproteinemia?

Either over-production or under-removal

112

What are the 6 main classes of hyperlipoproteinemia?

- I - Chylomicrons in fasting plasma
- IIa 
- IIb 
- III - Raised IDL and chylomicron remnants 
- IV
- V - Raised chylomicrons and VLDL in fasting plasma

113

Which classes of hyperlipoproteinemia are associated with coronary artery disease?

IIa (may be severe), IIb, III, IV, V

114

What causes class I of hyperlipoproteinemia?

Defective lipoprotein lipase

115

What causes class IIa of hyperlipoproteinemia?

Defective LDL receptor

116

What causes class III of hyperlipoproteinemia?

Defective apoprotein (apoE)

117

What are the clinical signs of hyperlipoproteinemia?

- High level of cholesterol in blood 
- Cholesterol deposition in various areas of the body

118

What conditions are caused by cholesterol deposition?

- Xanthelasma 
- Tendon Xanthoma 
- Corneal arcus

119

What is xanthelasma?

Yellow patches on eyelids

120

What is tendon xanthoma?

Nodules on tendons

121

What is corneal arcus?

An obvious white circle around the eye

122

What is a raised serum LDL associated with?

Atherosclerosis

123

Why is raised serum LDL associated with atherosclerosis?

Oxidised LDL is recognised and engulfed by macrophages. Lipid laden macrophages called foam cells accumulate in intima of blood vessel walls to form fatty streak. Fatty streaks can evolve into atherosclerotic plaque, which grows and encroaches on the lumen of artery.

124

What can atherosclerotic plaques cause?

Angina

125

What happens if an atherosclerotic plaque ruptures?

It triggers an acute thrombosis (clot)

126

How does an atherosclerotic plaque rupture trigger a clot?

By activating platelets and clotting cascade

127

What can a thrombosis cause?

#NAME?

128

What is the first approach to treatment of hyperlipoproteinemia?

Changing diet and lifestyle

129

How is diet altered to treat hyperlipoproteinemia?

#NAME?

130

How is lifestyle altered to treat hyperlipoproteinemia?

#NAME?

131

What happens if someones hyperlipoproteinemia doesn’t respond to diet and lifestyle changes?

Drug therapies

132

What drug therapies are used to treat hyperlipoproteinemia?

- Statins 
- Bile salt sequestrants

133

What do statins do?

Reduce cholesterol synthesis by inhibiting HMG-CoA reductase

134

How does the inhibition of HMG-CoA reductase reduce cholesterol levels?

By inhibiting HMG-CoA reductase, HMG-CoA not converted to mevalonate, so melavonate not converted to squalene (in several reactions), so squalene not converted to cholesterol (in many reactions)

135

What do bile salts sequestrants do?

Bind bile salts in GI tract

136

What is the result of bile salts being binded in the GI tract?

It forces the liver to produce more bile acids using more cholesterol