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Metabolism > Session 4: Lipid Transport > Flashcards

Session 4: Lipid Transport Flashcards

1
Q

Are lipids hydrophilic or hydrophobic?

A

Hydrophobic

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2
Q

How are a majority of lipids transported in the blood?

A

98% of lipids carried as lipoprotein particles

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3
Q

2% of lipids (mostly fatty acids) are carried bound to ___

A

Albumin

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4
Q

Plasma lipid concentration of triacylglycerol (TGs)

A

1.0 mmol/L

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5
Q

Plasma lipid concentration of phospholipids

A

2.5 mmol/L

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6
Q

Plasma lipid concentration of total cholesterol (TC)

A

5.0 mmol/L

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7
Q

Plasma lipid concentration of cholesterol esters

A

3.5 mmol/L

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8
Q

Plasma lipid concentration of free fatty acids

A

0.4 mmol/L

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9
Q

Lipoprotein structure

A

Spherical particles with nonpolar lipids (triglycerides and cholesterol esters) in their core and more polar amphipathic lipids (phospholipids and free cholesterol) at their surface.

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10
Q

What are apolipoproteins?

A

The protein components of lipoproteins

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11
Q

Phospholipid structure

A

Glycerol backbone, 2 fatty acids hydrophobic tails, 1 hydrophilic phosphate polar head

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12
Q

Some conformations of amphipathic lipids in water

A
  • Liposome
  • Micelle
  • Bilayer sheet
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13
Q

Sources of cholesterol

A
  • Dietary intake
  • Synthesis in the liver
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14
Q

Why is cholesterol important?

A
  • Structural component of cell membranes = modulates fluidity
  • Precursor of steroid hormones = cortisol, aldosterone, testosterone, oestrogen (CATO)
  • Precursor of bile acids and vitamin D
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15
Q

How is cholesterol transported around the body in lipoproteins?

A

Cholesterol transported around body in the form of cholesterol esters in some lipoproteins

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16
Q

Examples of peripheral apolipoproteins

A

ApoC and ApoE

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17
Q

Examples of integral apolipoproteins

A

ApoA and ApoB

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18
Q

What are the two main roles of apolipoproteins?

A
  • Structural = packaging water insoluble (hydrophobic) lipids into a soluble form
  • Functional = cofactor for enzymes and ligand for cell-surface receptors
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19
Q

How many major classes of apolipoproteins are there?

A

Six

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20
Q

ApoB is found on what lipoproteins?

A

Chylomicrons, VLDL, IDL, LDL

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21
Q

ApoAI is found on what lipoproteins?

A

HDL

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22
Q

ApoC and ApoE are found on what lipoproteins?

A

Chylomicrons, VLDL, HDL

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23
Q

What are the five distinct classes of lipoprotein particles named according to?

A

Their density

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24
Q

What are the main carriers of TGs?

A

Chylomicron, VLDL

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25
Q

What are the main carriers of cholesterol esters?

A

IDL, LDL, HDL

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26
Q

Lipoprotein diameter is ___ proportional to density

A

inversely

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27
Q

Chylomicrons (largest diameter = 100-1200 nm) are also the ___ dense

A

least

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28
Q

Order the lipoprotein particles from smallest to largest

A

Smallest = HDL (5-15 nm)
LDL (18-28 nm)
IDL (25-30 nm)
VLDL (30-80 nm)
Largest = Chylomicron (100-1200 nm)

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29
Q

Where are chylomicrons formed?

A

Small intestine

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30
Q

What is the function of chylomicrons?

A

Carry dietary TGs from small intestine to peripheral tissues (especially adipose)

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31
Q

Chylomicrons are normally only present in blood how many hours after a meal?

A

4-6 hours

Persistence after 6h is considered a medical problem.

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32
Q

Chylomicron metabolism

A
  • ApoB-48 added to nascent chylomicrons in enterocytes
  • In blood - chylomicrons acquire apoCII and apoE from HDL
  • ApoCII activates lipoprotein lipase (LPL) on peripheral tissue capillary walls (adipose tissue, muscle)
  • ApoE binds hepatocyte receptors and chylomicron remnants taken up by receptor-mediated endocytosis
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33
Q

Chylomicron remnants are taken by the liver via what mechanism?

A

Receptor-mediated endocytosis

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34
Q

What is lipoprotein lipase (LPL)?

A
  • An enzyme that hydrolyzes triacylglycerol in lipoproteins into fatty acids and glycerol
  • Requires ApoC as factor
  • Found attached to peripheral tissue capillary walls
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35
Q

VLDL is formed in the ___

A

liver

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36
Q

What is the function of VLDL?

A

Transports TGs synthesized by liver cells to adipose tissue for storage

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37
Q

VLDL metabolism

A
  • ApoB100 added to VLDL (nascent) - released into blood
  • HDL gives ApoCII and ApoE to VLDL in blood (mature VLDL)
  • VLDL binds lipoprotein lipase (LPL) on muscle and adipose = releases FAs and glycerol
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38
Q

Transition of VLDL to IDL occurs when…

A

VLDL content depletes to 30% - particle becomes a transient IDL

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39
Q

What are the two fates of IDL?

A

1) IDL taken up by liver via apoE and processed by hepatic triglyceride lipase (HTGL)
2) Further processed to form LDL (depletion to 10%)

40
Q

Transition of IDL to LDL occurs when…

A

Depletion to 10%

41
Q

What is the function of LDL?

A

Transports cholesterol to peripheral tissues

42
Q

LDL binds to cells expressing LDL receptor through ___ and is endocytosed

43
Q

In LDL metabolism, high cellular concentration of cholesterol ___ de novo synthesis of cholesterol and LDL receptor expression.

44
Q

Defects in ___ receptor results in elevated blood cholesterol and cardiovascular disease (CVD)

A

LDL receptor

45
Q

Why is LDL more susceptible to oxidative damage?

A

Half life of LDL in blood is much longer than VLDL or IDL - making it more susceptible to oxidative damage

46
Q

Oxidised LDL is taken up by macrophages to form…

A

Foam cells

47
Q

Foam cells contribute to the formation of ___

A

Atherosclerosis

48
Q

How can atherosclerosis cause angina?

A
  • Oxidised LDL recognised and engulfed by macrophages
  • Macrophages become foam cells - these accumulate in tunica intima of blood vessel walls to form fatty streak
  • Fatty streak evolves into atherosclerotic plaque
  • Plaque grows, encroaches on lumen of artery = angina
49
Q

If an atherosclerotic plaque ruptures, what process is initiated?

A

Triggers acute thrombosis (clot formation) by activating platelets and clotting cascade

50
Q

This is dangerous because it can lead to…

A
  • Stroke
  • Myocardial infarction
51
Q

What does HDL transport?

A

HDL transports excess cholesterol from peripheral tissues to the liver (reverse cholesterol transport) for disposal as bile salts

52
Q

Where is HDL synthesised?

A

Liver and intestines

53
Q

HDL metabolism

A
  • HDL initially only has apoAI, this is followed by addition of apoCII and apoE
  • HDL matures by progressively taking up cholesterol from peripheral tissues via ATP-binding cassette transporter (ABCA1)
  • Cholesterol is esterified to cholesterol ester by Lecithin Cholesterol Acyltransferase (LCAT) which is activated by apoAI
  • Cholesterol exchange transfer protein (CETP) transfers some esters to VLDL by exchanging TG
  • Cholesterol taken up from tissues and returned to liver via scavenger receptor class B type 1 (SR-B1) protein
54
Q

What is the fate of excess cholesterol being carried by HDL back to the liver?

A

1) Lysosomal degradation to free cholesterol which is then used to synthesise steroid hormones
2) Lysosomal degradation at the liver to form cholesterol which is disposed of as bile salts

55
Q

Normal cholesterol blood test levels for total cholesterol (TC)

A

5 mmol/L or less

56
Q

Normal cholesterol blood test levels for non HDL-Cholesterol

A

4 mmol/L or less

57
Q

Normal cholesterol blood test levels for LDL-Cholesterol

A

3 mmol/L or less

58
Q

Total cholesterol : HDL-C ratio above ___ is considered high-risk

A

above 6 is considered high-risk

59
Q

Normal cholesterol blood test levels for triglyceride (TG) in fasted sample

60
Q

What is hyperlipoproteinaemia?

A

Raised plasma level of one or more lipoprotein classes caused by over-production of lipoprotein or under-removal.

61
Q

How many classes of hyperlipoproteinaemia are there?

A

Six main classes

62
Q

Type I hyperlipoproteinaemia

A

Chylomicrons in fasting plasma, Defective lipoprotein lipase (LPL)

63
Q

Type IIa hyperlipoproteinaemia

A

Raised LDL, Defective LDL-receptor

64
Q

Type IIb hyperlipoproteinaemia

A

Raised LDL and VLDL

65
Q

Type III hyperlipoproteinaemia

A

Raised IDL and chylomicron remnants, Defective apoE

66
Q

Type IV hyperlipoproteinaemia

A

Raised VLDL

67
Q

Type V hyperlipoproteinaemia

A

Raised chylomicrons and VLDL in fasting plasma

68
Q

Some general causes of hyperlipoproteinaemia

A
  • Defective enzymes e.g., LPL in type I
  • Defective receptors e.g., LDL-receptor in type IIa
  • Defective apoprotein e.g., apoE in type III
69
Q

Clinical signs of hyperlipoproteinaemia (high levels of cholesterol in blood)

A

Xanthelasma, Yellow patches on eyelids
Tendon Xanthoma, Nodules on tendons
Corneal arcus, White circle around the eye - common in older people

70
Q

First approach for treatment of hyperlipoproteinaemia

A

Diet adjustment
- Reduce cholesterol and saturated lipid in diet
- Increase fiber intake
Lifestyle adjustment
- Increase exercise
- Smoking cessation

71
Q

Second approach for treatment of hyperlipoproteinaemia

A

The second approach is used if the first approach does not work. The second approach involves medications.

72
Q

What are statins?

A
  • Reduce cholesterol synthesis by inhibition of Hydroxymethyl glutaryl-CoA reductase enzyme e.g., Simvastatin, Atorvastatin
73
Q

Statins (HMG-CoA Reductase Inhibitors) prescribed for hyperlipoproteinaemia

A

Atorvastatin, Simvastatin

74
Q

What medication is given for hyperlipoproteinaemia that binds bile salts in the GI tract?

75
Q

What medication is given for hyperlipoproteinaemia that binds bile acids in the GI tract?

76
Q

Statins mechanism of action

A

Inhibits HMG-CoA reductase enzyme activity, which decreases cholesterol synthesis

77
Q

Lipoproteins are classified according to their density. Order lipoproteins from lowest to highest density.

A

Chylomicron (lowest density), VLDL, IDL, LDL, HDL (highest density)

78
Q

What apolipoprotein is specific for chylomicrons?

79
Q

What apolipoprotein is specific for VLDL, IDL and LDL?

80
Q

What tissue is the site of chylomicron formation?

A

Small intestine

81
Q

Which one of the following mediates binding of LDL to its receptor on cells of peripheral tissues?

A

b) apoB-100

82
Q

How are fatty acids transported in the blood?

A

Combined with albumin

83
Q

The largest and least dense lipoprotein is…

A

Chylomicron

84
Q

Lipoproteins consist of which of the following?

A

a) All of the above

85
Q

The smallest and most dense lipoprotein is…

86
Q

The surface of lipoproteins contains which of the following components?

A

c) Phospholipid heads, apoproteins, nonesterified cholesterol

87
Q

What enzyme do statins act on in order to reduce cholesterol synthesis in the body?

A

HMG-CoA reductase

88
Q

Unlike chylomicrons, nascent VLDL directly enters the blood where it obtains apoCII and apoE from circulating HDL. True or false?

89
Q

VLDL is synthesised in the liver and then released to the blood where it is processed to IDL and LDL. True or false?

90
Q

Via what transporting protein does HDL progressively take up cholesterol from peripheral tissues?

A

ATP-binding cassette transporter (ABCA1)

91
Q

Via what enzyme is cholesterol esterified within HDL?

A

Lecithin Cholesterol Acyltransferase (LCAT)

92
Q

Via what transfer protein does HDL transfer some of its esters to VLDL by exchanging TG?

A

Cholesterol exchange transfer protein (CETP)

93
Q

Excess cholesterol taken up from peripheral tissues by HDL is returned to the liver via what protein?

A

Scavenger receptor class B type 1 (SR-B1) protein

94
Q

Which lipoprotein class transports TGs?

A

Chylomicrons, VLDL

95
Q

Which lipoprotein class transports cholesterol esters?

A

IDL, LDL, HDL

Metabolism (15 decks)

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