Session 4: Lipid Transport Flashcards
(95 cards)
1
Q
Are lipids hydrophilic or hydrophobic?
A
Hydrophobic
2
Q
How are a majority of lipids transported in the blood?
A
98% of lipids carried as lipoprotein particles
3
Q
2% of lipids (mostly fatty acids) are carried bound to ___
A
Albumin
4
Q
Plasma lipid concentration of triacylglycerol (TGs)
A
1.0 mmol/L
5
Q
Plasma lipid concentration of phospholipids
A
2.5 mmol/L
6
Q
Plasma lipid concentration of total cholesterol (TC)
A
5.0 mmol/L
7
Q
Plasma lipid concentration of cholesterol esters
A
3.5 mmol/L
8
Q
Plasma lipid concentration of free fatty acids
A
0.4 mmol/L
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.
10
Q
What are apolipoproteins?
A
The protein components of lipoproteins
11
Q
Phospholipid structure
A
Glycerol backbone, 2 fatty acids hydrophobic tails, 1 hydrophilic phosphate polar head
12
Q
Some conformations of amphipathic lipids in water
A
- Liposome
- Micelle
- Bilayer sheet
13
Q
Sources of cholesterol
A
- Dietary intake
- Synthesis in the liver
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
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
16
Q
Examples of peripheral apolipoproteins
A
ApoC and ApoE
17
Q
Examples of integral apolipoproteins
A
ApoA and ApoB
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
19
Q
How many major classes of apolipoproteins are there?
A
Six
20
Q
ApoB is found on what lipoproteins?
A
Chylomicrons, VLDL, IDL, LDL
21
Q
ApoAI is found on what lipoproteins?
A
HDL
22
Q
ApoC and ApoE are found on what lipoproteins?
A
Chylomicrons, VLDL, HDL
23
Q
What are the five distinct classes of lipoprotein particles named according to?
A
Their density
24
Q
What are the main carriers of TGs?
A
Chylomicron, VLDL
25
What are the main carriers of cholesterol esters?
IDL, LDL, HDL
26
Lipoprotein diameter is ___ proportional to density
inversely
27
Chylomicrons (largest diameter = 100-1200 nm) are also the ___ dense
least
28
Order the lipoprotein particles from smallest to largest
Smallest = HDL (5-15 nm)
LDL (18-28 nm)
IDL (25-30 nm)
VLDL (30-80 nm)
Largest = Chylomicron (100-1200 nm)
29
Where are chylomicrons formed?
Small intestine
30
What is the function of chylomicrons?
Carry **dietary TGs from small intestine to peripheral tissues** (especially adipose)
31
Chylomicrons are normally only present in blood how many hours after a meal?
4-6 hours
## Footnote
Persistence after 6h is considered a medical problem.
32
Chylomicron metabolism
- 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
33
Chylomicron remnants are taken by the liver via what mechanism?
Receptor-mediated endocytosis
34
What is lipoprotein lipase (LPL)?
- An enzyme that hydrolyzes triacylglycerol in lipoproteins into fatty acids and glycerol
- Requires ApoC as factor
- Found attached to peripheral tissue capillary walls
35
VLDL is formed in the ___
liver
36
What is the function of VLDL?
Transports TGs synthesized by liver cells to adipose tissue for storage
37
VLDL metabolism
- 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
38
Transition of VLDL to IDL occurs when...
VLDL content depletes to 30% - particle becomes a transient IDL
39
What are the two fates of IDL?
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
Transition of IDL to LDL occurs when...
Depletion to 10%
41
What is the function of LDL?
Transports cholesterol to peripheral tissues
42
LDL binds to cells expressing LDL receptor through ___ and is endocytosed
apoB-100
43
In LDL metabolism, high cellular concentration of cholesterol ___ de novo synthesis of cholesterol and LDL receptor expression.
decreases
44
Defects in ___ receptor results in elevated blood cholesterol and cardiovascular disease (CVD)
LDL receptor
45
Why is LDL more susceptible to oxidative damage?
Half life of LDL in blood is much longer than VLDL or IDL - making it more susceptible to oxidative damage
46
Oxidised LDL is taken up by macrophages to form...
Foam cells
47
Foam cells contribute to the formation of ___
Atherosclerosis
48
How can atherosclerosis cause angina?
- 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
If an atherosclerotic plaque ruptures, what process is initiated?
Triggers acute thrombosis (clot formation) by activating platelets and clotting cascade
50
This is dangerous because it can lead to...
- Stroke
- Myocardial infarction
51
What does HDL transport?
HDL transports excess cholesterol from peripheral tissues to the liver (reverse cholesterol transport) for disposal as bile salts
52
Where is HDL synthesised?
Liver and intestines
53
HDL metabolism
- 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
What is the fate of excess cholesterol being carried by HDL back to the liver?
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
Normal cholesterol blood test levels for total cholesterol (TC)
5 mmol/L or less
56
Normal cholesterol blood test levels for non HDL-Cholesterol
4 mmol/L or less
57
Normal cholesterol blood test levels for LDL-Cholesterol
3 mmol/L or less
58
Total cholesterol : HDL-C ratio above ___ is considered high-risk
above 6 is considered high-risk
59
Normal cholesterol blood test levels for triglyceride (TG) in fasted sample
<2 mmol/L
60
What is hyperlipoproteinaemia?
Raised plasma level of one or more lipoprotein classes caused by over-production of lipoprotein or under-removal.
61
How many classes of hyperlipoproteinaemia are there?
Six main classes
62
Type I hyperlipoproteinaemia
Chylomicrons in fasting plasma, Defective lipoprotein lipase (LPL)
63
Type IIa hyperlipoproteinaemia
Raised LDL, Defective LDL-receptor
64
Type IIb hyperlipoproteinaemia
Raised LDL and VLDL
65
Type III hyperlipoproteinaemia
Raised IDL and chylomicron remnants, Defective apoE
66
Type IV hyperlipoproteinaemia
Raised VLDL
67
Type V hyperlipoproteinaemia
Raised chylomicrons and VLDL in fasting plasma
68
Some general causes of hyperlipoproteinaemia
- 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
Clinical signs of hyperlipoproteinaemia (high levels of cholesterol in blood)
Xanthelasma, Yellow patches on eyelids
Tendon Xanthoma, Nodules on tendons
Corneal arcus, White circle around the eye - common in older people
70
First approach for treatment of hyperlipoproteinaemia
Diet adjustment
- Reduce cholesterol and saturated lipid in diet
- Increase fiber intake
Lifestyle adjustment
- Increase exercise
- Smoking cessation
71
Second approach for treatment of hyperlipoproteinaemia
The second approach is used if the first approach does not work. The second approach involves medications.
72
What are statins?
- Reduce cholesterol synthesis by inhibition of Hydroxymethyl glutaryl-CoA reductase enzyme e.g., Simvastatin, Atorvastatin
73
Statins (HMG-CoA Reductase Inhibitors) prescribed for hyperlipoproteinaemia
Atorvastatin, Simvastatin
74
What medication is given for hyperlipoproteinaemia that binds bile salts in the GI tract?
Questran
75
What medication is given for hyperlipoproteinaemia that binds bile acids in the GI tract?
Colestid
76
Statins mechanism of action
Inhibits HMG-CoA reductase enzyme activity, which decreases cholesterol synthesis
77
Lipoproteins are classified according to their density. Order lipoproteins from lowest to highest density.
Chylomicron (lowest density), VLDL, IDL, LDL, HDL (highest density)
78
What apolipoprotein is specific for chylomicrons?
apoB-48
79
What apolipoprotein is specific for VLDL, IDL and LDL?
apoB-100
80
What tissue is the site of chylomicron formation?
Small intestine
81
Which one of the following mediates binding of LDL to its receptor on cells of peripheral tissues?
b) apoB-100
82
How are fatty acids transported in the blood?
Combined with albumin
83
The largest and least dense lipoprotein is...
Chylomicron
84
Lipoproteins consist of which of the following?
a) All of the above
85
The smallest and most dense lipoprotein is...
HDL
86
The surface of lipoproteins contains which of the following components?
c) Phospholipid heads, apoproteins, nonesterified cholesterol
87
What enzyme do statins act on in order to reduce cholesterol synthesis in the body?
HMG-CoA reductase
88
Unlike chylomicrons, nascent VLDL directly enters the blood where it obtains apoCII and apoE from circulating HDL. True or false?
True
89
VLDL is synthesised in the liver and then released to the blood where it is processed to IDL and LDL. True or false?
True
90
Via what transporting protein does HDL progressively take up cholesterol from peripheral tissues?
ATP-binding cassette transporter (ABCA1)
91
Via what enzyme is cholesterol esterified within HDL?
Lecithin Cholesterol Acyltransferase (LCAT)
92
Via what transfer protein does HDL transfer some of its esters to VLDL by exchanging TG?
Cholesterol exchange transfer protein (CETP)
93
Excess cholesterol taken up from peripheral tissues by HDL is returned to the liver via what protein?
Scavenger receptor class B type 1 (SR-B1) protein
94
Which lipoprotein class transports TGs?
Chylomicrons, VLDL
95
Which lipoprotein class transports cholesterol esters?
IDL, LDL, HDL
