Biochem Lipoproteins Flashcards
(87 cards)
1
Q
Lipoproteins are ___ water soluble
A
Poorly
*so a transport mechanism is needed
2
Q
General structure of lipoproteins
A
- Completely hydrophobic molecules inside (triacylglycerols and cholesteryl esters)
- Amphipathic molecules form the coat (cholesterol and phospholipids)
3
Q
Proteins associated with lipoproteins are called ___ which play important roles in the metabolism of lipoproteins through____
A
Apoproteins
- enzymatic
- particle recognition for specific receptors
4
Q
Major lipoproteins in order of least to most dense and the major lipid in each.
*less dense=___ protein content
A
- Chylomicron-triacylglycerol
- VLDL-triacylglycerol
- LDL-cholesterol
- HDL-phospholipid
* less
5
Q
The least dense and largest lipoproteins are ___. They contain the most ___ and the least ___
A
Chylomicrons
Triacylglycerols
Protein
6
Q
The most dense and smallest lipoproteins are ___ which contain the most ___ and the least ___
A
HDL
Protein
Lipid
7
Q
Subclasses of HDL
A
- Nascent HDL (pre beta HDL)
- HDL2
- HDL3
8
Q
Lipoprotein remnants:
A
Chylomicron remnants
VLDL remnants
9
Q
Lp(a), lipoprotein (a) is a modified ___
A
LDL
B-100 with apoprotein (a) covalently bound via a disulfide bond
10
Q
Apoprotein(a) structurally resembles ___, but has no ___ activity (___)
A
Plasminogen
Plasminogen
(Plasminogen activation to plasmin, which is fibrinolytic)
11
Q
Lipoprotein(a) prevents \_\_\_. It interferes with \_\_\_ by \_\_\_. Both Lipoprotein(a) and apoprotein(a) inhibit \_\_\_
A
- LDL uptake
- fibrinolysis by competing with authentic plasminogen
- tPA-mediated clot lysis
12
Q
Lipoprotein(a) levels are an independent risk factor for ____ and are ____, and do not respond to ___
A
Cardiovascular disease
Genetically determined
Dietary treatment
13
Q
Apoprotein(a) is derived from what gene? This gene is thought to have evolved from the ___ gene
A
LPA
Plasminogen (PLG)
14
Q
Apoproteins to know:
Lipoproteins involved
Function
A
- A: HDL, chylomicron, structural
- B-48: intestine, chylomicron, structural
- B-100: liver, VLDL, IDL, LDL, Lp(a), structural, binds to LDL receptor
- C-II: chylomicrons, VLDL, HDL, LPL cofactor
- E: chylomicrons, VLDL, HDL, binds to LDL receptor
15
Q
Which apoproteins bind to LDL receptor?
A
B-100
E
16
Q
Which apoproteins are structural?
A
A
B-48
B-100
17
Q
Lipoproteins and their apoproteins:
Chylomicrons
A
A
B-48
C-II
E
18
Q
Lipoproteins and their apoproteins:
VLDL
A
B-100
C-II
E
19
Q
Lipoproteins and their apoproteins:
IDL
A
B-100
E
20
Q
Lipoproteins and their apoproteins:
LDL
A
B-100
21
Q
Lipoproteins and their apoproteins:
HDL
A
A
C-II
E
22
Q
Lipoproteins and their apoproteins:
Lp(a)
A
B-100-apo(a)
23
Q
Apoprotein E has 3 different alleles
A
E2, E3, E4
E3 has a greater affinity for the LDL receptor than E2. E4 has the greatest.
24
Q
E2 allele for apoprotein E is associated with ___ due to ____.
E4 is associated with ___ due to ___
A
- familial dysbetalipoprotenemia due to less efficient clearance of VLDL and chylomicrons
- hypercholesterolemia and CHD due to increased down regulation of the LDL receptor
25
Persons with Apo E4 have an increased incidence of ___
Late onset Alzheimer's disease
26
Function of lipoproteins is ___
| Specifically?
To transport lipid molecules
- chylomicrons carry lipids from digestion
- VLDL carry lipids from liver
- HDL serve as a reservoir of apoproteins and for cholesterol "reverse transport"
27
These lipoproteins arise as intermediates in the metabolism of chylomicrons and VLDL
Chylomicron and VLDL remnants
IDL
LDL
HDL2 and HDL3
28
Chylomicron are formed in ___ from digestion of ____. Lipids are assembled in the ___. Apoproteins are synthesized in ___. Chylomicrons are assembled in ___.
Nascent chylomicrons are secreted into lymph - including what?
```
Intestinal epithelial cells
ER
Rough ER
Golgi
apoA proteins and apoB-48
```
29
When chylomicrons enter the blood stream they accumulate ___ and ___ from the ___
apoC and apoE from circulating HDL
30
ApoC-II is required for ___. ApoC-III is thought to inhibit ____ by ___
LPL activity
| Premature removal of chylomicrons from circulation by inhibiting binding to receptors, such as LDL and LRP
31
LPL removed 80-90% of the ___
Where?
As this is removed chylomicrons become __
What else happens?
Triacylglycerols
- adipose, skeletal muscle, heart
- smaller
- surface molecules are transferred to HDL (cholesterol, apoA, apoC, and phospholipid-requires PLTP)
32
The chylomicron remnant (after LPL removes TAG) gains __ and ___ from HDL. It is then cleared from the blood by __. How?
```
ApoE and Cholesteryl ester
The liver (binds to LDL (B-100/E) receptor due to presence of apoE and binds to LRP)
```
33
Chylomicrons are only present after a meal. The half life is ___. About 80% of the lipid from chylomicrons goes to ___.
Liver uptake of remnants accounts for ___ of the chylomicron lipid
Less than 1 hour
Heart, adipose tissue, and muscle
20% or less
34
LCAT
| Function
Lecithin cholesterol acyltransferase
| -transfers the fatty acid from the sn-2 position of phosphatidylcholine (aka lecithin) to cholesterol
35
LCAT is synthesize in the ___ and secreted into plasma. It becomes associated with ____ and is activated by ___.
Liver
HDL
ApoA-1
36
CETP
| Function
Cholesteryl ester transfer protein
| -facilitated transfer of cholesteryl ester from HDL to VLDL, IDL, and LDL
37
CETP is synthesized in the ___ and secreted into plasma. It becomes associated with ___
Liver
| HDL
38
PLTP
| Function
Phospholipid transfer protein
| -facilitates transfer of phospholipid from VLDL, IDL, LDL, etc. to HDL
39
LPL
Location
Function
Lipoprotein lipase
- anchored non covalently by interaction with heparan sulfate to capillary endothelial cells of adipose, skeletal muscle, and heart muscle
- catalyzes hydrolysis of triacylglycerol to glycerol and 3 NEFA
40
LPL synthesis and the transfer of LPL to the surface of capillary endothelial cells is stimulated by ___.
LPL is NOT expressed where?
Insulin
| Adult liver
41
Relative Km of LPL in different tissues:?Where is the highest concentration of LPL?
Adipose: large
Heart: small
*heart
42
HL
Function
Location
Hepatic lipase
- hydrolyzes TAG and phospholipids
- non covalently bound to heparan sulfate glycoproteins on the sinusoidal surface of liver cells
43
ABCA1 and ABCG1
What are they?
Function?
ATP binding cassette transporters
- cellular plasma membrane proteins
- required for ATP hydrolysis, they move cholesterol from the inner to outer leaflet
44
LDL (B-100/E) receptor
| Where is it found?
-Plasma membrane receptor in clathrin coated pits
45
___ is of primary importance in clearing LDL. other tissues of importance include:
Liver
Adrenal glands
Gonads
46
Binding of LDL to LDL receptors results in ____
-internalization of the LDL and further metabolism of its constituents
47
The proteolysis of the internalized LDL is controlled by ___, which is a protein synthesized in the ___ and secreted into the blood stream. It binds to the receptor and targets it to ____ when it becomes internalized.
In the absence of this protein, what happens to LDL?
PCSK9
Liver
Lysosomes
Recycled into the plasma membrane
48
LRP
Specificity?
Location?
What does it recognize?
LDL receptor related protein
- not as specific as LDL for lipoproteins
- liver, brain, placenta
- apoE
49
Difference in the effect of intracellular cholesterol concentration on LRP vs LDL
Cholesterol concentration in the cell has a significant effect on LDL but not LRP
50
SR-B1
Where?
Function?
Scavenger receptor B1
- liver and other cells
- binds to HDL via apoA-I and cholesteryl esters are transferred from HDL to liver
51
VLDL and LDL are synthesized in the ___ and assembled in the ____. Their apoproteins are synthesized ___.
Liver
Golgi
On the RER
52
In the bloodstream VLDL requires ___ from HDL
apoE
| apoC
53
TAG is removed from VLDL by ___
Action of LPL of peripheral tissues
54
As VLDL becomes smaller, what components are transferred to HDL ?
apoC
Phospholipid
Some TAG in exchange for cholesteryl ester
55
The VLDL ___ may be removed by the liver
Remnant (IDL)
56
IDL binds to ____ and is internalized. Which IDL is more likely internalized?
Requirements?
LDL (B100/E)
- IDL with multiple copies of apoE
- Have to be small enough to have access to liver cell plasma membranes
57
About ___% of the IDL is cleared by the liver. That which is not becomes ___
50
Remodeled to form LDL
-IDL becomes anchored to hepatic lipase and HL hydrolyzes the TAG and phospholipids of the IDL
-apoE is transferred to HDL
58
LDL is rich in ___. It contains ___ as its apoprotein component. It has a ____ plasma half life, unlike chylomicron remnants and VLDL remnants.
- Cholesteryl waters and cholesterol
- only one molecule of apoB100
- long (up to several days)
59
LDL is cleared from the bloodstream by ____. About ___ % is cleared by the liver and the remaining is cleared by ___
```
Receptor mediated internalization
70
-extrahepatic tissues
1. Adrenal gland; LDL receptors
2. Macrophages; Scavenger receptors
```
60
HDL is synthesized in the ____
Liver and intestine
61
What is nascent HDL ?
Pre beta HDL
A disc shaped phospholipid rich particle with apoproteins
-from liver: A-I, A-II, E, and C
-from intestine: only A-I
62
Once in circulation, HDL acquires what?
- cholesterol from other lipoproteins and from cells
- LCAT from plasma
- CETP from plasma
- other apoproteins from other circulating lipoproteins
63
Transfer of cholesterol to HDL from the ___ of the cells plasma membrane is aided by the action of ___
Outer leaflet
| ABCA1
64
In circulation, what is one function of HDL?
- reservoir for the apoproteins needed by nascent chylomicrons and nascent VLDL
- important role in reverse cholesterol transport
65
HDL3 vs HDL2
HDL3 is small, but becomes larger as it acquires more TAG, and becomes HDL2, which is a substrate for HL (which hydrolyzes the excess TAG and phospholipid)
66
HDL3 removes ___, converting it to ___, and then transfers that to ___ and ___ in exchange for ___ and ___
Cholesterol
Cholesteryl ester
IDL and chylomicrons
Phospholipid and TAG
67
___ of the liver binds HDL2 and selectively transfers cholesteryl ester to the liver cell
SR-B1
68
Abetalipoproteinemia
| Cause
- Deficiency of a triglyceride transfer protein in the ER
- liver and intestine are unable to assemble or secrete apoB-containing lipoproteins
- chylomicrons, VLDL, and LDL are essentially absent
69
Abetalipoproteinemia
| Consequences
- Severe fat malabsorption
- accumulation of triglycerides in intestine and liver
- deficiencies of fat soluble vitamins
70
Abetalipoproteinemia
| Untreated patients develop:
- ataxia
- retinitis pigmentosa
- myopathy
71
Abetalipoproteinemia
| Clinical signs respond to treatment with ___
Vitamin E
72
Tangier disease
| Cause
- deficiency of ABCA1
| - cholesterol cannot be transferred from plasma membrane to nascent HDL
73
Tangier disease
| Consequences
- HDL cannot be formed
- decreased LDL (no transfer of CE to VLDL from HDL)
- CE deposits in reticuloendothelial cells, bone marrow, Schwann cells
74
Tangier disease
| Symptoms
- peripheral neuropathy
- hepatosplenomegaly
- lymphadenopathy
75
Tangier disease has a mild tendency for ___
Early atherosclerosis (due to reduced LDL?)
76
Familial hypercholesterolemia
| Cause
Autosomal dominant
- deficiency of LDL receptor
- heterozygotes: 50% reduction in LDL receptors can double the LDL cholesterol!
- homozygotes: rare. No functional LDL receptors
77
Familial hypercholesterolemia
| Consequences
- accelerated CHD
| - xanthomas
78
Familial LCAT deficiency
| Consequences
- block in reverse cholesterol transport
- limited ability of HDL to acquire cholesterol from VLDL or chylomicrons
- elevated blood cholesterol and triglycerides
79
Familial LCAT deficiency
| Symptoms
- free cholesterol accumulates in most tissues
- kidney disease
- corneal clouding
- mild tendency for early atherosclerosis
80
CETP deficiency
| Consequences
- benign
- CE cannot be transferred from HDL to other lipoproteins
- homozygotes may have 4x elevation of HDL cholesterol, while LDL is normal or low
81
In CETP deficiency ___ is still possible
Reverse cholesterol transport
- through transport of CE by SR-B1 receptors of the liver
- or through endocytosis of HDL with multiple copies of apoE
82
CETP deficiency is common in ___
Japan
83
Frederickson classification of hyperlipoproteinemias
| Type I
```
Hyperchylomicronemia
Rare
Huge increase in triglycerides
Cholesterol may be slightly elevated
Not associated with increased atherosclerosis
-caused by deficiency of LPL and apoC-II
-treatment: low fat diet
```
84
Frederickson classification of hyperlipoproteinemias
| Type II
```
Hypercholesterolemia
Common
LDL elevated
-cause: familial hypercholesterolemia
-secondary causes more common: obesity, diabetes
-major risk factor for atherosclerosis
```
85
Frederickson classification of hyperlipoproteinemias
| Type III
Dysbetalipoproteinemia
Rare
Increased triglycerides and cholesterol
-Causes: homozygotes for apoE2 (which won't bind to hepatic apoE receptors). Chylomicron and VLDL remnants accumulate
-symptoms: xanthomas, increased risk of CHD
-treatment: diet
86
Frederickson classification of hyperlipoproteinemias
| Type IV
Hypertriglyceridemia
Common
Increased triglycerides and cholesterol
-causes: obesity, type 2 diabetes, alcoholism, progesterone-rich contraceptives, excess dietary carbs esp. sugars
87
Frederickson classification of hyperlipoproteinemias
| Type V
```
Hyperlipoproteinemia
Rare
Increased triglycerides and cholesterol
-causes: increased chylomicrons and VLDL, uncontrolled diabetes, obesity, kidney disease
-treatment: diet
```
