CR II - Lipoproteins Flashcards

1
Q

What are three general roles for apoproteins?

A

Structural role - due to being amphipathic
Enzymatic
Particle recognition

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2
Q

What are the 4 major types of lipoproteins? What is the major lipid in each? What are the relative densities/percentage of protein content?

A

Chylomicron - triacylglycerol - 1-2% protein, least dense
VLDL - triacylglycerol - 7-10% protein
LDL - cholesterol - 20% protein
HGL - phospholipid - 30-60% protein, most dense

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3
Q

Where does intermediate density lipoprotein (IDL) lie between the normal lipoproteins?

A

Between VLDL and LDL

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4
Q

What type of modified protein is Lp(a)? What apoprotein does it have bound to it? With what modification?

A

Modified LDL

B-100 with apoprotein(a) covalently bound to it

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5
Q

What does apoprotein(a) resemble? Why is it different?

A

Resembles plasminogen with no plasminogen activity, no fibrinolysis activity

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6
Q

What does Lp(a) prevent? What does it interfere with?

A

Prevents LDL uptake by LDL receptor

Interferes with fibrinolysis by competing with plasminogen, inhibiting tPA-mediated clot lysis

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7
Q

What disease is Lp(a) a risk factor for? Dependent or independent?

A

Independent risk factor for cardiovascular disease

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8
Q

Do Lp(a) levels respond to dietary treatment? Why or why not?

A

No because they are genetically determined by derivation from its own gene, LPA

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9
Q

Which lipoprotein only has one copy of B-100 on it?

A

LDL

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10
Q

What is the function of A-I apoprotein?

A

Structural, acitvating LCAT

found on HDL and chylomicrons

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11
Q

Which apoprotein is the LPL cofactor?

A

C-II

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12
Q

Which two apoproteins can bind to the LDL receptor?

A

B-100 and E

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13
Q

What lipoprotein carries lipids from digestion? Those synthesized by the liver? A reservoir for apoprotiens?

A

Chylomicrons - digestion
VLDL - synthesized by liver
HDL - reservoir for apoproteins

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14
Q

How do the other lipoproteins besides Chylomicrons, VLDL, and HDL arise?

A

Intermediates in metabolism of chylomicrons and VLDL

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15
Q

Which protein transfers the fatty acid from the 2nd position of PC (lecithin) to cholesterol? Where is it synthesized? Secreted? What does it associate with? What is it activated by?

A
Lecithin cholesterol acyltransferase (LCAT)
Synthesized - liver
Secreted - plasma
Associates with HDL
Activated by apoA-1
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16
Q

What transfers the cholesterol ester fom HDL to VLDL, IDL, and LDL? Where is it synthesized and secreted? What does it associated with?

A

Cholesteryl ester transfer protein (CETP)
Synthesized - liver
Secreted - plasma
Associated with HDL

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17
Q

What is a plasma protein that facilitates transfer of phospholipid from VLDL, IDL, and LDL to HDL? What does this allow?

A

Phospholipid transfer protein (PLTP)

Shrinkage of chylomicron and VLDL

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18
Q

What does lipoprotein lipase do? Where is it found? Anchored how/to what?

A

Catalyzes stepwise hydrolysis of triacylglycerol to glycerol and 3 NEFA (non-essential FA)
Found on capillary endothelial cells
Anchored non-covalently by interaction with GPIHBP1

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19
Q

Where is LPL not expressed? What is it sysnthesis and transfer to endothelial cells stimulated by?

A

Not expressed in liver

Synthesis and transfer stimulated by insulin

20
Q

What are the three tissues where LPL can be found? Which has a large Km? Small Km? Highest concentration of LPL?

A

Heart - small Km, highest concentration
Adipose tissue - large Km
Skeletal muscle

21
Q

Which enzyme hydrolyzes both TAG and phospholipids and is found on the sinusoidal surface of liver cells?

A

Hepatic lipase

22
Q

Which proteins move cholesterol from the inner leaflet to the outer leaflet? How? Why?

A

ABCA1 and Gi
ATP hydrolysis of those enzymes
So cholesterol can be given to HDL

23
Q

What two surface proteins is the LDL receptor specific for?

A

B-100 and apoE

24
Q

Which organ is primary in clearing LDL? What two other tissues are important in clearance?

A

Liver

Adrenal glands and gonads

25
Q

How does PCSK9 regulate LDL receptors? Where is it made? Where is it secreted?

A

Internalized LDL receptors with PCSK9 are sent to lysosomes for destruction
Made in liver
Secreted into blood stream

26
Q

What structures if LRP similar to? Is it significantly affected by intracellular cholesterol? What three tissues is it present in?

A

LDL receptor
No
Liver, brain, and placenta

27
Q

What is the purpose of scavenger receptor B1 (SR-B1)? Where is it expressed?

A

Binds HDL, allowing cholesteryl esters to be transferred from HDL to liver
Expressed mainly in liver

28
Q

What two apoproteins do chylomicrons accumulate from the blood stream?

A

apoC and apoE

29
Q

What is the purposed of apoC-II on chylomicrons

A

apoC-II is required for LPL activity

30
Q

What is removed from the chylomicron by LPL?

A

TAG

31
Q

What three surface molecules are transferred from chylomicrons to HDL? Which two things are gained from HDL?

A

Phospholipid, cholesterol, apoproteins (A and C)

apoE, Cholesterol ester - gained by chylomicron

32
Q

How are chylomicrons cleared from blood?

A

By liver through LDL and LRP receptors

33
Q

What is the half-life of chylomicrons? How much lipid is uptaken before the chylomicron gets to the liver?

A

Less than 1 hour

80%

34
Q

Where is VLDL synthesized? Secreted?

A

Liver

Blood

35
Q

What does VLDL acquire from HDL?

A

apoE and apoC

36
Q

What removes TAG from VLDL? In what tissues?

A

LPL

peripheral tissues

37
Q

How is VLDL remnant (IDL) removed by the liver? More copies of what on its surface make it easier to remove?

A

Binds to LDL receptor and internalized

apoE

38
Q

How is the other 50% of IDL, which isn’t removed directly by the liver, removed?

A

IDL converted to LDL

39
Q

What does LDL only contain 1 molecule of?

A

apoB100

40
Q

Does LDL have a long plasma half-life?

A

Yes, several days

41
Q

What proportion of LDL is cleared by liver? What is other proportion cleared by?

A

70% liver

30% other tissues

42
Q

What four apoproteins does HDL get from the liver? What is the only one given by the intestine?

A

Liver: AI, AII, E, and C
Intestine: AI

43
Q

What is HDL’s main purpose in circulation?

A

Act as reservoir for apoproteins

44
Q

How does HDL aid in reverse cholesterol transport?

A

HDL3 (small) lipid poor and expressed LCAT
LCAT removes cholesterol converting it to CE
CE rich HDL3 transfers CE to IDL and chylomicron remnants in exchange for phospholipid and TAG
As it becomes larger, becomes HDL2
HDL2 binds to SR-B1 on liver, transfering CE to liver cell

45
Q

What is HDL2 a substrate for?

A

Hepatic lipase