CR II - Lipoproteins Flashcards
What are three general roles for apoproteins?
Structural role - due to being amphipathic
Enzymatic
Particle recognition
What are the 4 major types of lipoproteins? What is the major lipid in each? What are the relative densities/percentage of protein content?
Chylomicron - triacylglycerol - 1-2% protein, least dense
VLDL - triacylglycerol - 7-10% protein
LDL - cholesterol - 20% protein
HGL - phospholipid - 30-60% protein, most dense
Where does intermediate density lipoprotein (IDL) lie between the normal lipoproteins?
Between VLDL and LDL
What type of modified protein is Lp(a)? What apoprotein does it have bound to it? With what modification?
Modified LDL
B-100 with apoprotein(a) covalently bound to it
What does apoprotein(a) resemble? Why is it different?
Resembles plasminogen with no plasminogen activity, no fibrinolysis activity
What does Lp(a) prevent? What does it interfere with?
Prevents LDL uptake by LDL receptor
Interferes with fibrinolysis by competing with plasminogen, inhibiting tPA-mediated clot lysis
What disease is Lp(a) a risk factor for? Dependent or independent?
Independent risk factor for cardiovascular disease
Do Lp(a) levels respond to dietary treatment? Why or why not?
No because they are genetically determined by derivation from its own gene, LPA
Which lipoprotein only has one copy of B-100 on it?
LDL
What is the function of A-I apoprotein?
Structural, acitvating LCAT
found on HDL and chylomicrons
Which apoprotein is the LPL cofactor?
C-II
Which two apoproteins can bind to the LDL receptor?
B-100 and E
What lipoprotein carries lipids from digestion? Those synthesized by the liver? A reservoir for apoprotiens?
Chylomicrons - digestion
VLDL - synthesized by liver
HDL - reservoir for apoproteins
How do the other lipoproteins besides Chylomicrons, VLDL, and HDL arise?
Intermediates in metabolism of chylomicrons and VLDL
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?
Lecithin cholesterol acyltransferase (LCAT) Synthesized - liver Secreted - plasma Associates with HDL Activated by apoA-1
What transfers the cholesterol ester fom HDL to VLDL, IDL, and LDL? Where is it synthesized and secreted? What does it associated with?
Cholesteryl ester transfer protein (CETP)
Synthesized - liver
Secreted - plasma
Associated with HDL
What is a plasma protein that facilitates transfer of phospholipid from VLDL, IDL, and LDL to HDL? What does this allow?
Phospholipid transfer protein (PLTP)
Shrinkage of chylomicron and VLDL
What does lipoprotein lipase do? Where is it found? Anchored how/to what?
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
Where is LPL not expressed? What is it sysnthesis and transfer to endothelial cells stimulated by?
Not expressed in liver
Synthesis and transfer stimulated by insulin
What are the three tissues where LPL can be found? Which has a large Km? Small Km? Highest concentration of LPL?
Heart - small Km, highest concentration
Adipose tissue - large Km
Skeletal muscle
Which enzyme hydrolyzes both TAG and phospholipids and is found on the sinusoidal surface of liver cells?
Hepatic lipase
Which proteins move cholesterol from the inner leaflet to the outer leaflet? How? Why?
ABCA1 and Gi
ATP hydrolysis of those enzymes
So cholesterol can be given to HDL
What two surface proteins is the LDL receptor specific for?
B-100 and apoE
Which organ is primary in clearing LDL? What two other tissues are important in clearance?
Liver
Adrenal glands and gonads
How does PCSK9 regulate LDL receptors? Where is it made? Where is it secreted?
Internalized LDL receptors with PCSK9 are sent to lysosomes for destruction
Made in liver
Secreted into blood stream
What structures if LRP similar to? Is it significantly affected by intracellular cholesterol? What three tissues is it present in?
LDL receptor
No
Liver, brain, and placenta
What is the purpose of scavenger receptor B1 (SR-B1)? Where is it expressed?
Binds HDL, allowing cholesteryl esters to be transferred from HDL to liver
Expressed mainly in liver
What two apoproteins do chylomicrons accumulate from the blood stream?
apoC and apoE
What is the purposed of apoC-II on chylomicrons
apoC-II is required for LPL activity
What is removed from the chylomicron by LPL?
TAG
What three surface molecules are transferred from chylomicrons to HDL? Which two things are gained from HDL?
Phospholipid, cholesterol, apoproteins (A and C)
apoE, Cholesterol ester - gained by chylomicron
How are chylomicrons cleared from blood?
By liver through LDL and LRP receptors
What is the half-life of chylomicrons? How much lipid is uptaken before the chylomicron gets to the liver?
Less than 1 hour
80%
Where is VLDL synthesized? Secreted?
Liver
Blood
What does VLDL acquire from HDL?
apoE and apoC
What removes TAG from VLDL? In what tissues?
LPL
peripheral tissues
How is VLDL remnant (IDL) removed by the liver? More copies of what on its surface make it easier to remove?
Binds to LDL receptor and internalized
apoE
How is the other 50% of IDL, which isn’t removed directly by the liver, removed?
IDL converted to LDL
What does LDL only contain 1 molecule of?
apoB100
Does LDL have a long plasma half-life?
Yes, several days
What proportion of LDL is cleared by liver? What is other proportion cleared by?
70% liver
30% other tissues
What four apoproteins does HDL get from the liver? What is the only one given by the intestine?
Liver: AI, AII, E, and C
Intestine: AI
What is HDL’s main purpose in circulation?
Act as reservoir for apoproteins
How does HDL aid in reverse cholesterol transport?
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
What is HDL2 a substrate for?
Hepatic lipase
