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87 Cards in this Set

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Lipoprotein with the highest number of triacylglycerides?
Lipoprotein with the highest number of protein and phospholipid?
2 Roles of Apoproteins?
1)sollubilize hydrophobic lipids
2) have cell-targeting signals
Is the core high-density of low density in a chylomicron?
Is the protein surface of the chylomicron high or low density?
where are chylomicrons synthesized?
what is the major fat in our diet?
major enzyme that digests dietary triacylgylcerols?
pancreatic lipases
Where does pancreatic lipase hydrolyze triacylglycerol to FFA and 2-Monoacylglycerol?
lumen of the intestine
What two proteins are initially assembled on chylomicrons?
Apo A
Apo B48
Once in the circulation, which proteins does HDL add to the chylomicron?
Apo E
What activates lipoprotein lipase?
What binds lipoprotein lipase to the endothelial surface of the blood capillaries?
Heparin Sulfate Proteoglycans
HOw do FFA travel to the extrahepatic tissues?
What produces chylomicron remnants?
lipoprotein lipase
What does the liver recognize on the surface of chylomicron remnants?
Apo E
How does the liver take up the chylomicron remnant?
Hepatic Lipase
LDL Receptor
What binds to hepatocyte cell surface by Heparin Sulfate Proteoglycans?
Hepatic Lipase- hydrolyzes triacylglycerides more
What does the LDL receptor to with chylomicron remnant?
targets it to the lysosome where it is degraded and cholesterol is released
3 uses for cholesterol once released in the liver
2)bile salts
2)packaged into other lipoproteins
Which proteins do VLDL and IDL have?
Apo E
Apo B-100
Where is VLDL assembled?
what is a major role of VLDL?
to get rid of excess triacylglycerol in liver cells
3 ways excess triacylglycerol accumulates in the liver
2)plasma FFA
3)chylomicron remnants
lipoprotein lipase breaks VLDL into?
(VLDL remnants)
What interacts with Apo E on IDL to make LDL?
Hepatic Lipase
Which lipoprotein has the most cholesteryl esters?
How is IDL formed from VLDL?
a triacylglycerol is removed by lipoprotein lipase
How is LDL formed from IDL?
a triacylglycerol is removed by hepatic lipase
what proteins are on the surface of LDL?
Only Apo B-100
What is a difference between VLDL and chylomicrons?
VLDL already has Apo CII and Apo E on the cell surface. No need to get from HDL
Higher percentage of cholesterol in VLDL or chylomicron?
Fates of IDL
1)LDL receptor- lysosome-free cholesterol
2)Heaptic Lipase- LDL
Roles of LDL
1)transport cholesterol to peripheral tissues
2) regulation of de novo synthesis at these peripheral tissues
How does LDL bind to LDL receptor?
Apo B-100
Why does LDL last longer in the circulation?
The low affinity of the Apo B-100 receptor
What binds to the LDL receptor?
IDL- high affinity
LDL- low affinity
Why is HDL "good cholesterol"?
it removes excess cholesterol from the circulation
Proteins on HDL
Apo A1
Apo C
Apo E
Where does HDL originate?
liver and small intestine
What is the origional/oblong shape of HDL with no hydrophobic core?
nascent/discoidal HDL
What makes cholesterol esters on surface of spherical particle?
LCAT (Lecithin-Cholesterol Acyl Transferase)
What is ABCA-1?
ATP-binding casette transporter
-delivers cholesterol to Apo-A1 forming nascent HDL
how is nascent cholesterol formed?
cholesterol binding to Apo A1
what activates LCAT?
Apo A1
How is LCAT different from ACAT?
ACAT is in the cell, LCAT is in the blood where it circulates with HDL
what transfers a fatty acid into cholesterol in the blood
Lecithin (phosphatidylcholine)
What transfers fatty acids to cholesterol inside cells?
Fatty Acid Acetyl CoA
What removes lysolecithin from the blood?
What happens to cholesterol esters from HDL?
transferred via CETP (cholesterol ester transfer protein) to LDL or VLDL
what provides a substrate for LCAT?
PLTP (Phospholipid Transfer Protein)
What removes cholesterol esters from HDL and transfers them to IDL and LDL?
CETP (Cholesteryl Ester Transfer Protein)
What is the exchange that CETP does?
gives cholesterol ester to other lipoproteins, transfers trigylcerides onto HDL
LCAT in the plasma is preferentially associated with
receptor in the liver and adrenal gland that mediates selective uptake of cholesteryl esters from HDL particles
(Scavenger Receptor B1)
What happens to HDL after it binds to SR-B1?
depleted HDL recirculates into bloodstream to extract more cholesterol from extrahepatic tissues or other lipoprotein particles
Oncw HLS paticle is mature, 2 things can happen
1) CETP- loads IDL with more cholesteryl esters
2) can interact with SR-B1 receptor
Where is the SR-B1 receptor located?
liver and adrenal gland
Where does HDL commonly acquire cholesterol from?
macrophage foam cells
What does PLTP cause HDL to take up?
PHOSPHOLIPIDS and cholesterol
What are the 3 things measured diagnostically for lipid levels
3) plasma triglycerides
FH is a disorder of ....
gene encoding the LDL receptor
What accumulates in the plasma of FH patients?
Two types of depositions of LDL
1)xanthomas (tendons and skin)
2)atheroma (arteries)
inherritance pattern of FH
autosomal dominant
3 characteristics of atherosclerosis
1)accumulation of cholesteryl esters in arterial wall fro macrophage foam cells (filled with chol. esters)
2) smooth muscle proliferation
3) fibrosis
3 things that happen if your body senses enough cholesterol
1) decrease HMG CoA Reductase
2) increase ACAT (storage)
3)decrease LDL receptors
How does LDL bind to the LDL receptor?
Apo B-100
LDL receptor is what kind of protein?
integral membrane protein
where is the LDL receptor synthesized?
on membrane-bound ribosomes in the ER
How does the LDL receptor travel to the Golgi?
vesicular transport
What does the LDL receptor require?
N-linked co-translational glycosylation
Where does the LDL receptor travel from the Golgi?
to the cell surface
LDL receptor assocaites with __ at the cell surface?
clathrin-coated pits
purpose of endosomes
acidified compartments- allows LDL to dissociate from the LDL receptor
What happens in the lysosomes?
proteins degraded to aa
cholesterol released
What two things does SREBP regulate?
HMG CoA Reductase
LDL Receptor Synthesis
Which part of the SREB acts as a transcriptional activator?
N-terminal domain
When are SREBP activated to go into the nucleus and bind to SREs?
at low cholesterol levels
Two functions of the LDL receptor
1) removes IDL (precursor of LDL)
2) takes up LDL directly
What happens to LDL receptors when eat alot of sat fats and cholesterol?
downregulate LDL receptors....increases plasma LDL levels
Treatment for Heterozygote FH
1)Bile acid binding resins
2) HMG CoA reductase inhibitors
3) diet
Two examples of bile acid binding resins
cholestryamine and colestipol
How do bile acid binding resins work?
bind bile acids in intestinal lumen and prevent absorption- increased fecal excretion of bile acids
-body converts more cholesterol to bile acids...liver responds to chol. deficiency by upregulationg production of LDL receptors
How do statins work?
1) inhibit HMG CoA reductase
2) also inhibit VLDL synthesis (precursor of LDL)-
* cell senses chol. decrease and increases LDL receptors and plasma clearance
problem with using bile acid depletion alone?
body not only up regulates LDL receptors, but also increases de novo synthesis of cholesterol- soln is to use in combo with statin
treatment of homozygote FH
1) plasma exchange- LDL apheresis- everything bound to Apo- B100 removed (not HDL)
2) liver transport
3) gene therapy