Lipoproteins 1 Flashcards
Describe polarity of apolipoprotein.
They are amphipathic
What are 3 things that apolipoproteins provide?
1) Structural stability
2) Mediate cellular uptake
3) regulate enzymes in lipid metabolism
Density is _______ proportional to diameter
Inversely
What is HDLs role with respect to apolipoproteins?
HDL acts as a reservoir of apolipoproteins and it exchanges apolipoproteins with other lipoproteins .
What function does ApoB serve?
Structural Apolipoprotein
VLDL contain ApoB ###?
Chylomicrons contain ApoB###
100
48
What is the relationship between ApoB100 and ApoB48
They are made from the same transcript. ApoB48 is 48% of ApoB100. Example of RNA editing that results in different gene product from same trasncript.
Where are chylomicrons and VLDL metabolized?
In the vascular system b/c they are too large to diffuse out of the vasculature
Apo_____ on Chylomicrons and VLDL is recognized by lipoprotein lipase in the membrane of endothelial cells.
C2
Describe how chylomicrons and VLDL are metabolized.
Circulating –> lipoprotein lipase recognize ApoC2 on liporotein –> binding between ApoC2 and LPL –> LPL degrade lipoprotein and free FA diffuse into tissue and are used for energy or converted bak to TAGs for storage
When Chylomicrons and VLDL are metabolized, the tissue does not take up all the contents of the lipoprotein. What is the name for the remaining lipoprotein?
Remnant
Describe the process of forming a chylomicron remnant.
Chylomicron digested in circulation –> when LPL activity is done chylomicron transfers ApoC2 and ApoE back to HDL to become chylomicron remnant.
Chylomicron remnants taken up by the _____
Liver
_____ is the remnant formed from VLDL
In the formation of this remnant, what apolipoproteins are exchanged?
40-60% of this remnant is taken up by what organ?
IDL
VLDL returns ApoC2 and ApoE back to HDL
Liver
What is the remnant formed from IDL?
Where does this remodeling of IDL occur?
What is this lipoprotein rich in?
What apolipoprotein exchanges happens?
LDL
Liver –> enzyme that acts on IDL is hepatic lipase
Cholesterol esters
IDL transfer ApoE to HDL to become LDL
What 2 apolipoproteins are needed for chylomicron remnant to be recognized by the liver?
ApoB48 and ApoE
What 2 apolipoproteins are needed on LDL in order for it to be taken up by peripheral cells?
ApoE
ApoB-100
Why is IDL and LDL clearance from the plasma slower than VLDL?
Because it has lower amounts of ApoE, which is necessary for both lipoproteins to be recognized by their target tissues (Liver for IDL and peripheral tissues for LDL).
What does the slow clearance of LDL allow it to achieve?
Escapes vasculature and is able to gain access to all tissues and lymphatics except brain (blood/brain barrier)
What is the role of PCSK9?
It binds to the LDL receptor and stimultes the internalization and degradation of the receptor. The receptor is recycled to the plasma membrane by endosomes.
If a person had deficient PCSK9, what would be the result on their blood levels?
What if they had too much PCSK9?
Low PCSK9 –> low LDL receptor recycling –> Hypocholesterolemia
Hypercholesterolemia
How are antibodies used to interact with PCSK9 to treat hypercholesterolemia?
They bind to PCSK9 and block its activity –> similar to low levels of recycling –> reduces cholesterol in blood.
What is reverse cholesterol transport?
The transport of cholesterol back to the liver from the periphery. This process is mediated by HDL.
What effect does the reverse cholesterol transport system have on cholesterol synthesis?
Most of cholesterol is made in the liver. Cholesterol acts as inhibitor of its own production via regulation of HMGcoA reductase –> more cholesterol from periphery coming to liver reduces production of cholesterol by liver.
What effect does reverse cholesterol transport have on LDL levels?
If levels of cholesterol in cells decreases b/c it is being sent back to the liver, those cells will upregulate expression of their LDL receptors to get more cholesterol into the cells. As such, LDL levels will decrease because the cells need more cholesterol.
Describe the means by which HDL delivers cholesterol to peripheral cells via selective cholesterol uptake.
HDL delivers cholesterol to liver and steroidgenic tissues directly by binding to SR-BI receptor. This transfer is not dependent on internalization of receptor/lipoprotein compelx and subsequent internal degradation. HDL just releases cholesterol esters to cell and releases without changing HDL levels in blood.
