Lipoproteins Flashcards
What is the purpose of albumin?
Albumin binds free fatty acids in hydrophobic pockets
What is the purpose of lipoproteins ?
The purpose of lipoproteins is to transport the totally nonpolar TAGs and cholesteryl esters
What is special about lipoproteins?
- Lipoproteins are spherical complexes of lipids that interact to the outside with the water phase and transport inside nonpolar lipids
- The outer shell is a phospholipid monolayer which makes only the outside polar and keeps the inside hydrophobic for transport of TAGs and cholesterol esters
- The monolayer contains apolipoproteins and a small amount of free cholesterol
Give a short description of chylomicrons
Chylomicrons are released by the intestinal mucousal cells into the lymph and contain dietary lipids including lipid-soluble vitamins
Give a short description of VLDLs
VLDLs are released by the liver into the blood and contain TAGs and cholesterol esters
Give a short description of LDLs
LDLs are formed in the blood from VLDL and deliver cholesterol esters to cells that need cholesterol.
Give a short description HDLs
HDLs perform the reverse cholesterol transport to the liver and are filled in the blood with cholesterol esters. They also provide apolipoproteins to chylomicrons and VDLD
Contrast the lipoproteins in terms of s8zes
Chylomicrons are the largest and contain mostly TAGs.
VLDLs are TAG-rich and LDLs are cholesterol rich
HDLs are the smallest and rich in app-proteins
How are lipoproteins separated based on density?
Separation by ultra-Centrifugation from very low to high density leads to naming as VLDL, IDL, LDL and HDL
- Chylomicrons are separated without Centrifugation as they float on top of a blood sample
- VLDL (Very low density lipoproteins)
- IDL( intermediate density lipoprotein)
- LDL (low density lipoprotein )
- HDL (high density lipoprotein)
Which lipoprotein has the highest % of TAGs?
Chylomicrons
What does high chylomicrons and VLDL lead to?
Chylomicrons (CM) and VLDL represent the lipoproteins that transport most TAGs in the blood
As increase of CM or VLDL leads to “high TAGs in blood” the TAGs are found inside lipoprotein and are not free in the blood
Which lipoprotein has the highest % of cholesterol?
LDL has the highest % of cholesterol ester and free cholesterol
Explain the metabolism of chylomicrons
- Intestinal mucousal cells secrete nascent TG-rich chylomicrons produced primarily from dietary lipids
- Apo C-II and apo E are transferred from HDL to the nascent CM
- Extracellular lipoprotein lipase, activated by apo C-II, degrades TG in CM
- Apo C-II is returned to HDL
- CM reminants bind to specific receptors on the liver where they are endocytosed
How are chylomicrons formed?
Chylomicrons are formed by intestinal mucousal cells and contain dietary lipidsincluding lipid-soluble vitamins. They are released from the cells into the lymph
What is the function of chylomicrons?
To transport dietary lipids in the blood and provide substrates for lipoprotein lipases which cleave TAGs in lipoproteins
Where are lipoproteins? What do they do?
Lipoproteins are anchored in capillaries of heart, muscle and adipose tissue and they generate free fatty acids, glycerol and lipoprotein that is now smaller in size (a remnant)
The formed chylomicron remnants have the function to deliver the dietary cholesterol esters, lipid-soluble vitamins and some TAGs to the liver.
Some hepatic receptors allow endocytosis into the hepatocytes
Explain the mechanism lipoprotein lipase functioning
- Lipoprotein lipase is anchored in capillariesvog heart, muscle and adipose tissue. LPL cleaves TAGs inside of lipoproteins
- LPL acts in the blood and needs activation by apo C-II which it finds in chylomicrons and VLDL
- The free fatty acids are taken up into the heart and muscle for energy metabolism (beta-oxidation) or into fat cells for storage as TAGs
Explain the metabolism of VLDL
- Liver secretes nascent TG rich very low density lipoprotein particles
- Apo C-II and apo E are transferred from HDL to nascent VLDL
- Extracellular lipoprotein lipase, activated by apo C-II, degrades TG in VLDL
- Apo C-II and apo E are returned to HDL
- LDL binds to specific receptors on extrahepatic tissues and on the liver, where they are endocytosed
Where are VLDL formed?
Formed in hepatocytes and contain TAGs and cholesterol esters
What are some purposes of VLDL?
- One purpose of VLDL release from the liver is to prevent TAG accumulation in hepatocytes and also to provide substrates for lipoprotein lipase. LPL generates fatty acids that are used for energy metabolism in the heart or are stored in fat cells
- Another purpose of VLDL release is to generate eventually LDL which can distribute cholesterol esters to the cells
What is the remnant VLDL after cleavage of some TAGs by LPL?
IDL is the remnant of VLDL after cleavage of some TAGs by LPL. IDL is either taken up into the liver or will be used to form LDL in the blood
LDL deliver cholesterol esters to cells by endocytosis of the LDL-LDL receptor complex. Hepatocytes take up most of the LDL to prevent high blood levels of LDL
How does high cholesterol level affect gene expression?
High level of cholesterol inhibits expression of HMG CoA reductase
Inhibits DNA transcription
Explain the cellular uptake and degradation of LDL
- The LDL receptor in the coated pit binds LDL and both are taken up by endocytosis
- After the clathrin cost is lost an endosome is formed. The pH of the endosome allows the separation of LDL from its receptor and the LDL-receptor can be recycled whereas the LDL is degraded to free cholesterol, free fatty acids and amino acids.
- At high cytosolic free cholesterol levels a reservoir of cholesteryl esters are formed. High free cholester inhibits the gene expressions of HMG CoA reductase and of the LDL-receptor
- A low free hepatic cholesterol level leads to LDL-receptor synthesis. More LDLs bind and are taken up into the liver. This leads to a lower LDL level (cholesterol) in the blood
What can inhibit/activate LDL modification to oxLDL?
Activate- superoxide, nitric oxide, hydrogen peroxide, other oxidants
Inhibit- Vitamin E, ascorbic acid, B-carotene and other antioxidants
Explain oxLDL uptake by macrophages
- Low affinity, non-specific and non regulated scavenger receptors take up modified LDL (oxLDL)
- High affinity receptors specific for LDL become down-regulated when the cell has sufficient cholesterol
oxLDL is not regulated by the LDL receptor
The scavenger receptors in macrophages also uptake of oxLDL and this can lead to “foam” cells that release pro inflammatory mediators
How can high LDL and oxLDL levels be harmful to health?
- Fatty streaks contain smooth muscle cells and macrophages (foam cells) filled with oxLDL
- fibrofatty atheroma shows smooth muscle proliferation, collagen and lipid debris from destroyed foam cells
How can HDLs be beneficial for health?
HDLs prevent or reduce atheroma
HDL is formed as an “empty” phospholipid shell and is filled in the blood with cholesteryl esters and transfers cholesterol away from blood vessels and delivers it to the liver.
What are the functions of HDLs?
HDLs always transport cholesterol from cell membranes back to the liver. -HDL reverse cholesterol transport
Free cholesterol is released into the blood from membranes undergoing turnover and from dying cells
Explain the metabolism of HDLs
HDL functions related to lipoprotein metabolism
- HDLs act as a “reservoir” of specific apolipoproteins which are transferred from HDL to chylomicrons or to VLDL
- HDLs transport cholesterol from plasma membrane turnover to the liver(reverse cholesterol transport as cholesteryl ester)
- HDLs prevent or reduce fatty streak formation in blood vessels
