Lipoproteins Flashcards
Chylomicron
formed in the intestines
Main lipid: TAG
Apoproteins: B-48 (A,C,E)
it transports dietary TAG to adipose and other tissues
Chylomicron remnant
main lipid: TAG
Apoproteins: B-48 (A,C,E)
delivers remaining dietary TAG to the liver. exchanged TAG for cholesterol ester from HDL; delivers CE to the liver
VLDL
formed in the liver
main lipid: TAG
apoprotein: B-100 (A,C,E)
transports endogenously synthesized TAG to adipose tissue, skeletal and heart muscle. Exchanges TAG for CE from HDL
IDL
VLDL remnant formed in liver
main lipid: TAG and cholesterol
Apoprotein: B-100, E
Delivers remaining TAG and cholesterol to the liver. exchanges TAG for CE from HDL. Delivers CE to the liver
LDL
formed via processing of IDL in the circulation
Main lipid: cholesterol
Apoprotein: B-100
Delivers cholesterol to the liver and other cells, including steroidogenic cells
HDL
formed in the liver, and sometimes in th intestines
main lipid: cholesterol
Apoprotein: A’s (C, E)
Accepts cholesterol from peripheral cells, esterifies it, and transports CE’s to the liver. Exchanged CE for TAG in VLDL, IDL, chylomicron remnants
Atheroprotective via enzymes such as paraoxonase that inhibit LDL oxidation. Serves as a resovoir for circulating apoproteins (A,C,E) which are transported to other lipoprotein particles.
B-48
Majot LP: Chylomicron
function: chylomicron secretion
B-100
Major LP: VLDL, IDL, LDL
function: Binds LDL recepto, VLDL secretion
A-1
Major LP: HDL
function: activates LCAT (lecithin: cholesterol acyl transferase) and binds HDL receptor
C-II
Major LP: CyM, IDK, VLDL, HDL
function: cofactor that activates LP lipase
E
Major LP: CyM, VLDL, IDL
Function: Cleaance via binding to LRP (LDL receptor associated protein)
Which Apo proteins are cofactors for enzymes?
Apo-CII: lipoprotein lipase
Apo-AI: lecithin: cholesterol acyltransferase
Which apolipoproteins are ligands for extracellular receptors?
ApoE: Binds to LRP
Apo: B-100: Binds to LDL receptor
Apo A-I: binds to HDL receptor
Structural proteins in a lipoprotein particle
Apo B-48: Chylomicrons
Apo B-100: VLDL, IDL, LDL
Apo A-I: HDL
Chylomicron metabolism
1) chylomicrons transport dietary TAG and cholesterol
2) Nascent chylomicrons are synthesized in the intestines along with Apo A-1 and Apo B-48. transported in lymph.
3) Chylomicrons transiently gain ApoE and Apo C-II from HDL in the plasma
4) Apo protein C-II activates lipoprotein lipase (LPL), located on capillary endothelia. LPL catalyzes the conversion of TAGs to free fatty acids an glycerol. Fatty acids are taken up by tissues and metabolized.
5) Chylomicron remnants are removed and destroyed by the liver via receptor mediated endocytosis. This involved ApoE which binds to the LDL receptor and LDL related protein.
6) HDL serves as a repository for Apo C-II, A-I, and E
VLDL
transport TAGs and cholesterol that are synthesized endogenously. is the precursor of IDL and LDL
VLDL metabolism
1) VLDL are synthesized in the liver along with Apo B-100. VLDL picks up Apo E and Apo C-II from HDL in the circulation. Apo C-II activated LPL, which catalyzes the conversion of TAGs to fatty acids and glycerol.
2) As VLDL lose TAG and shrink, they are converted to IDL (VLDL remnant)
3) the TAGs that that were cleaved by LPL become free fatty acid and glyverol which are taken up by tissues and metabolized.
4) in the conversion of IDL to LDL Apo C-II and Apo E are transfered to HDL. LDL retains Apo B-100
During VLDL metabolism how is remaining IDL removed from circulation
receptor mediated endocytosis. this involves the LDL receptor (via binding to Apo B-100 and ApoE ) and LRP (via binding to Apo E). LRP is the receptor related protein.
Apo B-100 on LDL binds to the LDL receptor and is endocytosed. LDL receptors can be found on both liver and non liver tissues.
Effect of statins
inhibit HMG-CoA reductase which synthesizes cholesterol
increased LDL receptors
increased cholesterol removal from circulation
Endocytosis of LDL
LDL and Apo B-100 bind to LDL receptor and get endocytosed in clahtrin coated pits. Inside the lysosone they gt degraded into amino acids, cell membrane, steroid hormones, bile acids, and cholesterol.
Excess of cholesterol
activates ACAT to promote storage of hcolesterol esters
inhibits HMG CoA reductatase and prevents cholesterol formation
inhibits the synthesis of new LDL receptors
Receptor independent pathway of cholesterol
at high cholesterol levels LDL receptor on the surface of cells is reduced, but cholesterol can still be taken up through pinocytosis. This is a rarely used pathway that becomes more important when cholesterol levels are high
Artery disease and cholesterol
Cholesterol can be oxidized. Oxidized LDL can be taken up by macrophages. cholesterol filled macrophages become foam cells. Foam cells accumulate, release cytokines and stimulate proliferation of smooth muscle and calcification of plaque.
continued uptake of oxidized LDL leads to coronary artery disease
Smoking increases LDL oxidation
Reverse cholesterol transport to the liver
nonesterified cholesterol is transfered from plasma membranes to lipid poor HDL which becomes HDL 3 (mediated by ABCA-1). additional chol converts it to HDL2. LCAT (acivated by Apo-A1) esterifies cholesterol.
Gets taken to the liver via CETP or scaevenger proteins
CETP
Mediates the transfer of cholesterol esters from HDLs to VLDL, IDL, and chylomicron in exchange for TAG. This produces a lager HDL2. Cholesterol enrinched IDL and chylomicron remnants are taken up by the liver via Apo-E dependent binding to LDL receptor and LRP
How to spherical HDLs get to the liver
They are taken up receptor mediated endocytosis via ApoAI depdendent binding to the scavenger receptor protein BI (SR-BI)
What is the fate of cholesterol that is taken to the liver
converted to bile or repackaged as lipoprotein.
Autoprotective effects of HDL
contains paroxonase which inhibits LDL oxidation in the intima of blood vessels
HDL increases NO synthesis by endothelial cells
