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structure of lipoproteins

inner hydrophobic core of TAGs and cholesterol esters, and a shell made of amphipathic phospholipids with their fatty acid chains facing in and the polar head groups out, unesterified cholesterol, and apoliproteins


size vs. density for lipoproteins

as size goes up, the density goes down


functions of apoliproteins

providing recognition sites for cell surface receptors, activating enzymes involved in lipoprotein metabolism, structural components of lipoproteins, some are transferred between lipoproteins



made in intestinal mucosal cells. carry dietary TAG, cholesterol, fat soluble vitamins and cholesterol esters to the peripheral tissue.


chylomicron metabolism

1. Apo B48 is loaded with lipid by MTP. Secreted by fusing with plasma membrane.
2. When the chylomicron reaches blood, it gets Apo-E and Apo-C from HDL particles.
3. Lipoprotein lipase is activated by Apo-CII and hydrolyzes TAG, giving off fatty acids or glycerol.
4. When acted on by LPL, the particle decreases in size and increases in density. Apo-C is returned to HDL via a chylomicron remnant.
5. The remnant is taken up by the liver via Apo-E binding and is degraded and recycled.


lipoprotein lipase (LPL)

anti-parallel homodimer. When Apo-CII binds, the N-terminal region supplies the lipid to a lid covering a hydrophobic active site in the C-term domain. The lid moves so the TAG can be degraded


Metabolism of VLDL

1. VLDLs are made in liver. Secreted into blood containing ApoB100
2. Obtain ApoE and ApoCII from HDL. Some TAGs are transferred from VLDL to HDL in exchange for cholesterol esters via CETP.
3. TAG is degraded by LPL. (same way as in chylomicrons)
4. VLDL -> LDL in the blood with IDL or VLDL remnants. Apo E and CII are returned to HDL particles.
5. LDL particle binds a specific receptor on surface of hepatocytes and extra hepatic tissue.



carry lipids from the liver to the peripheral tissue


CETF (cholesterol ester transfer protein)

catalyzes exchange of TAG from VLDL with cholesterol ester from HDL. Higher TAG concentration = higher rate of exchange


ACAT (acyl CoA:cholesterol acyl transferase)

esterifies cholesterol for storage. increased activity due to oversupply of intracellular cholesterol


uptake and degradation of LDL particles

1. LDL receptors are clustered in clathrin coated pits.
2. LDL receptor complex is endocytosed
3. coated vesicle loses clathrin coat and fuses with other vesicles to form endosomes
4. pH of endosomes drops based on ATP dependent proton pumping. This uncouples LDL and receptor. They separate into areas of the compartment for uncoupling receptor and ligand (CURL)
5. receptors are recycled and endosome fuses with lysosome. lysosome hydrolases degrade LDL and release AA, fatty acids, cholesterol, and phospholipids


coordinate regulation of LDL receptor

oversupply of cholesterol diminishes expression of liver LDL receptor. this is coordinated with the decreased expression and increased degradation of HMG CoA reductase


LDL receptor

6 domains.

LDL binding domain. EGF-like and Transducin Beta domain is where pH dependent conformational change occurs that causes LDL release. Cytosolic domain associates with the clathrin coated pit and initiates endocytosis when LDL binds


mutations in LDL receptor

mostly in the ligand binding and EGF precursor domains



formed in blood. serves as circulating supplier of ApoCII and E. takes up cholesterol from peripheral tissues and return it to the liver as cholesterol esters. Esterification done by lecithin:cholesterol acyl transferase (LCAT)


esterification of cholesterol

LCAT is activated by apoAI and transfers fatty acid from c2 of PC cholesterol. This makes cholesterol ester (CE) and lysoPC.


reverse cholesterol transport

transfer of cholesterol from peripheral cells to HDL, from HDL to liver, and to steroidogenic cells for horomone synth. This is the reason for the inverse relationship between plasma HDL concentration and atherosclerosis and the thought that HDL is good cholesterol. efflux of cholesterol from peripheral tissue is catalyzed by ABCA1.


plaque formation in arterial walls

macrophage scavenger receptors (SR-A) bind ligands causing endocytosis of LDL where the lipid or ApoB have been oxidatively damaged. The macrophages consume LDL and become foam cells, which contributes to plaque formation. plaque forms and a cap forms over the roof. this cap thins out and eventually ruptures which exposes cap contents to procoagulents. this leads to thrombus