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What is the main purpose of lipoproteins?
To transport hydrophobic lipids through aqueous blood.
What is typically found on the surface of a lipoprotein particle?
Phospholipids and apolipoproteins, with free cholesterol also present.
What is typically carried in the hydrophobic core of a lipoprotein?
Triacylglycerols and cholesteryl esters.
How does protein-to-lipid ratio relate to lipoprotein density?
A higher protein-to-lipid ratio means higher density; more lipid relative to protein means lower density.
Which lipoprotein is the largest and least dense, and what does it primarily transport?
Chylomicron; it transports dietary TAG from the intestine to tissues.
Which apolipoprotein is required for intestinal chylomicron assembly?
ApoB48.
Which particle donates ApoC-II and ApoE to nascent chylomicrons?
HDL.
What does ApoC-II allow a circulating chylomicron to do?
Activate lipoprotein lipase (LPL) so triglycerides can be hydrolyzed.
What is the fate of fatty acids released by LPL from chylomicron TAG?
They are taken up by tissues such as muscle and adipose tissue for oxidation or storage.
What is a chylomicron remnant?
The smaller, cholesterol-enriched particle left after much of the chylomicron's TAG has been removed by LPL.
Which apolipoprotein helps the liver recognize and take up chylomicron remnants?
ApoE.
What does the exogenous lipoprotein pathway transport?
Dietary lipids absorbed by the intestine, mainly as chylomicrons.
Which lipoprotein is secreted by the liver to transport endogenous TAG?
VLDL.
Which major structural apolipoprotein is present on VLDL, IDL, and LDL?
ApoB100.
What happens to VLDL as LPL removes triglycerides?
It becomes smaller and transitions through IDL; further processing can produce LDL.
What are the two major possible fates of IDL?
It can be taken up by the liver or further processed toward LDL.
What is the major lipid cargo of LDL?
Cholesterol, especially cholesteryl esters.
Which apolipoprotein on LDL is recognized by the LDL receptor?
ApoB100.
What is the main job of the LDL receptor?
To mediate cellular uptake/clearance of LDL and thereby help regulate blood LDL cholesterol.
What is receptor-mediated endocytosis?
A cell takes up a receptor-bound particle into the cell in a membrane-derived vesicle.
How does PCSK9 affect LDL receptor availability?
It promotes receptor degradation/reduces recycling, leaving fewer receptors available to clear LDL.
What is the general effect of PCSK9 inhibition on LDL clearance?
It preserves more LDL receptors and increases LDL clearance from blood.
What is reverse cholesterol transport?
The movement of cholesterol from peripheral tissues toward the liver, involving HDL.
What is the role of nascent HDL in peripheral tissues?
It accepts cholesterol and phospholipids exported from cells.
What does ABCA1 contribute to the HDL pathway?
It transfers cholesterol and phospholipids from cells to nascent HDL.
What does LCAT do during HDL maturation?
It esterifies free cholesterol on HDL, allowing cholesteryl esters to move into the particle core.
What does CETP transfer between lipoproteins?
Cholesteryl esters from HDL to other lipoproteins.
What is the difference between LCAT and CETP?
LCAT chemically esterifies free cholesterol on HDL; CETP transfers cholesteryl esters between lipoprotein particles.
Which lipoprotein is the most protein-rich and highest-density class?
HDL.
What is one function of HDL beyond carrying cholesterol?
It serves as a reservoir/donor of apolipoproteins such as ApoC-II and ApoE for other lipoproteins.
What does SR-B1 participate in during cholesterol handling?
It interacts with HDL in cholesterol uptake/exchange, including hepatic uptake.
What is the role of ABCG1 in cholesterol transport?
It helps move cholesterol from cells to more mature HDL particles.
How can macrophage cholesterol handling connect to atherosclerosis?
When cholesterol-rich ApoB-containing particles enter and are retained in artery walls, macrophages can accumulate lipid and contribute to plaque formation.
Why is cumulative exposure to ApoB-containing particles important?
The longer and more extensively these particles circulate and are retained in artery walls, the greater the opportunity for atherosclerotic plaque development.
What distinguishes exogenous from endogenous lipid transport?
Exogenous transport begins with dietary lipids in intestinal chylomicrons; endogenous transport begins with liver-secreted VLDL.
What is the main sequence of the exogenous pathway?
Chylomicron (ApoB48) → acquires ApoC-II/ApoE from HDL → LPL removes TAG → chylomicron remnant → liver uptake via ApoE.
What is the main sequence of the endogenous pathway?
Liver VLDL (ApoB100) → LPL removes TAG → IDL → liver uptake or conversion to LDL → LDL receptor-mediated uptake.
Why are chylomicrons and VLDL both TAG-rich but different?
Chylomicrons carry dietary TAG from the intestine; VLDL carries endogenous TAG exported by the liver.
What is the key difference between ApoB48 and ApoB100?
ApoB48 is the structural apolipoprotein of intestinal chylomicrons; ApoB100 is found on liver-derived VLDL/IDL/LDL and serves as the LDL receptor ligand.
What is the major role of LPL in circulating lipoprotein metabolism?
It hydrolyzes TAG in chylomicrons and VLDL, releasing fatty acids for tissue uptake.
What is the difference between a chylomicron remnant and LDL?
A chylomicron remnant comes from dietary lipid transport and is cleared by the liver with ApoE; LDL is a cholesterol-rich product of VLDL/IDL processing and carries ApoB100.
What does HDL do when it donates ApoC-II to a chylomicron?
It enables the chylomicron to activate LPL and unload TAG-derived fatty acids.
What is the difference between cholesterol efflux and receptor-mediated lipoprotein uptake?
Efflux moves cholesterol out of cells to acceptors such as HDL; receptor-mediated uptake brings an entire lipoprotein particle into a cell.
Which lipoprotein class is the major carrier in reverse cholesterol transport?
HDL.
Which particle is most associated with delivery of cholesterol to peripheral tissues?
LDL.
Why is ApoE important in both chylomicron and VLDL remnant metabolism?
It acts as a recognition signal that helps the liver take up remnant particles.
What happens to the lipoprotein after LPL has removed much of its TAG?
It becomes smaller and relatively richer in cholesterol/cholesteryl esters; the remnant can then be cleared by the liver or further processed depending on the particle.
What does 'atherogenic ApoB-containing particle' refer to conceptually?
A particle carrying ApoB that can enter and be retained in the artery wall, contributing to atherosclerosis.