Metabolism IX: Lipoproteins Flashcards
Lipids are transported in the plasma as _________ that are composed of _________ and _________.
lipoproteins; apolipoproteins; lipids
What are the 4 classes of lipoproteins?
- VLDL
- HDL
- LDL
- IDL
Transports dietary TAG from the intestines to adipose tissue and other tissues (liver, heart, skeletal muscle).
chylomicron
Delivers remaining dietary TAG to liver. Exchanges TAG for CE from HDL, and then delivers CE to liver.
chylomicron remnant
What is the optimal TAG concentration (aka, triglyceride level in the blood)?
less than 150 mg/dL
What is the optimal LDL concentration? (bad cholesterol)
less than 100 mg/dL
What is the optimal HDL concentration? (good cholesterol)
greater than 39 mg/dL
What is an intermediate density lipoprotein (IDL)?
- VLDL remnant formed via processing of VLDL in the circulation
- delivers remaining TAG and cholesterol to liver
- exchanges TAG for CE from HDL, then delivers CE to liver
What is the common apo-protein among VLDLs, IDLs, and LDLs?
B-100
What is the function of VLDLs?
- transport endogenously synthesized TAG to adipose tissue, skeletal muscle, heart muscle
- exchange TAG for CE from HDL
What is the function of LDLs?
deliver cholesterol to liver and other cells, including steroidogenic cells; “bad” cholesterol
What is the function of HDLs?
- accept cholesterol from peripheral cells, esterify it, and transport CEs to liver
- exchange CE for TAG in VLDL, IDL, and chylomicron remnants
- atheroprotective via enzymes (like paraoxonase) that can protect cells against oxidative damage
- serve as reservoir for circulating apoproteins (A, C, E)
What are apoproteins (aka, apolipoproteins)?
protein components that determine the overall structures and metabolism of lipoprotein classes, and dictate interactions with receptor molecules in liver and peripheral tissues
Chylomicrons transport _______ lipids, while VLDLs, IDLs, and LDLs transport _______ lipids.
exogenous (dietary); endogenous (synthesized)
What is the apoprotein associated w/ chylomicrons vs. VLDLs, IDLs, and LDLs?
- CyM: B-48
- VLDL, IDL, LDL: B-100
What is the function of the B-100 apoprotein, and what does mutation cause?
- function=binding LDL receptor and secreting VLDL
- mutation in B-100 is often implicated in familial hypercholesteremia and makes the body unable to clear cholesterol
What are important co-factors for enzymes?
- Apo-CII: activates lipoprotein lipase
- Apo-AI: activates lecithin:cholesterol acyltransferase (LCAT)
Apo E, Apo B-100, and Apo A-1 are ligans for which extracellular receptors:
chylomicron remnant receptor, LDL receptor, and HDL receptor, respectively
Nascent chylomicrons transiently gain which apoproteins from HDL?
Apo E and Apo C-II
HDL serves as a repository for which apoproteins?
Apo C-II and Apo E (and to a lesser extent, Apo A-1)
How/when are VLDLs converted to IDLs?
They are converted to IDLs as they lose TAG and shrink.
In the conversion of IDL–>LDL, what happens to Apo C-II, Apo E, and Apo B-100?
Apo C-II and Apo E are returned back to HDL, while LDL retains Apo B-100 because it is important for receptor-mediated endocytosis.
What is the major pathway by which LDL is removed from the circulation?
It involves the binding of Apo B-100 on LDL to the LDL receptor on a hepatocyte.
Receptor-independent uptake of LDL is accomplished by ______.
macrophages
What does increased cholesterol of the cell lead to?
down-regulation of high-affinity LDL receptors, and receptor-independent uptake of LDL cholesterol (via pinocytosis)
Is receptor-independent LDL uptake a major or minor cellular pathway?
It is normally a minor pathway but becomes more important when LDL cholesterol levels are high. Already having high cellular cholesterol and bringing additional cholesterol in via LDL receptors can be deleterious for the cell.
How is LDL related to coronary artery disease?
- LDL cholesterol can be oxidized by oxidants
- oxidized LDL can be taken up by macrophages via pinocytosis, and macrophages become “foam cells”
- foam cells accumulate and release cytotoxins that stimulate proliferation of smooth muscle cells and calcification of plaques
- continued uptake of oxidized LDL leads to CAD and atherosclerosis
How does HDL serve an atheroprotective effect?
It contains enzymes, like paraoxonase, that inhibit LDL oxidation in the tunica intima of blood vessels. It also increases NO synthesis by endothelial cells, thus vasodilating the vessels and reducing BP.
