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55 Cards in this Set
- Front
- Back
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What two organs are key in cholesterol balance?
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liver and the intestines
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What is added to a cholesterol during transport or storage?
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a fatty acid chain to the hydroxyl group
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What is the coat of lipoproteins principally made of?
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phospholipids (hydrophilic) and some apoproteins
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phospholipids are amphipathic, why does this suit the needs of the lipoproteins?
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it is stable with a aqueous environment and a non-polar core
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Besides being amphipathic, what other physical properties do they have that determine their function?
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So, besides stabilizing by being amphipathic, they have binding receptors and enzymes… that help in attachment and activators respectively
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What special function do ApoA (A1)have?
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activate LCAT and receptor binding
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What special function do ApoB have?… b) and what do their lipoproteins do? (B48, B100)
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a) receptor binding…b) 1. their lipoproteins deliver TAGs to muscle and fat tissue… 2. they also remove cholesterol from the body " reverse cholesterol transport"
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What special function do ApoC have? (CII)
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Activates lipoprotein lipase (LPL)
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What special function do ApoE have? (E)
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Receptor binding
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What are the 3 steps in the life of a Apob lipoprotein?
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1) assembly and secretion… 2) intravascular metabolism… 3) receptor mediated removal from blood plasma
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Where would you find the ApoB48 and ApoB100?
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ApoB48=intestines, Apo100=liver
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where is ApoB regulated? And how is it different in the liver versus the intestines and other tissues?
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ApoB mRNA editing… b) liver transcribes entire gene and edits out only intron (B100=100%)… the intestines premature stop codon (B48=48%)
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Which ApoB containing lipoprotein gives rise to LDL?
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ApoB100 = VLDL… thus, it is the the B100 that is giving rise to atherosclerosis
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What role does MTP play in VLDL and CM?
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they introduce TAGs into the growing lipoprotein
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In what state is ApoB being produced?
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fed state… otherwise it is degraded
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Do all Apo stay with a lipoprotein?
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no but ApoBs do… others are exchangeable
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Which Apo must enter ApoB containing lipoproteins (CM) from HDLs? (exchange) Why?
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a) ApoCII… b) it activates the lipoprotein, such that it allows binding to lipoprotein lipase (LPL), thus fatty acids are released from TAGs and enter the cell (muscle or fat)
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After the ApoB lipoprotein (CM) has unloaded its TAG, why does it swap its newly acquired ApoCII for a ApoE with an HDL? Biochemical reason and function
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a) having lost its TAGs, the ApoB lipoprotein is smaller and has more affinity for the ApoE… b) the ApoE targets it for the liver to be recycled.
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What is the general cause for the formation of LDLs?
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they are the product of the less efficient clearance of VLDLs
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What liver cell surface protein does the CM's ApoE bind?
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LRP = (LDL receptor related protein)
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What is the half-life of the process of CM synthesis and breakdown?
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1/2 hour
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How do 50% of the VLDL remnants get cleared from blood plasma?
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an LDL receptor on the liver uptakes the remnant for recycling
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What happens to the other 50% of VLDL remanants?
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some go back to the fat or muscle cell and unload more TAGs… these are called IDLs
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What causes some of the VLDL remnants to become LDLs?
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The remnant binds to a liver surface receptor that is much like the ApoCr (found on Lipoprotein lipase near fat and muscle cells)… it then unload the rest of its TAG and fatty acids and glycerol is taken up by the liver… the remnant becomes more dense (but has a high percentage of cholesterol)... it loses it ApoE receptor due loss of affinity, thus it has not affinity for the LDL receptor
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What is the clearance half-life for VLDL remnants after it loses its ApoE receptor?
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2.5 days
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What type of uptake does the LDL receptor mediate?
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receptor medicated endocytosis
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What happens to the cholesterol taken up by the the LDL?
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The VLDL remanant, after taken up by the LDL, goes to a lysosome, broken down, and the cholesterol is sent to the ER. The ER puts esters on the cholesterol and down regulates cholesterol synthesis.
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How does the cell down regulate cholesterol intake in the cell
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production of HMG co-enzyme reductase, which will down regulate the LDL receptors to avoid cholesterol overload (toxic)
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What is the problem with the long half-life of LDLs?
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They become oxidized, taken up by macrophages that can't stop taking up cholesterol… they turn inot foam cells… they can burst and then recruitment of more immune cells... and this leads to atherosclerosis
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What is the first step in HDL snthesis?
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ApoA1 is released by the liver… it immediately binds to the ABCA1 receptor, which then form a pre-ß-HDL (a little cholesterol and phospholipids)
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What converts the pre-ß-HDL into an HDL?
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the LCAT enzyme (it is actually an HDL-3 until it takes up cholesterol from cells.)
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What happens after the HDL is loaded with cholesterol?
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goes to the liver
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What is the liver receptor that takes up the HDL? And what is unique about it? What is an important plasma enzyme in this process?
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a) SRB1… b) it allows the the injection of the cholesterol core and recycling of the ApoA1. Thus so every new ApoA1 is a LOT a little bit of old and a little bit of new… c) LCAT
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How does LCAT work in making and HDL function?
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it takes a fatty acid off of a phospholipid and sticks it onto a cholesterol, making it a cholesterol-ester… making more room for more another cholesterol… this increases the HDL cholesterol capacity
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What does cholesterol-ester-tranfer-protein (CETP) do in HDL2 particles?
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It causes a swap of cholesterol for TAGs with ApoB particles… the ApoB takes cholesterol back to the liver and the TAG helps the HDL2 function better. The HDL2 is free to retrieve more cholesterol
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What is the downside of CETP?
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some of the ApoB partilces become LDLs
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Which is the only organ that can break down cholesterol? What enzyme makes cholesterol degradation possible?
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a) the liver… b) cholesterol-7-∂-hydroxylase
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What is the role of micelles?
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a) Micelles transport cholesterol from the liver to the intestines through the biliary trail… b) the help keep cholesterol and TAG in solution in the intestines
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How do micelles get pumped out of the liver cells?
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ATP pump called ABCD11, but overall similar to HDL formation
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How does cholesterol enter the enterocyte? How does regulation of cholesterol take place here?
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a) NPC1L1 channel… b) some of the cholesterol get pumped back out
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Not all cholesterols are created equal. Since the liver goes through so much trouble making bile salts cholesterol, how is this product conserved? What is this process called?
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a) High affinity receptor in the ilium bring all the bile salts back…then back to the liver… b) enterohepatic circulation
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What fraction of cholesterol do we synthesize?
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three times what we eat
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What do the current high cholesterol drugs do?
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They inhibit biosynthesis of cholesterol, lowever LDL cholesterol (by promoting LDL clearance.)
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What do cells make cholesterol from?
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acetate
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What do statins do to inhibit cholesterol synthesis?
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They inhibit HMG-CoA reductase
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How do drugs promote LDL clearance?
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up-regulate LDL receptors on the liver
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By what percentage do statins inhibit cholesterol synthesis? Is this enough?
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40-50%… yes
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What do bile salt sequestrants?
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Prevent reabsorption in the illium… this will cause the use of cholesterol for more bile salts…. The liver then upregulates LDL receptors to replace cholesterol.
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What do cholesterol inhibitors do?
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Inhibit dietary cholesterol absorption… and while the inhibit the biliary reabsorption, they really inhibit the formation of LDLs in the first place
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What do plant sterols to to inhibit cholesterol obsorption?
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competitive uptake inhibitor
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What does Ezetimibe do?
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they block cholesterol entrance into the intestinal cell
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What dodual inhibitors do?
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reduce cholesterol uptake and cholesterol synthesis…
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What does niacin do in lowering cholesterol?
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lowers LDLs by inhibiting VLDL production and raise the HDL level… in the liver it decreases the renal clearance of ApoA1
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What do Fibrates do?
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decrease VLDL formation and balance the HDL (up or down) They also lower TAG…
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Why is this the drug of choice for the obese?
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They also lower TAGs
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