Term
| Describe the composition and respective physiological roles of the basic lipoprotein classes |
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Definition
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Term
| Describe the origin (genesis) and catabolism of each major lipoprotein class and their respective roles as CHD risk indicators |
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Definition
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Term
| Describe the regulation of cholesterol biosynthesis via HMG-CoA reductase. |
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Definition
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Term
| Describe the low density lipoprotein pathway and its relevance to atherosclerosis and the risk of coronary heart disease in detail |
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Definition
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Term
| Describe the mechanism of action of bile acid sequestrants and statin drugs |
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Definition
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Term
| How oxidized LDL contributes to thrombogenesis |
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Definition
| Oxidized LDL activates macrophages, stimulates TF expression, which leads to hypercoagulability (accelerated thrombosis) |
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Term
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Definition
Key risk factor for atherosclerosis
Abnormal pattern developing in the amount or distribution of blood lipids (TG and cholesterol) and their impact on atherosclerosis |
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Term
Chylomicrons
- major core lipid
- metabolic function
- synthesis/metabolism |
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Definition
Triglycerides
transport of dietary triglycerides to adipose tissue and muscle tissue
Nascent TAG-rich chylomicrons (CM) are produced in intestinal mucosal cells, primarily from dietary lipids.
When CM reaches plasma, it is modified by receiving apolipoproteins from circulating HDL. Apo C-II activates lipoprotein lipase, which hydrolyzes TAG in the CM to glycerol and FA. (Lipoprotein lipase synthesis & transfer is stimulated by insulin/fed state.)
*Patients with a deficiency in lipoprotein lipase or apoC-II show a dramatic accumulation of chylomicrons in the plasma (hypertriacylglycerolemia), even in the fasted state*
Cholesteryl ester-rich CM remnants bind to liver where they're endocytosed.
[image]
[image]
[image] |
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Term
VLDL
- major core lipid
- metabolic function
- synthesis/metabolism |
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Definition
Triglycerides
transport of endogenously synthesized (hepatic) triglycerides to adipose tissue and muscle tissue
Liver secretes nascent TAG-rich VLDL containing apo B100.
In plasma, VLDL receives apoproteins from HDL, apo C-II activates lipoprotein lipase which degrades TAG in VLDL in tissues (e.g. adipose).
*Cholesteryl ester transfer protein (CETP) facilitates the transfer of TAG from VLDL to HDL in exchange for cholesteryl esters from HDL to VLDL.
VLDL --TAG--> HDL
VLDL <--CE-- HDL
VLDL is converted in plasma to LDL
[image] |
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Term
LDL
- major core lipid
- metabolic function
- synthesis/metabolism |
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Definition
Cholesteryl esters (CE)
transport of cholesterol to peripheral cells and to liver cells - atherogenic
LDL binds to B100 receptors on tissues, where they are endocytosed. Apo B-100 is located on the surface of LDL
*LDL receptor deficiency -> high cholesterol (familial hypercholesterolemia/type II hyperlipidemia)*
Lysosome is degraded, AA/FA/cholesterol is used by cell.
Oversupply of cholesterol inhibits HMG CoA reductase (de novo cholesterol synth d/c) and synthesis of new LDL receptor protein. |
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Term
HDL
- major core lipid
- metabolic function
- synthesis/metabolism |
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Definition
Cholesteryl esters (CE)
transport of cholesterol from peripheral tissues to the liver - anti-atherogenic
Formed in blood by addition of lipid to apo A-1; picks up cholesterol from other lipoproteins or tissues, then LCAT forms CE in HDL to create mature serum HDL.
Functions of HDL:
- reservoir of apolipoproteins (inc. apo C-II, -> VLDL and chylomicrons, activate lipoprotein lipase)
- uptake of unesterified cholesterol
- esterification of cholesterol (by PCAT; CTEP moves some of the cholesteryl esters from HDL to VLDL in exchange for TAG)
- *reverse cholesterol transport* (peripheral cells -> HDL -> liver for bile acid synthesis or disposal via bile) |
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Term
Apolipoproteins & function
*B-100, C-II* |
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Definition
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Term
| Mechanism of triglyceride transport and metabolism: sequence of events |
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Definition
1. secretion of chylomicrons (Small intestine)
2. role of lipoprotein lipase, hepatic lipase (capillary endothelium)
3. generation (blood) and receptor uptake of remnant particles (liver)
4. biosynthesis of VLDL ( Liver)
5. metabolism of VLDL: receptor uptake (liver) and metabolism of IDL (blood)
6. generation of LDL (blood) |
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Term
Cholesterol biosynthesis
(pathway, image) |
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Definition
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Term
| Bile acid sequestrants, statins |
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Definition
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Term
| Effect of CETP inhibition on plasma cholesterol transport |
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Definition
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