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45 Cards in this Set
- Front
- Back
What are the most abundant lipids and their functions in the human body?
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-Triglycerides: Major energy source for cells
-Phospholipids: Major component of cell membranes -Cholesterol: Cell growth, cell division, membrane repair, steroid hormone production, bile salts, MAJORITY MADE IN THE LIVER |
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Where is the majority of cholesterol made?
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In the liver
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What are triglycerides?
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3 fatty acids connected to glycerol via ester linkage
High density energy store |
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What are phospholipids?
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2 fatty acids attached to a glycerol with a phosphate and polar head group
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What are the sources, biosynthesis and degradation of cholesterol and cholesterol esters?
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Diet: Only found in animal fat
Biosynthesis: Primarily in the liver from acetyl-CoA; (inhibited by LDL uptake) Degradation: Only occurs in the liver |
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What is the precentage of fatty acids presents in FREE FORM and what are they derived from?
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- Only 2-5% of fatty acid is present in FREE FORM (unesterified) - 95% are in the form of fatty acid esters
-Derived from: *Intracellular hydrolysis of triglycerides in hepatic or adipose cells *Lipoprotein lipase acting on circulating lipoproteins |
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How are FFA stored and mobilized during feed state and fasting?
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-During feed state
*Insulin - inhibits hormone sensitive lipase and stimulates triglycerides synthesis, stimulates LPL *Results in storage of triglycerides -During Fasting: *Drop in insulin activates HSL *Triglycerides hydrolyzed in adipocytes |
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What are lipoproteins?
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Lipids
Apolipoproteins Lipids are insoluble Lipoproteins transport lipids Spherical soluble particle |
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What are apoproteins?
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Proteins associated with lipoproteins
Functions: -Structural -Binding sites for receptors -Activators or co-enzymes for lipid metabolism *Direct the fate of lipoproteins |
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How are lipoproteins classified?
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Based on buoyant density compared to physiological saline:
*Chylomicron and Chylomicron remnants *VLDL - Very Low Density Lipoprotein *IDL - Intermediate Density Lipoprotein *LDL - Low Density Lipoprotein *HDL - High Density Lipoprotein (GOOD) |
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What are the characteristics of the larger lipoprotein particles?
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(Chylomicrons and VLDL)
-High content of triglycerides -Lower density |
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What are the characteristics of the smaller lipoprotein particles?
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(LDL and HDL)
-Less triglycerides -Greater relative mass of protein -Enriched in cholesterol esters -Greater density |
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What are characteristics common among all lipoproteins?
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-Protein content varies (number and kinds)
-Proteins can exchange -Surface phospholipids and cholesterol can transfer -Cholesterol esters and trigycerides need CETP (cholesterol ester transfer protein) |
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What are the exception in lipoproteins?
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apoB 100 and B48 (structural)
Do not co-exist on the same particle Only one apoB 100 or B48 molecule Cannot exchange |
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What are the source, function and apoproteins in chylomicrons?
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Source: Gut
Function: Transport of dietary TG *FFA --> Adipose/muscle *CE --> Liver via remnants Apoproteins: B48, CII, E |
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What is the source, function and apoproteins in VLDL?
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Source: Gut
Function: Transport of endogenously synthesized TG *FFA --> Adipose/muscle *CE --> LDL Apoproteins: B100, CII, E |
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What is the source, function and apoproteins in LDL?
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Source: Blood
Function: Delivers cholesterol to peripheral tissues *CE to liver *Peripheral Cells Apoporoteins: B100 |
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What is the source, function and apoproteins in HDL?
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Source: Liver
Function: REVERSE CHOLESTEROL TRANSPORT *Removes "used cholesterol from tissues *Donates apolipoproteins to CM and VLDL Apoproteins: A1, CII, E |
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What is the site of action and function of Apo A1?
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Site of Action: Blood, plasma membrane
Function: Activates LCAT and CETP; binds to apo A1 receptors on cells requiring cholesterol extraction |
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What is the site of action and function of Apo B48?
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Site of action: Gut
Function: Export of chylomicrons from intestinal cells |
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What is the site of action and function of Apo B100?
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Site of Action: Various cells
Function: Ligand for LDL receptor; export of liver VLDL |
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What is the site of action and function of Apo CII?
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Site of Action: Capillary walls
Function: Activates lipoprotein lipase |
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What is the site of action and function of Apo E?
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Site of action: Liver
Function: Receptor ligand - clears remnants, IDL, and HDL |
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What are the similarities and differences between apoB100 and apoB48?
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-Same gene
-ApoB48; 49% of apoB100 in size -ApoB48 is produced exclusively by the intestine: *result of tissue-specific expression of an mRNA-editing enzyme activity (editase) *a substitution of thymidine (T) for cytidine (C) creates a premature stop codon |
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What are chylomicrons?
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-largest of the lipoproteins
-Most triglyceride-rich -Least dense -Relatively short-lived -Nearly absent in the fasting state |
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What are the characteristics of chylomicrons?
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-Assembled in intestinal mucosal cells
-Enter the lymphatic system then blood via the thoracic duct -Contain apoprotein B48; acquire other apoproteins from high density lipoproteins (HDL). -TRANSPORT DIETARY TG: *to the adipose tissue (storage) *to muscles (for energy) |
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How are chylomicrons assembled?
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-Size of particle depends on the amount of triglyceride available
-Enter secretory vesicles -Picks up apo A, C and E in plasma -TG composition closely resembles dietary intake |
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What do Very Low Density Lipoproteins (VLDL) contain and transport?
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Contain:
-Nascent VLDL contain apo B100 -Contain mostly TG but with a significant amount of cholesterol and cholesterol ester Transport: -Endogenously synthesized TG to the extra hepatic tissues (storage or energy) |
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What are the characteristics of VLDLs?
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-Large lipoproteins
-Triglyceride-rich particles -Produced by the liver -Acted upon by LPL to liberate FFA -Lipolysis creates smaller, more cholesterol ester-rich VLDL remnants -apoB100 as the major structural apoprotein |
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How are VLDLs assembled?
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-Occurs in the liver:
*hepatocytes, uptake plasma lipoproteins *hepatocytes secrete VLDL -Three sources of the fatty acids *plasma FFA that dissociate from albumin *from triglyceride-rich lipoproteins that have undergone receptor-mediated endocytosis *synthesized in the liver de novo -ER/Golgi same as for chylomicrons -particles enter secretory vesicles for release in the space of Disse |
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What are Intermediate-density lipoproteins (IDLs)?
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-50% of small VLDL are lipolytically converted to IDL
-Contain apoB100 -Enriched in cholesterol esters |
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What are the characteristics of low-density lipoproteins (LDLs)?
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-Cholesterol-rich
-95% of protein is apoB100 -70% of the cholesterol in plasma -From lipolysis of VLDL -Deliver cholesterol to extra hepatic tissue*** -High level of plasma LDL or apoB100 is the best single predictor of increased risk for atherosclerosis |
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How are IDLs and LDLs formed?
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-50% of small VLDL are converted to IDL and LDL
-Are VLDL remnants!!!!***** -Delipidation: *Become depleted in triglycerides *Become enriched in cholesterol esters |
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What are the 3 pathways of lipoprotein metabolism?
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1. Exogenous/chylomicron pathway (dietary fat)
2. Endogenous pathway (lipids synthesized by the liver) 3. HDL metabolism (apoproteins transfer, cholesteryl ester transfer, REVERSE CHOLESTEROL TRANSPORT) |
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What is the site of action, activator and function of Lipoprotein lipase (LPL)?
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Site of action: capillary walls
Activator: apo CII Function: excises FFA from TAGs in chylomicrons and VLDLs for adipose and muscle |
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What are the functions of HDLs?
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-HDL carries "used" cholesterol back to the liver
-Donates some CE to circulating VLDL for redistribution to tissues -HDL taken up by liver and degraded -Cholesterol is excreted as bile salts or repackaged in VLDL -Cholesterol synthesis in the liver is regulated by the cholesterol arriving through HDL (and dietary cholesterol returned by chylomicron remnants). |
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How do statins influence HDL and LDL levels?
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HDL: raised
LDL: Lowered |
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How are lipoproteins cleared?
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-irreversible removal from plasma
-relatively rapid -Plasma half life: *Large VLDL - minutes *Small VLDL and IDL - 1-2 hours *LDL - 2-3 days (loss of apoE; loss of affinity for LDL receptors); allows to gain access to tissues -Enrichment of apoE is important - increases affinity for lipoprotein receptors |
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How is LDL cleared?
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-40% of plasma LDL is cleared by the liver
-60% of plasma LDL is cleared by extrahepatic tissues -LDL cholesterol is preferentially used (as opposed to de novo cholesterol syn.) -70% of LDL clearance is mediated by LDL receptorsl remainder by scavenger receptors |
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What is the LDL Receptor Pathway?
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-Found in clathrin coated pits (endocytosis)
-Receptor is recycled -The LDL is degraded releasing lipid cargo -Cholesterol uptake down regulates the cells own production of cholesterol and down regulates LDL receptor synthesis -Mutations in LDL receptors causes increased plasma LDL levels (ie increased cholesterol levels) accelerates progress of athersclerosis (Familial hyperlipedimias) |
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What is corneal arcus?
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Associated with hyperlipoproteinemia types 2 and 3. In males <40 yrs, predictive of increased risk of coronary artery disease
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Where is tendon xanthoma found?
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Found in type 2a hyperlipoproteinemia
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What are the mechanisms of Atherogenesis?
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-accumulation of lipoprotein due to shif of equilibrium
-Common cause of accelerated atherosclerosis is a deficiency of LDL receptors -Inherited defect or high cholesterol, high saturated fat diet |
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What occurs as a result of the formation of oxidized LDL?
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1. Uptake of oxidized LDL by "scaventer receptors" on macrophages that invade artery walls
2. Elicits CE deposition in artery walls 3. Atherosclerosis/CAD can develop |
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How is arterial plaque formed?
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-Oxidized LDL stimulates endothelial cells, releasing chemokins and cytokines
*recruits monocytes into the arterial wall -macrophages become enlarged and full of lipid: foam cells -Foam cells form the "fatty streak", part of the atherogenic plaque -Elevated LDL *Increased residence time in plasma *Increased modification/oxidation of LDL |