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Flashcards in Lipoprotein Physiology Deck (19)
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Relative polarities of cholesterol ester, triglyceride, unesterified cholesterol and phospholipids

  • un-esterified cholesterol (aka "cholesterol) & phospholipids = more polar
  • triglycerides + cholesterol esters = less polar


Characteristics of lipoproteins (general)

  • named based on density 
  • more triglyceride ==> less dense
  • descriptors: size, associated apo-lipoproteins, and composition (triglyceride vs. cholesterol)
  • 5 classes


Classes of lipoproteins

  • chylomicrons
  • very low density lipoproteins (VLDL)
  • remnant particles & intermediate density lipoproteins (IDL)
  • low density lipoproteins (LDL)
  • high density lipoproteins (HDL)


Characteristics of chylomicrons

  • made by the GI tract from dietary fat
  • physically large and have far more triglyceride than cholesterol (>10:1)
  • This class of particle is responsible for the observed rise in triglyceride levels following a meal.


Characteristics of VLDLs

  • relatively large particles that are triglyceride rich (tg:chol = 5:1) and are made by the liver
  •  source of “basal triglyceride production”
  • They deliver triglyceride to peripheral tissues between meals, but are also made at lower levels in the post-meal period


Characterstics of IDLs

  • metabolic byproducts of the metabolism of chylomicrons and VLDL. 
  • As the triglyceride rich lipoproteins deliver tg to peripheral tissues they become physically smaller and “relatively” cholesterol enriched. 
  • These particles are mid-sized and have roughly equal amounts of triglyceride and cholesterol. 
  • They are atherogenic.



Characteristics of LDLs

  • produced from the metabolism of VLDL. 
  • They have more cholesterol than tg, and are quite atherogenic. 
  • The less tg they contain the smaller and more dense they are. 
  • Small dense LDL are especially atherogenic.
  • They are cleared from the circulation by the liver.



Characteristics of HDLs


  • They collect cholesterol from peripheral tissues and transport it back to the liver. 
  • They also provide a reservoir of phospholipids for other lipoprotein particles, and they can exchange triglyceride and apo-proteins with other particles in the circulation. 
  • HDL cholesterol levels are inversely correlated with atherosclerotic risk presumably through their role in the process of reverse cholesterol transport


Chylomicron pathway

  • lipids then diffuse or are transported across the intestinal wall ==> triglycerides are re-synthesized and packaged into chylomicron particles that contain apoprotein B48.
  • chylomicrons ==> gut lymphatics ==> central circulation where they acquire apoproteins C-2 and E from HDL particles
  • triglyceride in chylomicrons is broken down by lipoprotein lipase (LPL) at the endothelial surface of tissues such as muscle and adipose tissue
  • chylomicron-remnant particles that are taken up by the liver


Chylomicron contents/purpose

  • chylomicrons handles lipids that enter the body through the diet
  • majority of the lipid in the chylomicron is triglyceride


VLDL contents/purpose

  • triglyceride rich lipoprotein synthesized by the liver
  • remainder of its mass made up of phospholipid and protein
  • VLDL particles contain one apoprotein B molecule per particle that remains with it throughout its metabolism = B100
    • B48 = truncated version of B100


VLDL pathway

  •  Following secretion by the liver VLDL acquire apoprotein C-2 and apo-lipoprotein E from HDL in the peripheral circulation
  • VLDL metabolized by LPL ==> VLDL-remnant particles ==> low density lipoproteins (LDL)
  • LDL particles are cleared from the blood by the LDL receptor.
    • most LDL particles are cleared by the liver. 
    • Cholesterol taken up by the LDL receptor at the liver is internalized and regulates hepatic cholesterol synthesis and metabolism


LDL contents/purpose

  • VLDL - most of triglyceride ==> LDL particles contain ~10% triglyceride, and ~45% cholesterol.
  • LDL particles are the major cholesterol carrier in the plasma.
  • LDL particles still contain apo B100.  


HDL contents/purpose

  • high density lipoproteins (HDL) functions in part to bring cholesterol (and to a lesser extent triglyceride) from the periphery back to the liver in what has been called “reverse cholesterol transport”. 
  • Nascent HDL containing the main structural apo-protein apo A1
    • synthesized by the liver and intestine
    • circulates in plasma and picks up free cholesterol from peripheral tissues via diffusion and facilitated transport via the ABC-A1 cassette.


Mechanism of HDL pathway

  • Nascent HDL circulates at periphery
  • traps free cholesterol by converting to less polar cholesterol ester w/lecithin cholesterol acyltransferase (LCAT)
  • HDL matures ==> HDL3 transfers cholesterol esters to VLDL in exchange for triglycerides w/cholesterol exter transfer protein (CETP)
  • HDL3 ==> HDL2 ==> liver


Fxn of ABC A1

  • ATP binding cassette (ABC) transporters appear to be very important in the transport of cholesterol from peripheral tissues to apo A-1, the core apoprotein of HDL
  • no ABC A1 ==> very low levels of HDL cholesterol ==> premature atherosclerosis


Fxn of LCAT

  • catalyses the transfer of a fatty acids from the phospholipid lecithin to un-esterified cholesterol. 
  • ==> cholesterol ester which is very non-polar and which is then more tightly bound to the HDL particle ==> more effectively transported back to the liver
  • Lack of LCAT ==> low HDL ==> renal failure, corneal opacities


Fxn of CETP

  • Cholesterol ester transfer protein (CETP) is a protein that catalyzes the exchange of the non-polar lipids
    • cholesterol esters (CE) and triglycerides (tg) between lipoprotein particles of different classe
  • CE from HDL is exchanged for tg present in VLDL and remnants.
  • alternative route of clearance for triglyceride


Major fxns of apolipoproteins + examples

  • structural background of lipoprotein particle
    • apoB48 (chylomicrons)
    • apoB100 (VLDL & LDL)
    • apo A1 (HDL)
  • enzymatic cofactors
    • apoC2  = cofactor for LPL
  • ligands for receptors
    • apoB100 = ligand for LDL receptor
    • apo E = ligand for remnant receptor
  • unknown; assoc. w/atherosclerosis
    • apo(a)