Physiology of Lipoprotein Metabolism

a key to effective treatment of cardiovascular disease is understanding the body's complex lipoprotein transport system at the operational helm are Apple lipoproteins which through their various functions such as enzyme activation and receptor binding choreograph the transport of lipids from sites of absorption or synthesis to sites of utilization this system cycles triglycerides for distribution to muscle for energy use or to adipose tissue for storage and it's cycles cholesterol for distribution throughout the body for cell membrane bile acid and steroid hormone synthesis a complementary cycle called reverse cholesterol transport completes the system Applebee containing lipoproteins also called non HDL comprised the lipid delivery pathway while a po a one containing lipoproteins or HDL participate in reverse cholesterol transport Applebee containing lipoproteins originate from two sources an intestinal Applebee 48 lineage and a hepatic Applebee 100 lineage traveling along similar pathways Applebee particles are remodeled into smaller and smaller cholesterol rich remnants as triglycerides are released in the form of fatty acids to peripheral tissue let's take a closer look at this process the newly assembled Applebee containing lipoproteins are secreted from the intestine or liver into the lymph or plasma respectively secreted with them are apolipoproteins ii c2 and c3 these apolipoproteins may also be acquired from HDL with attachment of proteoglycans on capillary endothelium the lipoprotein remodeling process begins here apple c2 activates lipoprotein lipase PL which hydrolyzes the lipoproteins core triglycerides into free fatty acids which diffused through the capillary to muscle or adipose cells as fatty acids exit the lipoproteins become smaller and smaller remnants in remodeling of the Appleby 100 lineage a further step by hepatic lipase HL transforms remnant IDL particles to LDL during the modeling remnants of both Appleby 48 and Appleby 100 pathways shed apolipoproteins II c2 and c3 which then reassociate with HDL eventually most Appleby remnants are recycled to the liver through the LDL receptor related protein l RP or LDL receptors however Apple be remnants can have other metabolic fates for example LDL may be taken up by peripheral cells for its cholesterol content or of more clinical concern chylomicron remnants and LDL may become targets for uptake by the arterial wall macrophage excess Applebee containing particles can invade the arterial wall become oxidized and be taken up by macrophage scavenger receptors creating the foam cells that lead to atheroma now let's examine the complementary a po a 1 or HDL pathway that protects from a thorough Genesis hdls to major a thorough protective roles are reversed cholesterol transport and properties which prevent LDL oxidation a key trigger for a thorough Genesis let's look at reverse cholesterol transport to begin horley lipid ated Apple a1 is secreted from the liver and intestine and released into the plasma for circulation to peripheral cells where it removes excess cholesterol forming nascent HDL HDL removal of cholesterol from cells is of utmost importance when those cells are cholesterol Laden arterial wall macrophages let's examine several of HDL cholesterol removing mechanisms excess cholesterol in the macrophage triggers up regulation of the abca1 transporter and a hydrolase which converts cholesterol ester in the lipid pool to free cholesterol the abca1 transporter operates to harvest this free cholesterol and deliver it to the cell membrane where it is acquired by poorly lipid ated appo a 1 to create nascent HDL the transporter shuttles back and forth transferring cholesterol from the macrophage to HDL next the free cholesterol on HDL surface is esterified by lecithin cholesterol acyl transferase or l capped the cholesterol ester then moves to the lipoproteins core forming the more spherical mature HDL three further cholesterol removal by HDL three occurs through SRB one receptors in membrane cholesterol pools as HDL three collects more cholesterol and is acted on by l cat it expands to HDL two as we've seen abca1 and SRB one are key devices for cholesterol a flux however HDL also collects cholesterol from both lipid rafts and caviola within the cell membrane in these ways HDL facilitates cholesterol efflux from the macrophage now rich in cholesterol esters HDL to engages in an exchange with triglyceride rich lipoproteins mediated by cholesterol ester transfer protein CET P cholesterol ester from HDL to is transferred to Apple B containing lipoproteins in a one to one exchange for triglycerides the result further cholesterol enrichment of Apple B lipoproteins and triglyceride enrichment of HDL HDL may now have one of three fates HDLs triglycerides may be hydrolyzed by hepatic lipase converting it back to HDL 3 or HDL 2 can return to the liver interacting with scavenger receptor SR b1 which removes cholesterol converting it back to HDL 3 or finally HDL 2 may be catabolized by the liver as we have seen these complementary systems work in elegant harmony to choreograph the body's lipid needs and as science continues to unravel these intricacies of normal lipid metabolism our ability to understand diagnose and manage various dis lip además continues to improve ah

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Keywords: Lipoprotein, Atherogenesis, Physiology, Lipid Metabolism

Id: 97uiV4RiSAY

Length: 7min 57sec (477 seconds)

Published: Mon Aug 17 2009