2Lipoproteins Function: Transport of fat soluble substances Types: 1) Chylomicron2) VLDL3) LDL4) HDL
3Triacylglycerol % of dry wt Lipoprotein classDensity (g/mL)Diameter (nm)Protein % of dry wtPhospholipid %Triacylglycerol % of dry wtHDL5 – 1533298LDL1.019 – 1.06318 – 2825214IDL182231VLDL0.95 – 1.0061050chylomicrons< 0.951 - 2784
4Apolipoproteins: specific lipid-binding proteins that attach to the surface intracellular recognition for exocytosis of the nascent particle after synthesisactivation of lipid-processing enzymes in the bloodstream,binding to cell surface receptors for endocytosis and clearance.Main lipid components: triacylglycerols, cholesterol esters, phospholipids.Major lipoproteins:chylomicronsvery low density lipoproteins (VLDL)low density lipoproteins (LDL)high density lipoproteins (HDL)Subfraction: intermediate density lipoproteins (IDL)Electrophoretic mobility (charge):HDLs = lipoproteinsLDLs = -lipoproteinsVLDLs = pre- lipoproteins (intermediate between and mobility).
11chylomicron interacts with lipoprotein lipase removing FFA Lymph system:Chylomicrons to capillaries via lymphINTESTINENascent chylo-microns acquire apo CII (C) and E (E) from HDLnon-hepatic tissuesC EC EC EC EApoB48 aids with chylo-micron assemblyLIVERFigure 3. Exogenous pathway of lipid transport.Chylomicrons carry dietary fatty acids to tissuesand the remnants take cholesterol to the liver
12Triacylglycerolin coreChylomicron (or VLDL)To LiverApo CIILIPOPROTEIN LIPASEGlycerolFree fatty acidsPolysaccharideChainEndothelialSurface of cellCapillaryIn cellulo (muscle & adipose)Free fatty acidsFigure 4. Lipoprotein lipase action on chylomicron triacylglycerol (an identical reaction occurs with VLDL)
13chylomicron interacts with lipoprotein lipase removing FFA Lymph system:INTESTINEC Echylomicron acquires apo CII (C) and E (E) from HDLnon-hepatic tissuesC EC ECEchylomicron remnants lose CII to HDLCEApoB48ELiver: apo E receptor takes up remnants to deliver cholesterolLIVERFigure 3. Exogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and the remnants take cholesterol to the liver
14nascent VLDL acquires apo CII (C) and apo E (E) from HDL LPL hydrolyze TAGs; FFA uptake; LDL circulate to tissuesB100 (B) helps assemble and export nascent VLDLnon-hepatic tissuesLIVERC EC EBC EC EC Ebile acidsBCII and E release to HDLCholesterol uptake; excreted as bile acidsapo B100 on LDL bind to receptorBBLDL taken into the cell to deliver cholesterolApo E binds liver receptorHDL scavenge cholesterolFigure 5. The liver-directed endogenous pathway of lipoprotein metabolism.
15Fig. 6 Chylomicron Processing and Interface with HDL Chylomicrons:Exogenous PathwayFig. 6 Chylomicron Processing and Interface with HDLHDL: Both PathwaysNascent ChylomicronAssembly in GutMediated by B48B48Nascent HDLAssembled in liverLoans apo E/ apo CII to nascent chylomicronsECIIA1apo E & CIIfrom HDLEEB48ECIIECIIMature ChylomicronApo E and CII added from HDLCII activates LPLMature ChylomicronApo E and CII added from HDLLipoprotein Lipasecapillary wallshydrolyzes TAGdeliver FFA into adipose/muscleB48ECIICIICIIadipose &muscleFFAMature HDLCE from peripheral cells via LCAT activated by apo A1Apo CII returned by chylomicronsapo CIIA1Chylomicron Remnantfrom mature chylomicronapo CII returned to HDLCIICIICIIEB48TriacylglycerolCholesterol esterPhospholipid
16Figure 7. Cellular cholesterol uptake, metabolism and release. sorting endosome: ligand/receptor dissociationLDL receptortransport vesicle- lysosome fuse forming late endosomeRecycling of receptor and clathrinRecycling of receptorlysosomeoooclathrin-coated pitGolgilate endosomeNPC-1 mediated transferooofree pool ofcholesterolACEHCE cholesterolB100 amino acidsACAT (stimulated by cholesterol)Cholesterol release for transport to liverendocytosisCholesterol EsteraseCE stored in dropletsvesicleCECELDLCECERPCholesterol metabolism to bile acids or steroidsMembraneCholesterolApo A1 receptorLCATA1ECIICE in nascent HDLApo A1 binds to receptor, activates CERP to pump out cholesterol, and LCAT to esterify cholesterolA1CIIEReverseCholesterolTransportFigure 7. Cellular cholesterol uptake, metabolism and release.Mature HDL:Cleared by liver