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Lipoproteins Function: Transport of fat soluble substances Types:1) Chylomicron 2) VLDL 3) LDL 4) HDL.

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Presentation on theme: "Lipoproteins Function: Transport of fat soluble substances Types:1) Chylomicron 2) VLDL 3) LDL 4) HDL."— Presentation transcript:

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2 Lipoproteins Function: Transport of fat soluble substances Types:1) Chylomicron 2) VLDL 3) LDL 4) HDL

3 Lipoprotein class Density (g/mL) Diameter (nm) Protein % of dry wt Phospho lipid % Triacylglycerol % of dry wt HDL1.063-1.215 – 1533298 LDL1.019 – 1.063 18 – 2825214 IDL1.006-1.01925 - 50182231 VLDL0.95 – 1.006 30 - 80101850 chylomicrons< 0.95100 - 5001 - 2784

4 Apolipoproteins: specific lipid-binding proteins that attach to the surface intracellular recognition for exocytosis of the nascent particle after synthesis activation 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: chylomicrons very low density lipoproteins (VLDL) low density lipoproteins (LDL) high density lipoproteins (HDL) Subfraction: intermediate density lipoproteins (IDL) Electrophoretic mobility (charge): HDLs =  lipoproteins LDLs =  -lipoproteins VLDLs = pre-  lipoproteins (intermediate between  and  mobility).

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11 LIVER ApoB48 aids with chylo- micron assembly Lymph system: Chylomicrons to capillaries via lymph INTESTINEINTESTINE non-hepatic tissues C E Figure 3. Exogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and the remnants take cholesterol to the liver Nascent chylo- microns acquire apo CII (C) and E (E) from HDL chylomicron interacts with lipoprotein lipase removing FFA

12 Chylomicron (or VLDL) Apo CII LIPOPROTEIN LIPASE Polysaccharide Chain Endothelial Surface of cell Triacylglycerol in core Free fatty acids Glycerol To Liver Free fatty acids In cellulo (muscle & adipose) Capillary Figure 4. Lipoprotein lipase action on chylomicron triacylglycerol (an identical reaction occurs with VLDL)

13 LIVER ApoB48 chylomicron remnants lose CII to HDL non-hepatic tissues C E E E EE CC C EEE Liver: apo E receptor takes up remnants to deliver cholesterol Figure 3. Exogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and the remnants take cholesterol to the liver Lymph system: INTESTINEINTESTINE C E chylomicron acquires apo CII (C) and E (E) from HDL chylomicron interacts with lipoprotein lipase removing FFA

14 B100 (B) helps assemble and export nascent VLDL LIVER nascent VLDL acquires apo CII (C) and apo E (E) from HDL C E B B B B B BBB bile acids HDL scavenge cholesterol C E BBB Figure 5. The liver-directed endogenous pathway of lipoprotein metabolism. non-hepatic tissues LPL hydrolyze TAGs; FFA uptake; LDL circulate to tissues apo B100 on LDL bind to receptor LDL taken into the cell to deliver cholesterol CII and E release to HDL Apo E binds liver receptor Cholesterol uptake; excreted as bile acids

15 Nascent Chylomicron Assembly in Gut Mediated by B48 Nascent HDL Assembled in liver Loans apo E/ apo CII to nascent chylomicrons Mature Chylomicron Apo E and CII added from HDL Lipoprotein Lipase capillary walls hydrolyzes TAG deliver FFA into adipose/muscle Mature HDL CE from peripheral cells via LCAT activated by apo A1 Apo CII returned by chylomicrons Chylomicron Remnant from mature chylomicron apo CII returned to HDL Chylomicrons: Exogenous Pathway HDL: Both Pathways apo CII Triacylglycerol Cholesterol ester Phospholipid E CII A1 E B48 CII A1 E CII B48 apo E & CII from HDL B48 adipose & muscle FFA CII EEEE Fig. 6 Chylomicron Processing and Interface with HDL Mature Chylomicron Apo E and CII added from HDL CII activates LPL B48

16 free pool of cholesterol LDL CE endocytosis late endosome ACEH CE  cholesterol B100  amino acids NPC-1 mediated transfer Cholesterol Esterase Cholesterol metabolism to bile acids or steroids Golgi Cholesterol release for transport to liver Membrane Cholesterol ACAT (stimulated by cholesterol) CE CE stored in droplets CERP LCATLCAT Apo A1 receptor A1 CII E A1 E CII CE in nascent HDL Apo A1 binds to receptor, activates CERP to pump out cholesterol, and LCAT to esterify cholesterol Mature HDL: Cleared by liver oooooo clathrin- coated pit LDL receptor oooooo vesicle Recycling of receptor transport vesicle- lysosome fuse forming late endosome sorting endosome: ligand/receptor dissociation lysosome Figure 7. Cellular cholesterol uptake, metabolism and release. Reverse Cholesterol Transport Recycling of receptor and clathrin


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