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

Triacylglycerol % of dry wt Lipoprotein class Density (g/mL) Diameter (nm) Protein % of dry wt Phospholipid % Triacylglycerol % of dry wt HDL 1.063-1.21 5 – 15 33 29 8 LDL 1.019 – 1.063 18 – 28 25 21 4 IDL 1.006-1.019 25 - 50 18 22 31 VLDL 0.95 – 1.006 30 - 80 10 50 chylomicrons < 0.95 100 - 500 1 - 2 7 84

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).

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

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

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

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

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

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