Harpers

LIPID TRANSPORT & STORAGE / 207FreecholesterolIntegralapoprotein(eg, apo B)Peripheral apoprotein(eg, apo C)PhospholipidCholesterylesterTriacylglycerolCore of mainlynonpolar lipidsMonolayer of mainlyamphipathic lipidsFigure 25–1. Generalized structure of a plasmalipoprotein. The similarities with the structure of theplasma membrane are to be noted. Small amounts ofcholesteryl ester and triacylglycerol are to be found inthe surface layer and a little free cholesterol in the core.Free fatty acids are removed from the blood extremelyrapidly and oxidized (fulfilling 25–50% of energyrequirements in starvation) or esterified to formtriacylglycerol in the tissues. In starvation, esterifiedlipids from the circulation or in the tissues are oxidizedas well, particularly in heart and skeletal muscle cells,where considerable stores of lipid are to be found.The free fatty acid uptake by tissues is related directlyto the plasma free fatty acid concentration, whichin turn is determined by the rate of lipolysis in adiposetissue. After dissociation of the fatty acid-albumin complexat the plasma membrane, fatty acids bind to amembrane fatty acid transport protein that acts as atransmembrane cotransporter with Na + . On enteringthe cytosol, free fatty acids are bound by intracellularfatty acid-binding proteins. The role of these proteinsin intracellular transport is thought to be similar to thatof serum albumin in extracellular transport of longchainfatty acids.TRIACYLGLYCEROL IS TRANSPORTEDFROM THE INTESTINES INCHYLOMICRONS & FROM THE LIVER INVERY LOW DENSITY LIPOPROTEINSBy definition, chylomicrons are found in chyle formedonly by the lymphatic system draining the intestine.They are responsible for the transport of all dietarylipids into the circulation. Small quantities of VLDLare also to be found in chyle; however, most of theplasma VLDL are of hepatic origin. They are the vehiclesof transport of triacylglycerol from the liver tothe extrahepatic tissues.There are striking similarities in the mechanisms offormation of chylomicrons by intestinal cells and ofVLDL by hepatic parenchymal cells (Figure 25–2), perhapsbecause—apart from the mammary gland—theintestine and liver are the only tissues from which particulatelipid is secreted. Newly secreted or “nascent”chylomicrons and VLDL contain only a small amountof apolipoproteins C and E, and the full complement isacquired from HDL in the circulation (Figures 25–3and 25–4). Apo B is essential for chylomicron andVLDL formation. In abetalipoproteinemia (a rare disease),lipoproteins containing apo B are not formed andlipid droplets accumulate in the intestine and liver.A more detailed account of the factors controllinghepatic VLDL secretion is given below.CHYLOMICRONS & VERY LOWDENSITY LIPOPROTEINS ARERAPIDLY CATABOLIZEDThe clearance of labeled chylomicrons from the bloodis rapid, the half-time of disappearance being under 1hour in humans. Larger particles are catabolized morequickly than smaller ones. Fatty acids originating fromchylomicron triacylglycerol are delivered mainly to adiposetissue, heart, and muscle (80%), while about 20%goes to the liver. However, the liver does not metabolizenative chylomicrons or VLDL significantly; thus,the fatty acids in the liver must be secondary to theirmetabolism in extrahepatic tissues.Triacylglycerols of Chylomicrons & VLDLAre Hydrolyzed by Lipoprotein LipaseLipoprotein lipase is located on the walls of blood capillaries,anchored to the endothelium by negativelycharged proteoglycan chains of heparan sulfate. It hasbeen found in heart, adipose tissue, spleen, lung, renalmedulla, aorta, diaphragm, and lactating mammarygland, though it is not active in adult liver. It is notnormally found in blood; however, following injectionof heparin, lipoprotein lipase is released from its heparansulfate binding into the circulation. Hepatic lipaseis bound to the sinusoidal surface of liver cells andis released by heparin. This enzyme, however, does notreact readily with chylomicrons or VLDL but is concernedwith chylomicron remnant and HDL metabolism.Both phospholipids and apo C-II are required ascofactors for lipoprotein lipase activity, while apo A-II