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HANDBOOK OF PHYSIOLOOY 



CIRCULATION II 



haps to other substances, and consist principally of 

 fatty acids common in the diet, such as palmitate, 

 stearate, oleate, and linoleate. 



Chylomicrons 



The elaboration of chylomicrons by the intestinal 

 mucosa has been discussed. These small particles 

 enter the systemic circulation via the intestinal lac- 

 teals and thoracic duct. The chylomicrons in the 

 blood are responsible for the visible lipemia that 

 occurs after a meal containing an appreciable quan- 

 tity of fat. Similar (but not identical) particles manu- 

 factured by the liver seem to be responsible for the 

 lactescence that occurs in uncontrolled diabetes, 

 nephrosis, and carbohydrate-induced hyperlipemia. 

 From an analytical standpoint, chylomicrons have 

 been characterized as the material floating at the top 

 of a tube when chyle or serum is layered under sa- 

 line of density 1 006 and centrifuged for a few min- 

 utes at high speed. Varying speeds and time of cen- 

 trifugation have been suggested, but it is assumed 

 that the lower the speed and the shorter the time 

 of centrifugation, the purer will be the chylomicron 

 fraction (71). One procedure (135) uses 9500 g for 

 10 min. The actual density of chylomicrons is 0.94 g 

 per ml. 



When chylomicrons are released into the systemic 

 circulation from the thoracic duct, they are removed 

 with considerable rapidity by the liver and extra- 

 hepatic tissues. The mechanisms of removal are in- 

 completely understood; however, these small fat 

 particles apparently are not hydrolyzed to any appre- 

 ciable degree in the circulating blood, although evi- 

 dence for intravascular hydrolysis has been pre- 

 sented (62). To some extent, fatty acids may be split 

 away from chylomicron triglyceride through the 

 intervention of the enzyme, lipoprotein lipase, but 

 this action probably occurs primarily at endothelial 

 surfaces and other cell membranes and not in the 

 main stream of the circulation (71). 



More important mechanisms for chylomicron 

 removal may include direct diffusion into cells through 

 "pores," and phagocytosis by appropriate cells. 

 When the subject is in the postabsorptive state and 

 carbohydrate no longer is readily available, a larger 

 proportion of the chylomicrons from a test meal of 

 fat will be removed by liver and muscle; when excess 

 carbohydrate is available (that is, during hyper- 

 glycemia), the chylomicrons are shunted to a greater 

 extent to the fat depots. The clearing of visible 

 lipemia after ingestion of fat may be inhibited if a 



previous fat load has been given and has recently 

 been cleared. Although a large amount of chylo- 

 micron fatty acid is directly oxidized, some of it may 

 recirculate in the form of free fatty acid. Thus, a 

 variable rise in free fatty acids occurs in blood during 

 the course of an alimentary lipemia (71, 72). 



The Lipoproteins 



In normal human plasma, the lipoproteins consti- 

 tute approximately 12 to 15 per cent of the total 

 protein (155). A fundamental difference between the 

 lipoproteins and the remainder of the plasma pro- 

 teins is that the former are lipid-laden molecules with 

 relatively low density. The plasma lipoproteins ex- 

 hibit densities from 0.9 to 1.2, in contrast to densities 

 of 1.26 to 1.38 for most other proteins. Thus, the 

 ultracentrifuge has become a useful tool in the sepa- 

 ration of the plasma proteins and lipoproteins, utiliz- 

 ing measurement of the differing sedimentation rates 

 of molecules in solvent systems of known density. 

 Gofman and his associates (78, 79, 135) have used 

 a sodium chloride solution with a density of 1 .063 to 

 differentiate lipoproteins. These workers have also 

 introduced the "S f " nomenclature which is used to 

 describe the rates of flotation (varying S f values) of 

 the various lipoproteins in sodium chloride of density 

 of 1.063. Such rates of flotation are measured in 

 Svedberg units (Sf unit, io~ 13 cm g sec -1 dyne -1 ). 

 Apparently the Sf value is dependent on the density, 

 shape and size of the lipoprotein molecules (155). 



A plethora of terminology relating to the lipopro- 

 teins has evolved depending on methods of isolation 

 and identification (71, 78, 134). The subdivisions 

 sometimes have been rather arbitrary, yet certain 

 correlations have been made as, for example, be- 

 tween the ultracentrifugal and electrophoretic 

 behavior of the lipoproteins. It has been demon- 

 strated that there are two major groups of lipopro- 

 teins (three if chylomicrons are included) in human 

 plasma: /) high-density lipoproteins (density > 1.063), 

 or a-lipoprotein by virtue of their electrophoretic 

 mobility; 2) low-density (< 1.063) or /3-lipoproteins. 

 The latter (< 1.063) include the classes Sf 0-400 of 

 Gofman (78). The chylomicrons (density 0.94; see 

 above) have virtually no electrophoretic mobility, 

 but exhibit no definite line of demarcation from the 

 Sf 400 low-density lipoproteins, and their S f value 

 may reach 40,000. Studies of the protein moiety of 

 the lipoproteins have yielded information which 

 may further help characterize the ultracentrifugally 

 separated fractions. Information is available (71) 



