58 ENZYMES 



beisis may explain the manner in which chemical changes are believed 

 to occur in the cells and fluids of the body : " 



In the intestines fat is split by lipase into a mixture of fat, fatty acid, and 

 glj'cerol; but as the fatty acid and glycerol are diffusible, while the fat is not, 

 they are separated from the fat by absorption into the wall of the intestine. 

 Hence an equilibrium is not reached in the intestine, so the splitting continues 

 until practically all tiie fat has been decomposed and the products absorbed. 

 When this mixture of fatty acid and glycerol first enters the epithelial cells lining 

 the intestines there is no equilibrium, for there is no fat absorbed with them as 

 such. Therefore the lipase, which Kastle and Loevenhart showed was present 

 in these cells, sets about to establish equilibrium bj' combining them. As a result 

 we have in the cell a mixture of fat, fatty acid, and glycerol, which will attain 

 equilibrium only when new additions of the two last substances cease to enter 

 the cell. Now another factor also appears, for on the other side of the cell is 

 the tissue fluid, containing relatively little fatty acid and. glycerol. Into this the 

 diffusible contents of the cell v.'ill tend to pass to establish an osmotic e(iuilibrium, 

 which is quite independent of the chemical equilibrium. This abstraction of part 

 of the cell contents tends to again overthrow chemical equilibrium, there now being 

 an excess of fat in the cell. Of course, the lipase will, under this condition, reverse 

 its action and split the fat it has just built into fatty acid and glycerol. It is 

 evident that these processes are all going on together, and that, as the composi- 

 tion of the contents of the intestines and of tlie blood-vessels varies, the direction 

 of the enzyme action will also vary. In the blood-serum, and also in the lym- 

 phatic fluid, there is more lipase, which will unite part of the fatty acid and 

 glycerol, and by removing them from the fluid abotit the cells favor osmotic diffu- 

 sion from the intestinal epithelitmi, thus facilitating absorption. 



Quite similar must be the process tliat takes place in the tissue cells through- 

 out the body. In the blood-serum batliing the cells is a mixture of fat and its 

 constituents, probably nearly in equilibrium, since lipase accompanies them. If the 

 diffusible substances enter a cell containing lipase, e. g., a liver cell, the process 

 of building and splitting will be quite the same as in the intestinal epitlielium. 

 The only difference is that here the fatty acid may be removed from the cell by 

 being utilized by oxidation or some other chemical transformation.! i 



To summarize, it may be stated that throughout the body there is 

 constantly taking- place both splitting and building of fat. Fat enters 

 the cells, leaves them, and is utilized only in the form of its acid and 

 alcohol, never as the fat itself. Fat constitutes a resting stage in its 

 own metabolism. 



If proteolytic enzymes also act reversibly, then the phenomena of 

 protein metabolism are similarly explained, for there is no doubt 

 that every cell and body fluid contains proteolytic enzymes. 



All metabolism, then, may be considered as a continuous attempt at 

 establishment of equilibrium bij enzymes, perpetuated by prevention 

 of attainment of actual equilibrium through destruction of some of 

 the participating substances by oxidation or other chemical processes, 



10 See Loevenhart, Amer. Jour, of Physiol., 1002 (G), 331; Wells, Journal 

 Amer. Med. Assoc, 1902 (38), 220. The discrepancies between tiie action of 

 lipase in the tissties and in vitro are well explained liy Taylor, Jour. Biol. Chem., 

 1906 (2), 103. 



11 Bradley (.Tour. Biol. Chem., 1910 (8), 2r)l; 1913 (13). 407-439) calls atten- 

 tion to tlic great conc(>ntration necessary for fat synthesis by lipase in vitro, 

 and tlie lack of correspondence between Die amount of fat and of lipase in various 

 tissues, questioning tlie importance of lipase for fat synthesis in the living tissues 

 as well as the significance of reversed enzyme reaction for biological processes in 

 general. 



