THE PRINCIPLES OF ENZYME ACTION 67 



found that the addition of proteolytic enzymes to solutions of 

 pure albumose leads to the formation of a jelly-like, insoluble 

 proteid substance, which seems to be the eifect of a reversed 

 action on the part of the enzymes. 1 Indeed, the question has 

 been raised whether the coagulating or " lab-ferment " (rennin) 

 of the stomach is anything more than the pepsin itself, acting 

 in a reverse direction. 2 Another well-known synthetic action 

 that seems to be due to reversible ferment action is the forma- 

 tion of hippuric acid from ben zoic acid and glycocoll in the 

 kidney ; the formation of glucose into glycogen and its reforma- 

 tion are also probably both accomplished by one and the same 

 enzyme acting reversibly. Other reversible reactions less 

 closely related to animal cells have also been described. 



The reversible nature of enzyme action explains many prob- 

 lems of metabolism, and makes the whole field much clearer. 

 The following consideration of the newer understanding of fat 

 metabolism on this basis may explain the manner in which 

 chemical changes are believed to occur in the cells and fluids 

 of the body : 3 



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

 glycerin ; but as the fatty acid and glycerin are diffusible, while the fat is 

 not, they are separated from the fat by absorption into the wall of the intes- 

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

 continues until practically all the fat has been decomposed and the products 

 absorbed. When this mixture of fatty acid and glycerin first enters the epi- 

 thelial cells lining the intestines there is no equilibrium, for there is no fat 

 absorbed with them as such. Therefore the lipase, which Kastle and Loeven- 

 hart showed was present in these cells, sets about to establish equilibrium by 

 combining them. As a result we have in the cell a mixture of fat, fatty acid, 

 and glycerin, 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 glycerin. Into this the diffusible contents of the cell will tend to pass 

 to establish an osmotic equilibrium, which is quite independent of the chem- 

 ical 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 glycerin. It is evident that these proc- 

 esses are all going on together, and that, as the composition of the contents of 

 the intestines and of the blood-vessels varies, the direction of the enzyme action 

 will also vary. In the blood-serum, and also in the lymphatic fluid, there is 

 more lipase, which will unite part of the fatty acid and glycerin, and by re- 

 moving them from the fluid about the cells favor osmotic diffusion from the 

 intestinal epithelium, thus facilitating absorption. 



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

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



1 Herzog, Zeit. f. physiol. Chem., 1903 (39), 305. 



2 The results of filtration experiments suggest that pepsin and rennin are 

 distinct substances (Levy, Jour. Infect. Diseases, 1905 (2), 1 ; also see Schmidt- 

 Nielsen, Zeit. physiol. Chem., 1906 (48), 92). 



3 See Loevenhart, Amer. Jour, of Physiol., 1902 (6), 331 ; Wells, Journal 

 Amer. Med. Assoc., 1902 (38), 220. 



