52 ENZYMES 



that this is accompUshed by enzymes, presumably by a reversal of 

 their action in the establishment of equilibrium. Abderhalden^^ has 

 obtained some evidence of protein formation in mixtures of amino 

 acids derived from autolyzing tissue when acted upon by ferment- 

 containing extracts of the same tissue. Taylor^^ was able to synthesize 

 protamin, one of the simplest proteins, by the action of trypsin upon 

 its cleavage products, and it has been found that the addition of 

 proteolytic enzymes to solutions of pure albumose leads to the forma- 

 tion of a jelly-like, insoluble protein substance, " plastein," which seems 

 to be the effect of a reversed action on the part of the enzymes. ^^ 

 Another well known synthetic action that seems to be due to reversible 

 ferment action is the formation of hippuric acid from benzoic acid and 

 glycine in the Iddney; the formation of glucose into glycogen and its 

 reformation 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 problems 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:^^ 



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

 glycerol; 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 the fat has been decomposed and the products absorbed. 

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

 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 by 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 will tend to pass to establish an osmotic equilibrium, 

 which is quite independent of the chemical equilibrium. Tliis 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, ex- 

 hibit the reverse 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 the blood-vessels varies, the direction 

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

 phatic fluid, there is also lipasC; which will unite part of the fatty acid and glycerol, 



'2 Fenuoritforschung, 1914 (1), 47. 



" Jour. Biol. Chem., 1909 (5), 381. 



1^ See Michcli, Arch. ital. biol, 190G (46), 185;Levene and Van Slvke, Biochem. 

 Zeit, 1908 (13), 458; Taylor, Jour. Biol Chem., 1909 (5), 399; Gav and Robert- 

 son, ibid. 1912 (12), 233; Alxlerhalden, IVrnientforsch., 1914 (1), 47; v. Knaffl- 

 Lenz and Pick, Arcli. exp. Path., 1913 (71), 29(), 407. 



'5 See Loevenhart, Amer. Jour, of Fliysiol., 1902 (0), 331; Wells, Journal 

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

 lipase in the tissues and in vitro are well explained by Taylor, Jour. Biol. Chem., 

 1906 (2), 103. 



