78 ENZYMES 



vitro seems to begin, part of which time may be occupied in the develop- 

 ment of sufficient acidity to permit of autolysis, although Bradley's^^ 

 results indicate that it can be accounted for largely by the time re- 

 quired for proteolysis to proceed far enough to be detected by chemical 

 means. Dernby^'* finds that in several tissues studied, including 

 leucocytes, there are two intracellular proteases, one resembling pepsin 

 in carrying digestion only to the peptone stage and in requiring an 

 acid medium, optimum pH = 3.5; the other resembling ereptase, 

 splitting only peptones and peptids into amino-acids, with optimum 

 reaction pH = 7.8, and inhibited by acid reaction. Autolysis of tis- 

 sues proceeds furthest in a pH range between 5 and 6, presumably 

 because in this condition both enzymes can act. From these facts it 

 is evident that quantitative studies of rates of autolysis are valueless if the 

 H-ion Tconcentration is not taken into consider atio7i. 



The cleavage products resulting from tissue autolysis seem to 

 contain a much larger proportion of the nitrogen in the form of 

 ammonia and its compounds than is the case with simple tryptic 

 digestion, because of the presence of deaminizing enzymes which split 

 the NH2 groups out of the amino-acids and purines. According to 

 Bostock^^ the greater the acidity the less NH3 is formed. It is quite 

 probable that in tissue autolysis several intracellular enzymes are in 

 action which may not be present in pancreatic or gastric juice; for ex- 

 ample, in the liver is an enzyme, arginase, which splits the urea radical 

 out of the arginine of the proteins (Kossel and Dakin^''), and the 

 enzymes which disintegrate purines are also absent from the digestive 

 juices. On the whole, however, the products are quite similar to those 

 obtained by tryptic digestion. To give a concrete example, Dakin^^ 

 detected in the products of autolysis by the kidney in acid solution, the 

 following substances: Ammonia, alanine, a-aminovalcrianic acid, leu- 

 cine, a-pyrollidine carboxylic acid, phenylalanine, tyrosine, lysine, histi- 

 dine, cystine, hypoxanthine, and indole derivatives, including probably 

 tryptophane.^^ The cleavage of simple peptids by different tissues 

 shows characteristic differences, the distribution of the enzj-me which 

 splits glycyl-tryptophane having been most studied. During life the 

 cells retain this enzyme, and hence it appears in the body fluids only 

 when the tissues are being rapidly disintegrated (Mandelbaum).^^ 



During autolysis the changes are by no means limited to the pro- 

 teins. Glycogen is split into glucose very early, and the sugar under- 

 goes further changes. Fats are also split by the lipase, fatty acids 



" Jour, liiol. Chcm., 191G (25), 3G3. 

 !■• .lour. Biol. Chem., 1918 (35), 179. 

 >5 Biochein. Jour., 1912 (6), 388. 

 >6 Zeit. physiol. Chcm., 1901 (42), 181. 

 iMour. of PhysioloKY 1903 (30), 84. 



18 The results of autolysis by (iilTcrcnt tissues are said to be quite dissimilar. 

 See Kashi\val)ara, Zeit. i)hysiol. Chcm., 1913 (85), IGl. 

 '9 Miinch. med. Woch., 1914 (01), 401. 



