Apbil 9, 1909] 



SCIENCE 



587 



these compounds in autolysis led him to 

 postulate that they can undergo a series of 

 enzymatic transformations in the body, as 

 follows: (1) Oreatin can be formed in the 

 autolysis of muscles and other organs. (2) 

 Preformed or added creatin can be converted 

 by enzymatic means into creatinin during 

 autolysis. (3) In the progress of autolysis 

 both of the compounds are destroyed by appro- 

 priate enzymes, creatase and creatinase. (4) 

 The interaction of these processes affords a 

 complicated curve for the creatin- and cre- 

 atinin-content of autolyzing tissue extracts, 

 since formation, conversion, and destruction 

 may simultaneously go on. The behavior of 

 creatin in the autolysis of different organs 

 will vary according to the preponderance of 

 one or the other of these different fermentative 

 activities. 



When we take into account the variations 

 in the occurrence of these intracellular en- 

 zymes in the different tissues and note that the 

 actual amount of creatin or creatinin found 

 in an experiment at any moment represents 

 the equilibrium point for a number of inter- 

 dependent reactions the complexity of the situ- 

 ations becomes apparent. Truly a " bewilder- 

 ing array " of enzymatic processes, as Mel- 

 lanby intimates in his severe critique of Gott- 

 lieb's work. Mellanby attributes the disap- 

 pearance of creatin and creatinin to contam- 

 inating bacterial influences in these experi- 

 ments; and he characterizes the conversion 

 experiments as unconvincing because of the 

 inappropriate analytical manipulations. Mel- 

 lanby himself reports uniformly negative re- 

 sults on the behavior of creatin in autolysis. 

 The repetition of these researches on the au- 

 tolysis of tissues under more satisfactory con- 

 ditions of control has, however, induced a 

 number of investigators (van Hoogenhuyze 

 and Verploegh, '08; Eothmann; Lefmann) to 

 maintain the essential importance of endo- 

 enzymes in the metabolism of the com.pounds 

 under discussion. Dakin has shown that 

 arginase will not act upon creatin. The the- 

 ory of the enzymatic transformation of creatin 

 is comparable in many respects with accepted 

 ideas regarding the metabolism of purins and 

 other cellular products, and furnishes an 



attractive working hypothesis; it must, how- 

 ever, be admitted with reserve, if at all, until 

 it rests upon a more substantial basis than the 

 uncertain evidence of a color reaction. 



This brings us to the facts in regard to the 

 elimination of creatin and creatinin. The 

 normal urine of healthy individuals contains 

 no creatin whatever, or at most only traces. 

 Folin's well-known observations demonstrated 

 that the output of creatinin in an individual 

 is practically constant despite very wide ranges 

 of (creatinin-free) diet. This fact, now abun- 

 dantly verified in many laboratories, led to the 

 conclusion that the excreted endogenous cre- 

 atinin is the expression of the true tissue 

 katabolism, as distinguished from the exogen- 

 ous protein katabolism consisting of a series 

 of rapid hydrolytic cleavages resulting in the 

 elimination of protein-nitrogen as urea. As 

 might be expected, the output varies with the 

 bulk of the metabolic tissues of the body, 

 averaging about 15 to 20 milligrams per kilo- 

 gram of body weight. The attempt to con- 

 nect the excreted creatinin with tissue creatin 

 has brought to light an apparent independence 

 of these compounds in metabolism. Ingestion 

 of creatinin results in increased creatinin elim- 

 ination; but when creatin is fed to man or 

 animals the creatinin content of the urine is 

 scarcely altered, if at all (Folin, '06 ; Klercker ; 

 van Hoogenhuyze and Verploegh; Lefmann). 

 Observations by Lefmann also uphold this for 

 creatin introduced parenterally. It would ap- 

 pear, then, that creatin, when fed, is not con- 

 verted to any extent into creatinin in the body. 

 Furthermore, in distinction from creatinin, 

 the creatin of the diet reappears at best only 

 in small part as such in the urine. In the 

 noteworthy feeding experiments of Folin the 

 nitrogen of the creatin which disappeared was 

 in some cases assumed not to be recovered in 

 any form in the urine, especially where the 

 diet was deficient in protein. Folin has ad- 

 vanced the tentative hypothesis that creatin 

 may be one of those special products which 

 serve to maintain the nitrogen equilibrium 

 in the living tissues, but which do not easily 

 take part in the urea-forming process; hence 

 the muscle is found rich in creatin. When 

 the organism is daily supplied with an abun- 



