CREATINE AND CREATININE 77 



As bearing on the function of the liver in creatinine metabolism 

 the experiments of Gottlieb and Stangassinger [1907; 1908, I, 2] 

 must be mentioned. They concluded that liver extract dehydrates 

 creatine to creatinine and then decomposes it further ; these changes 

 may be brought about by autolysis, and creatinine is also formed by 

 perfusing the surviving liver with creatine. Mellanby [1908] criticised 

 the autolytic experiments and considered that in them the destruction 

 of creatine was due to bacteria. 



Rothmann [1908] and van Hoogenhuyze and Verploegh [1908] 

 supported Gottlieb and Stangassinger, but Beker[i9i3] agrees with 

 Mellanby that the destruction of creatine was due to bacteria. As 

 pointed out on page 10 it is very difficult to ensure sterility in auto- 

 lysis. Gottlieb and Stangassinger's perfusion experiments, on the 

 other hand, are held by Beker to prove that the liver can dehydrate 

 creatine to creatinine. 



Possible Precursors of Creatine. 



The oldest attempts to find a precursor of creatine were directed 

 to showing that creatine can be formed in the organism from glyco- 

 cyamine ; Jaffe [1906] and Dorner [1907] adduced evidence in support 

 of this, but since the transformation is a simple methylation, for which 

 there are several examples in animal metabolism, and since glyco- 

 cyamine does not occur in nature, the formation of creatine from this 

 substance would hardly be a physiological process (see further the 

 next section on glycocyamine). Suggestions as to the formation of 

 creatine from muscle protein have been made by Seemann [1907] and 

 by Urano [1907]. According to Antonoff [1906-7] certain bacteria 

 (e.g. B. coli} can form from peptone a substance giving Weyl's re- 

 action (creatinine?). The one known protein constituent containing 

 a guanidine grouping is arginine, but neither van Hoogenhuyze and 

 Verploegh [1905] nor Jaffe [1906] could obtain creatine from arginine 

 in feeding experiments or by subcutaneous injection. The whole of 

 the administered arginine was excreted in the urine. Dakin [1907] 

 has shown that creatine is not affected by arginase from the liver. 

 Lately, however, Inouye [1912] has observed a small formation of 

 creatine from arginine by liver extract and when arginine is perfused 

 through the isolated liver. Finally Riesser [1913], in a paper which 

 contains a useful review of the whole problem, has described experi- 

 ments in which creatine appears to be formed from choline and from 

 betaine (see also pp. 62 and 42). By injecting these substances 

 into rabbits, he increased the creatine content of the muscle, which is 



