CREATINE AND CREATININE 73 



Sullivan [1911] creatinine (and possibly also creatine) occurs in 

 wheat, rye, clover and other crops, whence it finds its way into culti- 

 vated soils, from which it was isolated in the crystalline condition by 

 Shorey [1912]. According to Skinner [1912] creatine and crea- 

 tinine have a beneficial effect on plant growth. 



Metabolism. 



The close chemical relationship between creatine and creatinine 

 already suggested to Liebig that the former substance is converted 

 in the animal organism into the latter and is then excreted in the 

 urine. This view as to a genetic relationship between the two sub- 

 stances was rejected by Folin, whose colorimetric estimation first 

 made accurate investigation possible. He [1905, i] was the first to 

 show that on a creatinine free diet the amount of creatinine excreted 

 in the urine is remarkably constant for any given individual, and this 

 important result was soon confirmed by various investigators, e.g. Koch 

 [1905], van Hoogenhuyze and Verploegh [1905], Closson [1906], af 

 Klercker [ 1 907], Shaffer [ 1 908], Levene and Kristeller [ 1 909]. Various 

 authors give slightly different limits for the daily output ; thus Folin 

 gave i '3-17 grm. for a man of 70 kilos., i.e. 19-24 mg. per kilo, of 

 body weight, Closson 15-19 mg. and Shaffer 19-30 mg. of creatinine 

 per kilo, per diem. 



On this constancy of the creatinine output in the individual Folin 

 [1905, 2] has based a theory of protein metabolism (see Cathcart's 

 monograph in this series, " Physiology of Protein Metabolism," pp. 94, 

 95, 98), according to which theory the creatinine excreted is a result 

 and measure of the "endogenous" catabolism of the tissues and is 

 independent of the " exogenous " catabolism and of the protein of the 

 diet. Creatinine given by the mouth is rapidly and almost quantita- 

 tively excreted in the urine as such and this exogenous creatinine of 

 the food is thus super-imposed on the constant endogenous amount. 

 Creatine, on the other hand, as Folin [1906] has shown, when given 

 by the mouth in moderate quantity, does not appear in the urine, 

 neither as such, nor as creatinine. This observation has also been 

 made by many other investigators, e.g. Czernecki [1905] and Plimmer, 

 Dick and Lieb [1909]; the latter authors found, for instance, that 

 creatine appeared in the urine after a daily dose of 2'5 grm. but not 

 after 2 - o grm. In children the power of assimilating creatine is much 

 smaller and even of doses of 0-3 grm. some appears in the urine, 

 super-imposed on that normally present [Krause, 1913]. 



In accordance with Folin's theory the amount of endogenous 



