76 THE SIMPLER NATURAL BASES 



lively. This may be connected with the post partum excretion of 

 creatine. 



Attempts to increase the muscular creatine or urinary creatinine 

 by giving creatine by the mouth have not been very successful, perhaps 

 because of bacterial action in the intestine. Thus van Hoogenhuyze 

 and Verploegh [1908] found only slightly more creatinine in the urine 

 after taking 2 grm. of creatine. -The destruction of creatine by 

 bacteria has been studied by von Jaksch [1881], Vandevelde [1884], 

 and particularly by Twort and Mellanby [1912]. Ackermann [1913] 

 has shown that in putrefaction creatinine is not broken up like creatine, 

 but is changed to N-methylhydantoin. 



/NH . CO /NH . CO 



HN : C/ I + H 2 O = OC/ + NH 3 . 



\N CH 2 \N CH 2 



CH 3 CH :J 



When creatine was administered subcutaneously or intravenously, 

 however, a certain amount of direct evidence of its conversion to 

 creatinine has been obtained in rabbits [Pekelharing and van Hoogen- 

 huyze, 1910] and in dogs [Lefmann, 1908]. Recently Myers and Fine 

 [^S* 3] have shown that of injected creatine 5 per cent, appeared in 

 the muscles in rabbits; 25-80 per cent, appears in the urine as such, 

 and 2-10 per cent, as creatinine. Injected creatinine also causes a 

 slight increase of muscular creatine. 



Assuming the conversion of creatine to creatinine, we may next 

 inquire where this change takes place. Experiments on dogs, in 

 which the liver was put out of action by an Eck's fistula, have not 

 proved that the liver has any important function in creatinine metabolism 

 [London and Boljarski, 1909; Foster and Fisher, 1911 ; Towles and 

 Voegtlin, 1911]. The last-named authors found that creatine, given 

 to dogs, increases the creatinine output, but that putting the liver out 

 of action made very little difference. Paton and Mackie [1912], from 

 experiments on birds, likewise consider that the liver plays no part 

 in the conversion of creatine into creatinine. The appearance of crea- 

 tine in the urine in hepatic disease may suggest incomplete dehydra- 

 tion to creatinine in the liver, but the formation of creatine might be 

 increased through the disturbance of the carbohydrate metabolism, 

 resulting from damage to the liver. When the supply of carbohydrates 

 in the body is insufficient (in fasting, in diabetes mellitus and in 

 phloridzin glycosuria) the necessary energy must be obtained from 

 another source, and this latter process may be accompanied by in- 

 creased formation of creatine. 



