THE METABOLISM OF PROTEIN 627 



probably effected by many of the tissues of the body and certainly by 

 the blood, the active agency in all cases being no doubt an enzyme. That 

 the blood contains such an enzyme is indicated by the fact that creatine 

 is transformed to creatinine by blood serum more quickly than it is 

 when merely dissolved in water. Even heated blood serum possesses 

 some of this power. The liver also probably brings about the transfor- 

 mation, as has been shown by perfusion experiments, and by the fact 

 that in cases of phosphorus or hydrazine poisoning creatine displaces 

 creatinine in the urine. 



The problem therefore narrows itself down to the question of the 

 origin of creatine. In the light of chemical knowledge there are several 

 precursors from which creatine might be formed. One, for example, is 

 arginine, which it will be remembered is guanidine-amino-valerianic acid 

 (see page 605). By oxidation this might become changed into guani- 

 dine-amino-acetic acid, which by methylation would then be changed into 

 creatine. That such a process of methylation may actually occur in the 

 animal body is definitely known, for it happens when such substances as 

 pyridine or naphthalene are given with the food. They appear in the 

 urine as methyl derivatives. The possibility of the derivation of creatine 

 from arginine is not, however, borne out by the result of the injection of 

 arginine, for such injection does not increase the creatinine in the urine. 

 The closely related substance, guanidine-acetic acid, when fed to animals 

 (rabbits) does cause a slight increase in the excretion of creatine (Jaffe), 

 and also, it is said, an increase in the creatine content of the muscle. 

 Even in this case, however, by far the largest proportion of the admin- 

 istered guanidine-acetic acid is excreted in the urine unchanged. 



The large percentage of creatine in muscle tissue leads one to expect 

 that some relationship must exist between muscular metabolism and the 

 amount of creatine present either as such in the muscles or as creatinine 

 in the urine. Regarding the latter point it is definitely established that 

 muscular exercise leads to no increase in the creatinine excretion, al- 

 though it is said that an increase occurs following a tonic contraction 

 of the muscles. With regard to the creatinine in the muscles, no definite 

 results indicating that muscular metabolism changes its amount are on 

 record. In the light of the fact already stated regarding the presence 

 of creatine in other organs than the muscles, it seems probable that the 

 substance has really little to do with muscular contraction as such, but 

 rather is concerned in some way in the formative metabolism of the cell, 

 with its general growth or maintenance. Indeed, it is a question whether 

 creatine is an actual constituent of the living tissue. It may rather, as 

 has been suggested by Folin, be a postmortem product, represented dur- 

 ing life by creatinine. 



