590 THE URINE [CH. XXXIX. 



the blood-stream does not cause any increase in urea formation ; the 

 creatine injected is almost wholly excreted unchanged. 



It also is not converted into creatinine, although it has been 

 generally assumed that this conversion does occur. The transforma- 

 tion of creatine into creatinine is shown in the following equation : 



C 4 H 9 N 3 O 2 - H 2 O = C 4 H 7 N 3 O. 



[Creatine.] [Water.] [Creatinine.] 



Kecent researches have entirely failed to substantiate the view 

 that the urinary creatinine originates from the muscular creatine. 

 If creatine (an innocuous neutral substance) were converted by the 

 loss of water in the muscles into creatinine (a strongly basic 

 substance), it would be contrary to all that is known of the chemical 

 changes that occur in the body. 



Creatinine is present in the urine; it is, in fact, next to urea the 

 most abundant nitrogenous substance found there. Amid all the 

 inconstancies of urinary composition, it appears to be the substance 

 most constant in amount, diet and exercise having no effect on it. 

 Folin's view, that its amount is a criterion of the extent of 

 endogenous nitrogenous metabolism, has steadily gained ground, and 

 the work of the past few years has shown that the liver and not the 

 muscles is the seat of its formation. Some observers have supposed 

 that certain tissue enzymes, termed creatase and creatinase, are agents 

 in its formation and destruction ; others have failed to discover the 

 presence of these enzymes in the liver. On this and on other points 

 there are differences of opinion, but without discussing the pros and 

 cons of minor details, the following view of Mellanby may be taken 

 as a working hypothesis of the metabolic history of the substances 

 in question. Mellanby took as his starting-point an investigation of 

 the contradictory data relating to the proportion of creatine and 

 creatinine in muscle, and by improved methods showed that 

 creatinine is never present in muscle at all, even after prolonged 

 muscular work. He then studied in the developing bird the amount 

 of creatine at different stages, and found that it is entirely absent in 

 the chick's musculature up to the twelfth day of incubation ; after 

 this date the liver and the muscular creatine develop pari passu. 

 After hatching, the liver still continues to grow rapidly, and the 

 creatine percentage in the muscles increases also, although the 

 development in the size of the muscles occurs very slowly. This 

 and other experiments on the injection of creatine and creatinine 

 into the blood-stream finally led Mellanby to the following hypo- 

 thesis : Certain products of protein katabolism, the nature of which 

 is uncertain, are carried by the blood to the liver, and from these the 

 liver forms creatinine ; this is transported to the muscles and there 

 stored as creatine; when the muscles are saturated with creatine, 



