304 TRANSACTIONS OP SECTION 1. 



other forms. This is not the case, in fact the relationship is in the opposite 

 direction — the increase of creatin being accompanied rather by an increase in 

 ' other nitrogen.' 



On the other hand, I then failed to appreciate the possibility that the increase 

 in the creatin might be the result of a failure of its metabolism in some other 

 direction. 



Neither Folin nor any other worker has found an immediate increase in the 

 nitrogen excretion after the administration of creatin, and it thus seems un- 

 likely that any metabolic change occurs in it when about to he, excreted. But 

 its metabolism may be in the process of anabolism, and I shall later adduce 

 evidence that creatin may be used in the building up of the muscle material, 

 e.g., as a source of the guanidin in arginin. 



But whether the increased excretion of creatin in fasting is due to its 

 liberation from muscle substance as it breaks down (Myers and Fine), or to its 

 being a product of the disintegration of muscle substance (Folin), or to there 

 being a failure to resynthesise the creatin into muscle substance, the amount 

 of creatin in the urine will indicate the amount of muscle disintegrated and not 

 resynthesised, i.e., the actual break-down of mvscle. 



Three conditions may occur in the course of a fast : 



1. The break-down may involve not only muscle but also the proteins in other 

 tissues of the body. 



2. It may involve muscle almost exclusively. 



3. It may involve muscle, but the nitrogenous constituents may be used for 

 the repair of other tissues, as is so well seen in the fasting salmon, where 

 materials from the muscles are transported to and laid down in the growing 

 ovary. 



The first condition occurs in the early days of a fast, especially in well-fed 

 animals where the liver and other organs are rapidly losing weight. 



The third condition appears later in a fast when all surplus protein has been 

 metabolised, and when the organs essential to life have to be kept going at the 

 expense of the muscles. 



The muscles of the goose or duck contain about 0-134 per cent, of nitrogen 

 in creatin and 3-6 per cent, altogether. Henc-e, in the break-down of muscle, 

 one part of nitrogen must be in creatin for twenty-seven parts of total nitrogen. 



If the nitrogen of the urine is in this proportion, it is muscle tissue which 

 is bearing the brunt of the disintegration due to fasting. 



If the total nitrogen is above this proportion to the creatin nitrogen, 

 the protein-rich tissues other than muscle are taking their share in the cata- 

 bolic process. If the creatin nitrogen is above this proportion, then the con- 

 clusion seems inevitable that the nitrogen of the proteins of muscle is being 

 retained and used for the maintenance of non-muscular tissues. This method I 

 applied to the study of the metabolism in the course of fasting in geese and 

 ducks, and showed how it gave direct information of the condition of the ex- 

 changes in the body. 



Its application to the study of the progress of protein metabolism in fasts 

 in man and other mammals does not necessitate the adoption of any theory of the 

 relationship of creatin to creatinin. 



Folin's most recent view26 of the sources of th-ese two siibstances is that 

 creatinin represents the ordinary wear and tear of muscle, but that when 

 muscle tissue dies the creatin is set free as a post-mortem product, and that 

 in times of stress, e.g., in fe.ver, fasting, etc., the break-down into creatinin is 

 accompanied by a break-down into creatin. He even admits the possible conver- 

 sion of small amounts of creatin to creatinin and vice versa. 



Accepting this conception, it is manifest that the creatinin and creatin 

 excretion should in the mammal give the same index of the course of metabolism 

 in fasting, as the excretion of creatin alone does in the bird. This I illustrated 

 in 1910 by applying the method to the study of several recorded facts in man. 



Creatin as an Anabolite. 



The evidence as to whether creatin is a possible anabolite, whether it can 

 be used for the reconstruction of muscle substances, may now be considered. 

 It was Folin who first suggested that it may act in this way, or, as he put 



