302 TRANSACTIONS OF SECTION I. 



In a man of 65 kilos, the skeletal muscles weigh about 30 kilos, with, say 

 0-3 per cent, of creatin, in all some 90 grms. ' 



If anything like 1 grm. of creatin be given it tends to appear as such 

 in the urine. 



The taking of even a moderate amount of flesh leads to the appearance of 

 creatin in the urine and although, as Orr and Burns 22 have shown, the creatin 

 is not necessarily all derived from the creatin of the flesh but probably from 

 some other precursor, nevertheless a considerable amount comes directly from 

 creatin. Evidently the power which the body possesses of dealino- with 

 creatin is very limited. " 



At present I do not intend to discuss the question of the possible conversion 

 or non-conversion of creatin to creatinin. It has been an unfortunate battle 

 because it has drawn attention from the much more important question — whai 

 is the significance of creatin? — the question on which I have tried to throw a 

 fresh light in considering its relationship to guanidin, but one which has to be 

 further prosecuted in order to decide whether creatin is simply a waste product 

 on the way to excretion or whether it may be used in the body. 



To me it seems that these questions may best be solved by their study in 

 animals in which they are least complicated by the creatin-creatinin controversy. 

 Fortunately in birds, as was long ago shown by Meissner. we have a group of 

 animals which excrete creatin as an end product and only at most traces of 

 creatinin. This I confirmed in 1910 ^^ and it has been further confirmed by 

 Thompson. Just as their power of changing uric acid to urea is small so that 

 most of their nitrogen comes away in the first form, so their power of changing 

 creatin to creatinin — if it is possessed by any animals — is negligible. 



The results then obtained seemed to show that creatin injected subcu- 

 taneously does not undergo any change in the avian body, but that it is 

 excreted as such. In three experiments, creatin injected under the skin 

 appeared in the urine to the extent of 91 per cent., 109 per cent., 83 per 

 cent. 'Such observations do not, however, prove that the creatin formed in the 

 ordinary course of metabolism is all excreted in this form. 



Since creatin is at least ten times more abundant in muscle than in any 

 other tissue of the body, and since muscle so greatly exceeds all other tissues 

 in bulk, muscle must be considered the source of urinary creatin. 



The amount of creatin daily excreted must be the result of the liberation 

 of so much creatin from the miiecles, and since the amount of creatin in muscle 

 is so constant, this liberation must be covered by a corresponding formation, or 

 by a corresponding decrease in the bulk of muscle. 



It is well known that in fasting; mammals creatin appears in the urine. 

 and that in the fasting condition in man the combined excretion of creatin and 

 creatinin shows a comparatively small change in spite of the decrease in the 

 rate of protein catabolism as indicated by the excretion of total nitrogen. 

 In the rabbit on the other hand Dorner's results show an increased total 

 protein catabolism with an enormous increase of the excretion of creatin and 

 creatinin due almost entirely to the creatin. 



In geese and ducks I found that there is a rise in the excretion of creatin 

 during fasting which varies with the condition of nutrition of the bird, being 

 small where the nutrition is good at the beorinning of the fast and larger where 

 the animal has been on a low diet and is thin before the fast starts. Thus in 

 a young, well-fed goose during a fast of three days there was practically no 

 change in the excretion of creatin, while in a poorly nourished bird fed on 

 maize the creatin excretion on the second day of the fast had increased 

 sevenfold. 



Myers and Fine ^^ from their observation.5 upon fastingr doers come to tho 

 conclusion that the increased amount of creatin exeereted during a fast is all 

 derived from the creatin which was in the flesh at the commencement of thp 

 fast. They find in short fasts a slight increai^e in the creatin content of 

 muscle and in longer fasts a decrease. A series of unpublished analyses made 

 for me by Cathcart of the muscles of the salmon kelts and of feeding 

 salmon show that after the prolonojed fast of many months the creatin is 

 increased in relation to the total nitrogen of the muscle. 



