ON UREA AND ON NITROGENOUS METABOLISM. 459 



Meanwhile, we may state the conclusion at which we have provisionally 

 arrived, namely, that the nitrogenous metabolism of muscle probably 

 gives rise to kreatin, which, in some part of the body other than muscle, 

 is probably split up into urea, ready for excretion, and into sarcosin which 

 also, somewhere in the body, is further converted into urea. And bearing 

 in mind the large mass of the skeletal muscles, we may further conclude 

 that a large portion of the urea leaving the body by the urine is formed in 

 this way. 



399. We must not, however, leave this statement without referring to 

 a difficulty. Kreatinin, as we have seen, is so frequently found in urine as 

 to be regarded as a normal constituent, at all events, of human urine ; aftd 

 kreatinin is, as we have seen, the urinary form, so to speak, of kreatin ; the 

 one body easily changes into the other by the assumption or removal of 

 H 2 O. This suggests the question, Is not the kreatinin of urine the repre- 

 sentative of the kreatin of the muscles, which is thus exerted directly 

 without undergoing the change into urea just discussed ? In answer to 

 this we may say, in the first place, that the quantity of kreatinin in the 

 urine, though variable, is small ; we may put the average at about 1 grm. 

 in twenty-four hours. Now, muscle contains from 0.2 to 0.4 per cent, of 

 kreatin ; and this, taking the total muscle of the body (to say nothing of 

 other sources of kreatin, which we shall mention presently) at about 30 

 kilos, would give 60 to 120 grms. of kreatin as present in the muscles of the 

 body at any one moment. We can hardly suppose that the metabolism of 

 muscle is so slow as out of this stock only to provide the 1 grm. of kreat- 

 inin in twenty-four hours. Moreover, the kreatin in urine vanishes during 

 starvation, is very markedly increased by a diet of flesh which contains 

 kreatin, and is not increased either by muscular exercise (which, however, 

 would only indirectly affect nitrogenous metabolism of muscle), or by such 

 conditions, fever, for instance, as notably increase the urea of urine by in- 

 creasing the nitrogenous metabolism of muscle. We infer, therefore, that 

 the normal presence of kreatinin in urine is due to the direct administration 

 of kreatin present in a (normal) flesh diet, and has nothing to do with the 

 muscular metabolism of the individual who is secreting the kreatinin in his 

 urine. 



The fact, however, that the kreatin present in the muscle of the food and 

 absorbed from the alimentary canal does not undergo a change into urea, but 

 is excreted as kreatinin, that is, virtually as kreatin, warns us to be careful 

 in adopting the conclusion arrived at above, that the kreatin produced by 

 muscular metabolism in the living body is a conspicuous antecedent of the 

 urea of the urine. It is difficult to see why kreatin passing into the blood 

 of the capillaries of the muscle should be changed into urea, while that which 

 passes into the capillaries of the portal system is not ; for reasons which will 

 be apparent presently, we should rather expect that the latter being more 

 directly exposed to the influence of the liver would be more readily and 

 more completely converted than the former. Indeed, the question forces 

 itself upon us, Is kreatin, after all, the natural main product of the nitro- 

 genous metabolism of muscle? It is possible that in the normal metab- 

 olism of the living muscle the nitrogen leaves the muscular substance 

 and passes into the blo.od in another form, as some substance not kreatin, 

 and that it is as the muscle dies that kreatin is formed, just as the solid 

 myosin is unknown to living fibre but makes its appearance in a dying 

 one? We have no positive evidence, however, that this is so, and, mean- 

 while, may continue to suppose that kreatin is formed, and that, in conse- 

 quence, kreatin is a conspicuous antecedent of the urea of the urine ; but 

 we must not regard this as proved. 



