9 o 4 METABOLISM. 
metabolism, even at a time "when the tissues are temporarily supplied with 
circulating proteid from the blood of a well-nourished animal. 
That a continuance of liberal proteid diet does produce an increased growth 
of muscular tissue, may also be looked upon as extremely probable, from the 
daily experience of athletes. As is well known, the diet upon which training 
is chiefly carried out consists very largely of proteid matter, the proteids of the 
food being in much larger proportion to the fats and carbohydrates than in the 
normal diet of untrained persons. It would appear likely that this, which is 
the result of the experience of many generations of trainers, must have a 
physiological basis, and that the effect of such excess of proteid in the diet 
must in itself not only cause an increase of the proteid metabolism, but also 
lead to the formation of actual tissue proteid. Under ordinary circumstances, 
however, whether the proteid which passes to the muscles is actually built up 
into then tissue, or whether it is simply included in the interstices of the 
living substance, it is not stored there for long ; for it is found, after a meal 
containing much proteid, that within a few hours practically the whole of the 
proteid which has been absorbed is removed in the form of urea. 
That the change in proteid which results in the formation of urea 
must primarily occur within the muscles, within which, as we have 
seen, the greater part of the oxidations of the body occur, there can be very 
little doubt. But there has always been this difficulty in connection 
with the question, that although urea is the ultimate product of proteid 
metabolism, the muscles practically contain either no urea or only a 
very small amount. An exception is, it is true, found in certain animals, 
e.g. the Elasmobranch fishes, the muscles of which contain a considerable 
amount of urea, But this is not the case with most animals, and it 
cannot be supposed that urea is formed to any appreciable amount in 
the muscles, especially since we know that by far the greatest amount 
is actually formed in the liver. 
What precursor, therefore, of urea is formed in the muscles from the 
proteid which is metabolised within them ? The nitrogenous substance 
which could best be supposed to be produced from the metabolism of pro- 
teids, is creatine, since this is the one foimcl in largest amount within 
the muscles ; and it is natural to suppose that creatine, which is capable 
of being converted in the laboratory without any great difficulty into 
urea and sarcosine, might be the immediate precursor of urea. It is, 
however, found that if creatine is injected into the blood or subcutane- 
ously, or if it is taken with food, and thus absorbed into the blood, it 
does not become converted into urea, but is found in the urine as 
creatinine; and we cannot therefore suppose that the creatine of the 
muscles is absorbed by the blood, and carried by that fluid to the liver, 
and there converted into urea, since we find that creatine added to the 
blood does not become so converted. 
"Without ignoring the possibility that the creatine which is found in 
muscle may still be a preliminary stage in the transformation of 
proteid into urea, we must look for other products of nitrogenous 
metabolism passing from the muscles which, whether derived immedi- 
ately from the proteid or indirectly from it through creatine, may be 
supposed to be the real precursors of urea. As a matter of fact, such 
products are found in the form of ammonia salts. It was noticed by 
Schondorff, in the experiments already quoted, that in cases in which 
the blood of a fasting animal was sent through the limbs only of a well- 
1 Stadeler and Frerichs, J&urn. f. praM. Chan., Leipzig, 1S58, Bd. lxxiii. S. 48. 
