NITROGENOUS WASTE-PRODUCTS 547 



tissues only. The daily output of creatinine, although so constant 

 in a given individual, varies in different individuals with the weight, 

 and more especially with the degree of muscular development. Obese 

 persons, notwithstanding their high body-weight, have a low creatinine 

 output, wliile comparatively lean persons, who by virtue of muscular 

 development have a like weight, exhibit a high creatinine output. 

 It is true that muscular work on a normal diet does not increase the 

 creatinine output, but then we have seen that on a normal mixed diet 

 the muscles do not derive their energy from the metabolism of their 

 own substance (protein) but from the oxidation of carbohydrates. 

 When, however, muscular work is performed during starvation, the 

 creatinine output is definitely increased. In other words the actual 

 destruction of muscular tissue results in an increase of creatinine 

 excretion. 



It appears very probable that the normal products of the disinte- 

 gration of tissue-protein are similar to or identical with the substrates 

 out of which tissue-protein is synthesized, namely, the amino-acids, 

 for we have seen that the process of tissue-synthesis is a balanced 

 reaction which is retarded by its products, and this can only be true 

 if the products of the synthesis break down, in the first place, into 

 the substances which form the substrates of the forward reaction. The 

 amino-acids which are thus set free are cast into the general stock of 

 circulatory and storage amino-acids, undergo their share of exogenous 

 metabolism or deaminization, and participate with the ingested amino- 

 acids arising from the foodstuffs in determining the Nutrient-level of 

 the tissue-fluids. If the nutrient-level falls, as in starvation, the amino- 

 acids of tissue origin form a large proportion of the whole mass of cir- 

 culating amino-acids, and their deaminization results in a continual 

 drainage which, in turn, results in a steady loss of tissue-substance. 

 There must, in fact, be an endogenous or tissue-source of urea, for 

 otherwise urea excretion would ultimately fall to zero in starvation, 

 which it never does. In fact, even in starvation the urea output still 

 exceeds very decidedly the creatinine output. On the other hand, if 

 the tissues must use their own substance for the performance of 

 external work, at any rate in muscular tissues, the breakdown of the 

 protein or of amino-acids resulting therefrom takes another course, 

 with the production of creatinine. The effect of this must be to initiate 

 a process analogous to repair or Regeneration by the resynthesis of 

 the lost tissue-proteins from amino-acids. 



Creatine is not a normal constituent of the urine of adult men and, 

 as has been stated above, the ingestion of creatine leads to no increase 

 in the creatinine output, nor does it lead to the appearance of any. 

 creatine in the urine. In the urine of women, on the contrary, creatine 

 is found during menstruation and after delivery, and the ingestion 

 of creatine leads to the appearance of a small proportion of the creatine 

 in the urine. In the urine of children creatine is a regular constituent. 

 According to Krause it disappears from the urine of boys at about five 



