NITROGENOUS WASTE-PRODUCTS 545 



Now it has been shown by Macleod and Haskins that there is an 

 equilibrium in aqueous solutions between ammonium carbonate and 

 Ammonium Carbamate, so that if the ammonium carbamate is removed 

 by transformation into urea a continuous renewal of the ammonium 

 carbamate is to be expected, and consequently a quantitative conversion 

 of the ammonium carbonate into urea. The formation of ammonium 

 carbamate as an intermediate product in the synthesis of urea in the 

 body is shown by the fact that if alkalies be administered to animals 

 in considerable quantity carbamates appear in abundance in the urine. 

 A direct conversion of ammonium carbamate into urea has been 

 accomplished by Drechsel by simply passing an alternating current 

 through its solution, i. e., by alternate oxidation and reduction which 

 is, of course, equivalent to dehydration. We may infer, summing up 

 the results of these various investigations, that ammonia, derived from 

 amino-acids by the process of deaminization, is converted by union 

 with carbon dioxide into ammonium carbonate, which spontaneously 

 undergoes partial transformation into ammonium carbamate. The 

 latter substance is converted by alternate oxidation and reduction in 

 the liver into urea which is subsequently expelled from the body by the 

 kidneys. In Acidosis, whether induced by disordered metabolism or 

 by the ingestion of acids in excess, this process is impeded and the 

 ammonia is utilized in part to neutralize the excess of acids in the blood 

 and tissues. The output of Ammonia in the urine, therefore, rises in 

 acidosis and is, in fact, a most valuable means of detecting and esti- 

 mating the severity of that condition. 



Next to urea, but as a rule far inferior to it in amount, the most 

 abundant nitrogenous constituent of the urine is Creatinine: 



/NH CO 



HN = C< 



X N(CH 3 ).CH 2 



this substance may be regarded as an anhydride of Creatine, or methyl 

 guanidine acetic acid: 



X NH 2 



HN = c< 



X N(CH 3 ).CH 2 COOH 



which, it will be remembered, is an abundant constituent of muscular 

 tissues. 



The daily output of creatinine in man is from 1.0 to 1.7 grams or 

 from four to six per cent, of the total nitrogenous excretion. Our 

 views regarding the probable origin of creatinine have undergone very 

 important modifications in recent years, thanks to the fundamental 

 investigations of Folin, Van Hoogenhuyze and Verploegh, and Mel- 

 lanby. It was formerly assumed without any doubt that the source 

 of the creatinine in the urine was the creatine in the muscular tissues. 

 This must now be considered to have become uncertain, and in any 

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