NITROGENOUS WASTE-PRODUCTS 543 



to a certain extent takes the place of urea in the urine of such animals. 

 Confirmatory evidence is supplied by the effects of degenerative 

 changes of the liver upon the urea output. In cirrhosis of the liver 

 and in the liver-degeneration which is induced by Phosphorus -poisoning 

 there is a decided diminution of the urea output, and a concurrent 

 increase in the ammonia output. 



It is impossible to settle this question by extirpation of the liver in 

 mammals, since they do not survive the operation for a sufficient 

 period to permit observation of the excretory products. In birds 

 however, this severe operation may be performed without immediately 

 fatal results. The birds do not, it is true, survive the operation for 

 more than about twenty-four hours, but the time during which they 

 live is sufficient to enable us to ascertain the effect of the removal of 

 the liver upon the excretory products. Unfortunately urea is not 

 the normal end-product of protein catabolism in birds; its place being 

 taken by Uric Acid, which forms from one-half to three-fourths of the 

 total nitrogenous output. However, the uric acid which is excreted by 

 birds is undoubtedly the physiological equivalent of urea. In fact 

 when urea is administered to birds it is excreted in the form of uric 

 acid, so that were the tissues of birds to form urea it would neverthe- 

 less be excreted in this form. The effects of extirpation of the liver in 

 geese were investigated by Minkowski, with the following results: 



Per cent, of total nitrogen in the form of: 

 Uric acid. Ammonia. 



Before extirpation ........ 60 to 70 10 to 18 



After extirpation 3 to 6 45 to 60 



These results are decisive, and the origin of at least ninety per cent, 

 of the uric-acid output in birds must be in the tissues of the liver. 

 Taking all of these different experiments together, therefore, and recol- 

 lecting that the uric-acid excretion of birds is the physiological equiva- 

 lent of the urea output of mammals, we are justified in inferring that 

 the liver is a predominant, if not the sole source of the urea output of 

 mammals. Nevertheless some urea output continues in animals which 

 have an Eck fistula, even when the hepatic artery is also ligated, so 

 that blood is cut off altogether from the liver, and the output of urea 

 is definitely increased under these circumstances by the subcutaneous 

 administration of amino-acids. We can hardly doubt therefore that 

 other tissues besides the liver possess the power of manufacturing 

 urea, although the size and functional activity of the liver enable it 

 to play a predominant role in this, as in other chemical phenomena 

 in which it plays a part. 



The question which next arises is that of the chemical origin or pre- 

 cursor of urea. A direct origin from Arginine is immediately suggested 

 by mere inspection of the structural formula of this amino-acid : 



/NH 2 

 NH = C< 



\NH.CH 2 .CH 2 .CH 2 CH(NH 2 ) COOH 



