682 THE SEAT OF FORMATION OF UREA 



urea. We have also seen that there is some evidence that the 

 liver and other tissues can convert the N of these acids into 

 ammonia, and presumably by the action of a ferment. But con- 

 clusive experimental evidence that the liver is the organ which 

 converts the mono-amino acids into urea is still wanting. Lowi 

 showed that glycin digested with a liver extract is converted into 

 an amide, but he did not determine its nature. Salaskin carried 

 out experiments in which he circulated through a surviving dog's 

 liver blood to which glycin, leucin, or aspartic acid had been added. 

 In each case he found increased urea values in the blood. Unfor- 

 tunately his estimations were done by Schondorffs method, and, 

 however likely, it is not absolutely certain that urea and not 

 some other amide was actually produced. 



The same is true in the case of uric acid. We have seen 

 that it is partly destroyed and largely converted into urea in 

 the body. We have seen that the liver and other organs possess 

 a ferment which can break up uric acid, but we have no con- 

 clusive evidence that the liver actually does manufacture urea 

 out of uric acid. Hahn, Massen, Nencki, and Pawlow observed 

 in dogs, with ligature of the hepatic artery in addition to an 

 Eck's fistula, the usual changes in the urinary ammonia and 

 urea, but in addition an increased excretion of uric acid both 

 actual and relative to the urea. This increase they ascribed 

 to a greater destruction of nucleo-proteid in the tissues. But it 

 might equally well be due to the failure of the liver to convert 

 uric acid into urea. Ascoli carried out a series of experiments in 

 which he circulated through a dog's liver blood containing known 

 quantities of uric acid. He found that within an hour a loss 

 of uric acid took place which was in excess of the loss due to 

 the action of the blood on the uric acid. He further showed 

 by SchondorfTs method increased urea values in the perfused 

 blood. 



Is Urea formed in Tissues other than the Liver ? The fact that 

 many organs yield arginin on hydrolysis and also possess arginase 

 suggests that the answer to the question must be in the affirma- 

 tive, so far as this origin of urea is concerned. But, as has been 

 pointed out already, we have no knowledge of the relative magni- 

 tudes of this and of other methods of urea production, and we 

 have still to discuss the question whether or not tissues other than 

 the liver can form urea from ammonia or some other substance. 



