FORMATION OF URIC ACID 413 



The steps by which absorbed proteids are changed to ammonium car- 

 bamate, etc., are as yet undecided. According to one view, while still in the cir- 

 culating medium, they are metabolized by direct contact with the living bio- 

 plasm of the tissues; according to another, they must first be incorporated 

 into the substance of the body tissues and then changed. The intermediate 

 steps occur chiefly in the intestinal tract and in muscle tissue, and there is 

 good reason to suppose that some of the steps are represented by various 

 extractives which are formed in these regions. 'These substances probably 

 break down into carbon dioxide, ammonia, and amido-acids, and are then 

 built up by synthetic processes into ammonium carbamate. Another possible 

 antecedent is ammonium lactate; this is derived from the lactic acid which 

 is produced in large quantities in the muscles. The elimination of urea is 

 increased very slightly by muscular activity. But there is no direct relation- 

 ship between the amount of work done and the amount of nitrogen excreted 

 as urea. 



There is experimental evidence to show that while the liver produces the 

 major part of the urea eliminated, other organs or tissues are capable of 

 forming it to a limited degree. 



Formation of Uric Acid. The relations which uric acid and urea bear 

 to each other in different animals, as we have seen, is still obscure. The 

 fact that they exist together in the same urine makes it seem probable that 

 they have different origins. The entire replacement of one by the other, as 

 of urea by uric acid in the urine of birds, serpents, and many insects, and of 

 uric acid by urea, in the urine of the feline tribe of mammals, shows their 

 close relationship. But although it is true that one molecule of uric acid 

 is capable of splitting up into two molecules of urea and one of mes-oxalic 

 acid, this is not evidence that uric acid is an antecedent of urea in the 

 nitrogenous metabolism of the body. The chemical structure of the uric 

 acid shows it has a nucleus of purin, and therefore is a close relative of 

 adenin, guanin, hypoxanthin, xanthin, theobromin, caffein, etc. The nucleins 

 on cleavage yield members of this group, hence may be looked to as the 

 primary source of uric acid in man. Uric acid, according to Chittenden, 

 has a double origin endogenous from nuclear metabolism, and exogenous 

 from metabolism of foods rich in nuclear and other purin compounds. In 

 man, at least, the uric acid is to be ascribed to these two sources. 



Operative experiments on birds tend to show that the final step in uric- 

 acid formation takes place chiefly in the liver, for on the removal of this organ 

 other nitrogenous compounds, i.e., lactates, accumulate in the blood. 



Hippuric Acid, Creatinin, etc. The hippuric acid found in the 

 urine is derived in part from some constituents of vegetable diet, though man 

 has no hippuric acid, as such, in his food, nor, commonly, any benzoic acid that 

 might be converted into it. It is derived in part from the natural disintegra- 

 tion of tissues, independent of vegetable food. Weismann constantly found 



