viz KATABOLIC CONSTITUENTS OF UEINE 393 



urine of fasting, and that of dogs fed on meat that has been 

 exhausted, and entirely or almost entirely deprived of its creatine 

 (Eubner). Another fact which shows that creatinine is specially 

 formed by the muscles, is that muscular work and fatigue increase 

 the quantity of creatinine in the urine (Grocco, Moitessier, 

 Ackermann). 



V. The urine of man and other mammals constantly contains a 

 group of aromatic compounds, among which hippuric acid largely 

 predominates. This results from the combination of lenzoic acid 

 with glycocoll with loss of one molecule of water : 



( Y.KftCOOH + CH 2 (NH,).COOH = C 6 H-CO - NH.CH 2 -COOH + H a O 



Benzole acid. Ulycoeoll. Hippuric acid. 



Hippuric acid (in combination with alkalies), although it is 

 present only in small quantities in human urine, is never absent 

 even during an exclusively flesh diet and in fasting. It arises 

 from the aromatic substances of the food, which are converted as 

 the result of bacterial fermentation in the intestinal canal into 

 benzoic acid : this, after absorption, combines with the glycocoll, 

 with formation of hippuric acid, by loss of water. These aromatic 

 substances come from hydrolytic cleavage of the proteins, which, 

 as we know, contain an aromatic nucleus. Glycocoll is another 

 cleavage product of the same substances, formed by katabolic 

 processes in the tissues. 



With an ordinary mixed diet the hippuric acid content of the 

 urine fluctuates from O'l to I/O grin, per diem, the usual average 

 being 0'7 grrn. per diem. But it is much increased by a 

 vegetable diet, especially after a large consumption of fruit and 

 vegetables. Hippuric acid is plentiful in the urine of herbivora, 

 and to a large extent replaces uric acid, which is present only in 

 a small amount. These facts show clearly that the chief part of 

 the hippuric acid of the urine is of alimentary origin, because 

 the food-stuffs contain either benzoic acid itself or substances 

 which are capable of conversion, in the intestinal tube or within 

 the tissues, into this acid. 



In 1824 Wohler discovered that it is only necessary to mix 

 benzoic acid with the food of any mammal in order to see it 

 reappear in the urine in the form of hippuric acid. This discovery, 

 which was confirmed by subsequent observers, was the first well- 

 established instance of synthesis within the animal body. In 1876 

 Schmiedeberg and Bunge made an exhaustive study of the 

 question in which organ the synthesis that gave rise to hippuric 

 acid took place. They excluded the possibility of its being the 

 liver, because in dehepatised frogs the subcutaneous injection of 

 benzoic acid, or benzoic acid and glycocoll, gave rise to the forma- 

 tion of hippuric acid. They found that in dogs the organs which 



