METABOLISM OF PROTEINS 571 



such in the urine, but coupled with glycocoll as hippuric acid. 

 Thus 



CjHg.COOH 4- CH 2 (NH 2 ) .COOH - H 2 O =C,H 5 .CO.NH.CH 8 .COOH 



Benzoic acid. Glycocoll. Hippuric acid. 



Benzoic acid, therefore, meets glycin in the body, and combines 

 with it, as fatty acids meet glycerin and combine with it. Even 

 starving animals fed with benzoic acid excrete large quantities of 

 hippuric acid. Yet their tissues, as shown by analysis after death, 

 yield as much glycocoll as starving animals which have received no 

 benzoic acid, and excreted little or no hippuric acid. Many other 

 acids which are totally foreign to the body are, when ingested, 

 paired in the same way with glycocoll and excreted in the urine. 

 Even substances whose chemical nature does not permit of a direct 

 union with the glycin are often altered by oxidation or reduction 

 till they can unite with it, and then the coupling takes place, and 

 the conjugated acid is eliminated by the kidneys. The paired or 

 aromatic sulphuric acid which we have already recognized as a 

 normal constituent of the urine affords another instance of this 

 coupling. Cystein among the derivatives of proteins, and glycu- 

 ronic acid (p. 476) among the derivatives of carbo-hydrates, can 

 also unite in the same way with numerous compounds. There is 

 some evidence that the physiological significance of this process is 

 that the toxicity of the foreign substances, or, as in the case of the 

 aromatic sulphuric acid of the urine, of substances formed by 

 bacteria in the intestine, or even produced in the metabolism of the 

 tissues, is diminished by the pairing. 



The place and manner of formation of hippuric acid have been 

 investigated with the following result : If an excised kidney is per- 

 fused with blood containing benzoic acid, or, better, benzoic acid 

 and glycin, hippuric acid is formed. Oxygen is required, for if the 

 blood is saturated with carbon monoxide, or if serum is employed 

 for perfusion, the synthesis does not take place. The kidney cells 

 must be intact, for if a mixture of blood, glycin, and benzoic acid 

 be added to a minced kidney immediately after its removal from 

 the body, hippuric acid is produced, but not if the kidney has been 

 crushed in a mortar. Nevertheless, there is some evidence that a 

 ferment is concerned, and the known mechanism of similar reactions 

 in the body scarcely permits the physiologist to acquiesce in any 

 other explanation. It must not be forgotten that the urinary 

 constituents which must come into contact with the ferment when 

 the kidney is crushed may injure or inhibit the enzyme. In 

 herbivora hippuric acid cannot normally be detected in the blood; 

 it is present in large quantities in the urine; it must therefore be 

 manufactured in the kidney, not merely separated by it. In certain 

 animals, as the dog, the kidney is the sole seat of the production 



