870 PHYSIOLOGY 



entirely replace protein in the food. So far we are acquainted with 

 three compounds of the aromatic series among the products of dis- 

 integration of the protein molecule. These are tyrosine, phenylalanine, 

 and tryptophane. Since these substances are also contained in the 

 protein constituents of the tissues we may assume that, after they 

 have been set free by the digestive hydrolysis of proteins, they are 

 absorbed and built up again with the other ammo-acids in appropriate 

 groupings. Like these they are susceptible of complete oxidation in 

 the body, so that they can contribute to the supply of energy. Any 

 one of these substances, administered with the food or subcutaneously, 

 is entirely destroyed, with the production of urea, carbon dioxide, 

 and water. In this respect they present a marked contrast to almost 

 all other compounds of the aromatic series. In these we find that the 

 benzene ring is extremely stable, so that, although changes may occur 

 in its side-chains, the benzene ring itself appears intact in the urine, 

 and is not broken up in the body. Thus benzoic acid, benzylalcohol, 

 and phenyl propionic acid, when administered, are passed in the 

 urine as hippuric acid (benzoyl glycine). Indol and skatol, which 

 are closely allied to tryptophane, undergo oxidation in the body 

 without further modification and appear in the urine as conjugated 

 aromatic sulphates. 



Some light is thrown on the conditions of breakdown of these 

 aromatic bodies by the study of a rare disorder in metabolism, which 

 may occur in certain families and is known as alcaptonuria. In this 

 condition, which is congenital and lasts throughout life, the urine 

 darkens considerably when made alkaline and exposed to the air. It 

 has the power of reducing Fehling's solution, so that the presence of 

 sugar might be suspected. On analysis the peculiarities of the urine 

 are found to be due to the presence in it of a substance known as 

 homogentisic acid. This is dioxyphenyl acetic acid. 



HO A 



U H 



CH 2 COOH 



The amount of this substance in the urine bears a constant ratio to 

 the nitrogen excreted. It does not disappear during starvation, and 

 is much increased on a large protein diet. It must therefore be 

 derived from the disintegration of proteins both exogenous and 

 endogenous. If tyrosine or phenylalanine be administered to patients 

 affected with this disorder, both substances are quantitatively con- 

 verted into homogentisic acid. The ratio of this acid to the total 

 nitrogen indicates that the whole of the tyrosine and phenylalanine 

 of the protein molecule, whether set free in the alimentary canal or 



