.\IJ\AI'TOMh'/A 579 



the appearaiK'c in tlio urine of liomogentisic acid in a normal individ- 

 ual by feedin<>: large amounts of tyrosine, which is in favor of the 

 view that it is a normal intermediary in tj-rosine catabolism. In any 

 case the administration of tyrosine or phenylalanine, or of tyrosine- 

 rich foods — i. e., proteins — causes a marked increase in the amount 

 of homogentisic acid eliminated in the urine; indeed, this increase is 

 almost quantitative. Normal individuals when jjiven these substances 

 in moderate amounts, or homogentisie acid itself, destroy them com- 

 pletely, so that the latter does not appear at all in the urine.^"'' If 

 alkaptonurics are kept Avithout protein food for some time, the elimi- 

 nation of alkaptonuric acids goes on, although in diminished amounts, 

 indicating that the aromatic amino-acids formed in tissue catabolism 

 also fail to be destroyed and, therefore, appear in the urine as these 

 derivatives. 



Since gentisic acid, 



OH 



COOH, 

 HO 



>\'hen given by mouth, is also eliminated unchanged by alkaptonurics, 

 although completely destroyed by normal individuals, it seems evident 

 that the difficulty in metabolism affects the benzene ring itself and 

 does not depend upon the character of the side-chain. Nonnal organ- 

 isms seem to be capable of destroying such aromatic compounds as 

 pass through a stage of homogentisic acid in being oxidized, which 

 indicates that the benzene ring can be broken up only Avhen oxidized 

 in this particular manner (the 2, 5 position) ; the alkaptonuric differs 

 in being unable to break up even this form (Falta). According to 

 Garrod *' the conversion of tyrosine and phenylalanine into homogen- 

 tisic acid is so complete that the ratio of homogentisic acid to nitro- 

 gen is constant and the same in all cases. Frommherz and Her- 

 manns ^"'^ advance the suggestion that normal oxidation of the aromatic 

 radicals may take place by two routes, one by way of homogentisic 

 acid, the other by way of the 3-4 dioxy-derivatives (i. e., pyrocate- 

 chin), since such derivatives can be readily oxidized in the metabolism 

 of alkaptonurics who cannot destroy homogentesic acid. That is, 

 their deficiency involves onl}^ one of two possible methods of oxidizing 

 aromatic compounds, leaving them considerable capacity for this im- 

 portant metabolic function. The tissues of the alkaptonuric are prob- 

 ably not chemically affected in this condition, for Abderhalden *^ found 

 that the hair and nails of an alkaptonuric contained normal propor- 

 tions of tyrosine. 



46a Gross states that normal scrum destroys liomogentisio acid, which property 

 is lacking in the serum of alkaptonurics ( Biochem. Zeit., 1914 ( (il ) . l(i.i). 



47 Garrod and Clarke, T!iocli«>ni. Zeit., 1!1()7 (2), 217. 

 4"aZeit. physiol. Chem.. 1914 (01), 194. 



48 Zeit. physiol. Chem., 1907 (52), 435. 



