ALKAPTONURIA 475 



the benzene ring. Tyrosin and phenylalanin seem normally 

 to first suffer a splitting out of the nitrogen radical from the 

 alanin side-chain, and then to be oxidized into uroleucic and 

 homogentisic acids, following which changes comes a disintegra- 

 tion of the benzene ring, with subsequent complete oxidation. 

 The alkaptonuric accomplishes the conversion into the oxy-acid, 

 but the process stops there. Consequently the administration 

 of tyrosin or phenylalanin, or of tyrosin-rich foods i. e., 

 proteids causes a marked increase in the amount of homo- 

 gentisic acid eliminated in the urine (uroleucic acid, which is the 

 precursor of homogentisic acid, has been observed abundantly in 

 but one case) ; indeed, this increase is almost quantitative. 

 Normal individuals when given these substances, or homogen- 

 tisic acid itself, destroy them completely, so that the latter does 

 not appear at all in the urine. If alkaptonurics are kept without 

 proteid food for some time, the elimination of alkaptonuric acids 

 goes on, although in diminished amounts, indicating that the 

 aromatic amino-acids formed in tissue katabolism also fail to be 

 destroyed and, therefore, appear in the urine as these derivatives. 

 As gentisic acid, 



OH 

 ; COOH, 



HO 



when given by mouth, is also eliminated unchanged by alkap- 

 tonurics, although completely destroyed by normal individuals, 

 it seem evident that the difficulty in metabolism affects the ben- 

 zene ring itself, and does not depend upon the character of the 

 side-chain. Normal organisms seem to be capable of destroying 

 only such aromatic compounds as pass through a stage of homo- 

 gentisic acid in being oxidized, which indicates that the benzene 

 ring can be broken up only when oxidized in this particular 

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

 unable to break up even this form (Falta). 



In some cases of alkaptonuria a pigmentation of the carti- 

 lages also occurs, ochronosis, but the association is not constant ; 

 ochronosis may occur without alkaptonuria, and conversely. 

 (See "Ochronosis/' page 397.) 



(2) SUBSTANCES ARISING FROM THE FATTY ACID RADICALS 

 (AMINO-ACIDS) OF PROTEIDS 



As stated in the introductory chapter, the proteid molecule 

 consists of a combination of a great number of organic acids, 

 of various sorts, all of which have as a common characteristic 



