THE AROMATIC OXY- ACIDS. 275 



possible exception of the last mentioned, all these substances are 

 identical with homogentisinic acid. This was first isolated from an 

 " alkapton " urine by Baumann and Wolkow, and has since been 

 found in every case that has been examined in this direction. 



Alkaptonuria, though it may occur in disease, has been regarded as 

 the expression of an unusual form of intestinal putrefaction which 

 in no way affects the health of the individual. Some observers, on 

 the other hand, look upon it as a metabolic abnormality, and it must 

 be confessed that micro-organisms have thus far not been isolated 

 from the intestinal contents of such cases which are capable of 

 effecting the transformation of tyrosin to homogentisinic acid in 

 vitro. That tyrosin can be its source is undoubted, for it has been 

 shown that following the administration of this substance homo- 

 gentisinic acid appears in the urine in greatly increased amount. 

 Baumann thus noted that while the average elimination in one of 

 his cases amounted to 4.6 grammes, 14 grammes were once extracted 

 in the twenty-four hours after tyrosin had been ingested. It is to 

 be noted, however, that tyrosin is a member of the para-series, while 

 homogentisinic acid belongs to the ortho-series : 



C.OH CH 



HC CH HO.C CH 



HC CH HC C.QH 



C.CH,.CH(NH 2 )COOH C.CH 2 .COOH 



Tyrosin. Homogentisinic acid. 



A direct transformation of the one into the other can accordingly not 

 occur. But we may imagine that the hydroxyl group of the tyrosin 

 is first removed by reduction, and that the benzol radicle is then 

 oxidized again in two para-positions. 



Phenyl-alanin, like tyrosin, will also increase the elimination of 

 homogentisinic acid (in one case 89.32 per cent, of the ingested 

 phenyl-alanin reappeared as homogentisinic acid). 



The opinion has been expressed of late that homogentisinic acid 

 mav be a normal intermediary product in the destruction of tyrosin 

 and phenyl-alanin and that its formation represents an oxidation 

 which precedes the breaking up of the benzene ring. Its appear- 

 ance in the urine, according to this idea, would be the expression 

 of a metabolic insufficiency which renders the destruction of the 

 benzene ring impossible. As a matter of fact, there are certain 

 observations which render this view quite probable. It is thus 

 known that homogentisinic acid is formed in the rootlets of certain 

 plants from tyrosin, but is normally rapidly destroyed. It appears 

 that both tyrosin and phenyl-alanin are first desamidized, j?-oxy- 

 phenyl-propionic and p-oxy-phenyl-acetic acid resulting, from which 

 homogentisinic acid is formed through oxidation with coincident 

 reduction or transposition of the para-oxy group. 



Isolation. Homogentisinic acid may be conveniently isolated 



