578 GASTR0-INTE8TIKAL "AUTOIXrOXICATIOy" 



of these aromatic bodies to the aromatic constituents of the proteins 

 is best shown by comparing their structural formula3 : 



rhenylalanine, /^ \ CIL — CHXH, — COOH. 



Tyrosine, HO—/ > CIL — CHXH„ — COOH. 



OH 

 Uroleucic aci(i,->4 / \ CH„ — CHOH — COOH. 



HO 



OH 

 Homogcntisic acid, /^ \ CK, — COOH. 



HO 

 Apparently the condition depends upon an abnormality in the in- 

 termediary metabolism, and not upon an abnormal formatiou of homo- 

 urentisie acid through intestinal putrefaction, as was at first believed. 

 Alkaptonuria is never observed in slight degrees; if there is any 

 homogcntisic acid in the urine at all it is there in large amounts (4-5 

 grams per day), depending on the diet, for when the error in metabo- 

 lism is present at all it is complete. On a mixed diet the ratio of 

 homogcntisic acid to nitrogen in the uriue is 40^5 to 100. The pre- 

 vailing idea has been that the abnormality consists not in the excessive 

 formation of homogcntisic acid, but in a lack of ability on the part 

 of the alkaptonurie individual to split open the benzene ring. It is 

 generally stated that tyrosine and phenylalanine first suffer a split- 

 ting out of the nitrogen radical from the alanine side-chain, and then 

 are oxidized into homogcntisic acid, following which changes comes a 

 disintegration of the benzene ring, with subsequent complete oxida- 

 tion. On this basis the alkaptouuric accomplishes the conversion into 

 the ox3^-acid, but the process stops there. Wakeman and Dakin,*^ 

 hoAvever, have obtained evidence that in the normal oxidation of tyro- 

 sine and phenylalanine, homogcntisic acid is not an intermediary 

 product, and Dakin statop that the alkaptonurie can destroy simple 

 derivatives of plienylalanine and tyrosine, provided their structure 

 is such that the formation of substances of tlu^ type of homogentisic 

 acid is precluded. He believes that in alkaptonuria there is abnoi'mal 

 formation of homogentisic acid as well as a failure to destroy it when 

 formed. On the other hand, Abderhalden '**' has been able to cause 



dence of syphilis, and in one case this reaction disappeared wlien the ]>atient 

 was given large amounts of tyrosine (Siiderliergh, Nord. Med. Arkiv., IHI.") (48), 



1). ; 



4» The older writers stated that uroleucic acid commonly accompanied homo- 

 gentisic acid in the urine of alkaptonuria, hut later observations do not confirm 

 this. (Oswald, Zeit. phvsiol. Chem.. 1914 (0.3), n07 ) . 



■•5 .Tour. Biol. Cliem., 1011 (f)), 130 and 151. 



<«Zeit. physiol. Chem., 1012 (77), 454. 



