508 ROSENBLOOM AND KAHN 



tyrosin of the food protein is changed by the intestinal bacteria into homo- 

 gentisic acid. This explanation, however, met with severe criticism, and 

 Baumann's pupil, Embden, was the first to cast aspersion on its validity. 

 The objection to the intestinal bacterial origin of alkapton may be sum- 

 marized as follows : 



1. It is impossible to influence the excretion of alkapton by means 

 of intestinal disinfectants. (Embden.) 



2. No organism can be grown from the feces that is capable of trans- 

 forming tyrosin into the homogentisic acid. (Embden.) 



3. Fasting an alkaptonuric individual shows that the alkapton is 

 derived not only from the food protein, but also from the catabolism of 

 the tissue protein. This was first demonstrated by Mittelbach. He found 

 that on a full diet an alkaptonuric excreted 4.66 grams alkapton, whereas 

 during starvation he still excreted 2.57 grams of this substance. 



4. Abstinence from protein food, while it diminishes, does not arrest 

 the elimination of the homogentisic acid in an alkaptonuric. (Langstein 

 and Meyer.) 



5. It was demonstrated by Abderhalden, Bloch and Rona that the 

 parenteral administration of glycyl-1 tyrosin caused an increase in the 

 alkapton excretion, in which case surely the intestinal flora could have 

 had no effect. 



6. Feeding proteins poor in tyrosin did not influence the alkapton 

 excretion in the urine, showing that the tyrosin in the alimentary canal 

 \vas not the only aromatic compound that is changed to homogentisic acid, 

 (Falta.) 



7. Should the intestine thus change the tyrosin and the phenyl alanin 

 before absorption, the tissue protein of alkaptonurics should exhibit a 

 deficiency of these aromatic amino acids, seeing that they are not synthe- 

 sized in the animal organism. Abderhalden and Falta, who have analyzed 

 the blood proteins as well as the proteins of the hair and nails of alkapto- 

 nuric subjects, have not found any deviation from the normal. 



How then is the homogentisic acid formed ? If one will glance at 

 the list of alkapton formers enumerated previously, one will see that they 

 have all of the following properties in common (Neuberg) : 



1. They are aromatic acids. 



2. They have a three membered side chain. 



3. The side chain can undergo substitution in the a-position. 



4. The substitution products may be ct-amino, -oxy, or cc-keto 

 aoids. 



5. The benzol ring must either be unaltered, or 



6. The benzol ring may undergo substitution in the para position 

 alone or in the 2-5 position simultaneously. 



It was. found by Blum that orthotyrosin and metaty rosin did not 

 influence the excretion of alkapton. Not only is this the case for the 



