506 



Another method of its synthesis is from isatinic acid, as described by 

 Neubauer and Falta : 



COOH 

 AciA 



OH 



COOH 



AcU 



The formation of alkapton in the body was first investigated by Bau- 

 mann and Wolkow. They had surmised that the aromatic fraction of 

 the protein molecule was responsible for the formation of homogentisic 

 acid. Upon feeding an alkaptonuric with 10 grams of tyrosin, they ob- 

 tained a yield of 7.5 grams of alkapton in the urine, that is, over eighty 

 per cent of the theoretically possible quantity. An even larger excretion 

 (93.5 per cent) of homogentisic acid was obtained by Mittelbach after 

 the feeding of tyrosin. 



That it was the protein in the food that was responsible for the alkapton 

 was demonstrated by Ogden and by Stange, who showed that a pure 

 protein diet increased the homogentisic acid from 25 to almost 50 per 

 cent above a mixed diet. 



Not only tyrosin, but a number of other compounds have been shown 

 to cause the formation of homogentisic acid. 



We have enumerated in the accompanying table the alkapton formers, 

 in alkaptonuric subjects, and those substances which do not yield 

 alkapton. 



