511 



The amount of homogentisic acid excreted bears a definite ratio to 

 the total nitrogen output, depending entirely on the diet taken. This 

 Garrod has demonstrated to be the fact by compiling such a table of statis- 

 tics from the experiments of several observers. It appears that a quantity 

 of any given protein will, in an alkaptonuric, tend to form and excrete a 

 definite amount of the alkapton substance, that amount being the maximal 

 one. 



There is reason for belief that the anomaly in function responsible for 

 the failure to break down the alkapton is lodged in the liver, for in normal 

 livers perfusion of homogentisic acid causes it to be 'broken down to 

 acetone (Embden). 



This, however, requires much further experimentation. 



Fromherz and Hermanns believe that the aromatic amino acids nor- 

 mally follow a dual path to destruction and that in alkaptonuria one of 

 the paths is closed. They present the mechanism as follows : 



Hooc 



* H 



CR 



I-CHo 

 I 2 



COOH 



OH 



Homooentisic 



axid 



' 1 



COOH\ 



fone 4* 



ft.ceton 

 -hh^O -hco^ 



COOH 



+H- 



JSTeubauer and Falta emphasized the idea that homogentisic acid is 

 always formed in normal metabolism, but in alkaptonurics it cannot be 

 oxidized as they have lost the power to split the benzol ring. 



