272 LECTURE XII. 



acid was administered to a man afflicted with alcaptonuria, the elimination 

 of the homogentisic acid increased in the same manner as when tyrosine 

 was used. Both of these elementary aromatic constituents of albumin 

 are, therefore, to be considered as forming the basis for the formation of 

 the alcapton acids. 1 It is very important to note that as far as our present 

 knowledge is concerned, all the phenyl-alanine and tyrosine in the food 

 materials are converted by persons afflicted with alcaptonuria, into the 

 alcapton acids, so that the disturbance in the disintegration of these amino 

 acids seems to be very complete. 



A comparison of the constitution of tyrosine and of phenyl-alanine with 

 that of the alcapton acids shows us that the formation of the latter from 

 the former is not an altogether simple process. 



A A OH 



CH 2 . CH . NH 2 . COOH CH 2 . CH . NH 2 .COOH 



phenyl-alanine Tyrosine 



HO /, HO ^ 



OH VOH 



CH 2 . CH(OH) . COOH CH 2 . COOH 



Uroleucic acid Homogentisic acid 



Tyrosine is para-hydroxyphenyl-a-aminopropionic acid, and phenyl- 

 alanine is a phenyl-a-aminopropionic acid. All the decomposition products 

 of tyrosine which we have met with, partly as putrefactive products, and 

 partly as products arising from intermediate metabolism, belong, as 

 tyrosine itself does, to the para compounds. The constitutional formulae 

 of homogentisic and uroleucic acids, as shown above, indicate that this 

 is not true of them. It is difficult to understand the formation of both 

 of these alcapton acids from any of the known aromatic components of the 

 proteins. In the transformation of tyrosine into homogentisic acid, the 

 hydroxyl group must certainly be eliminated, either by being split off 

 or by migrating. Two other places in the benzene ring are then oxidized, 

 hydroxyl groups being formed para to one another. Altering the side- 

 chain of the amino-propionic acid into an acetic acid residue presents 

 nothing unusual, and can easily arise by merely removing the amino group. 



It is very probable that the homogentisic acid is not directly produced 

 from tyrosin, but from its derivative, p-hydroxyphenylacetic acid. It is 

 here evidently that the anomaly in the further degradation of tyrosine 

 occurs. The corresponding compound from phenyl-alanine is phenylacetic 



1 Cf. also A. C. Garrod and T. S. Hele: J. Physiol. 33, 198 (1905). 



