: 



HOMOGENTISIC ACID. 699 



and o-tyrosine, on the contrary, are not converted, according to BLUM, 1 

 into homogentisic acid in alcaptonurics and the dibromtyrosine yields 

 just as little homogentisic acid as the bromine or iodine derivatives of 

 protein bodies (FALTA). According to the investigations of LANGSTEIN 

 and MEYER, and especially of FALTA, different proteins yield varying 

 quantities of homogentisic acid in alcaptonuria, and accordingly larger 

 amounts in proportion as the protein is rich in tyrosine and phenylalanine.. 



On this account the quotient H ( = homogentisic acid) : N (nitrogen) 

 is variable on the introduction of different proteins. For example with 

 asein H:N is on an average much higher than with white of egg. In 

 most of the cases of alcaptonuria examined the H:N was equal to 40-50: 

 100, and with the same alcaptonuric, when no essential change in the 

 diet occurs, the quotient is relatively constant. 



WOLKOW and BAUMANN explain the formation of homogentisic acid 

 from tyrosine by an abnormal fermentation in the upper parts of the 

 intestine, but this view has now been generally rejected. The observa- 

 tions of ABDERHALDEN, BLOCK and RoNA 2 that glycyl-Z-tyrosine on 

 subcutaneous injection causes an increased formation of homogentisic 

 acid, disproves this theory ; and indicates a formation of homogentisic 

 acid in the tissues. This acid is also burnt in the healthy organism if not 

 too large quantities of the acid are introduced at one time, and it is the 

 general view that alcaptonuria is an anomaly in the protein metabolism. 



In order to understand this anomaly and the origin of the homogentisic 

 acid we must call attention to the fact that the investigations of O. 

 NEUBAUER and FALTA, LANGSTEIN and others 3 show that only such 

 aromatic acids are converted, in the body, into homogentisic acid, which 

 have a three-membered side-chain which is substituted by NH 2 , OH 

 or H in the a -posit ion to the carboxyl group and not in the /9-posi- 

 tion, p-tyrosine, phenylalanine, phenyl-a-lactic acid and phenyl-pyro- 

 racemic acid are such acids. It can be admitted with FALTA that 

 the phenylalanine in the body by deamidation is converted into 

 phenyl-a-lactic acid, C 6 H 5 .CH 2 .CHOH.COOH, from which by taking 

 up two hydroxyl groups, dioxyphenyl-a -lactic acid (uroleucic acid), 

 (OH) 2 C 6 H 3 .CH 2 .CHOH.COOH, is formed, and then from this by oxida- 

 tion dioxyphenylacetic acid (homogentisic acid), (OH) 2 C 6 H 3 .CH 2 .COOH, 

 is produced. Tyrosine is also supposed to undergo an analogous 

 ransformation whereby a removal of OH groups in the para position 

 must be admitted. 



According to NEUBAUER, 4 on the contrary, the tyrosine, as well as 



1 Arch. f. exp. Path. u. Pharm., 59. 



2 Zeitschr. f. physiol. Chem., 52. 



3 Ibid., 42; see also footnote 3, page 698, and Fromherz, 1. c. 



4 Cited from Centralbl. f. Physiol., 23, 76. 



