736 URINE. 



alanine in the form of polypeptides, from dipeptides as well as tripeptides. 

 The p-tyrosine and phenylalanine are quantitatively converted into homo- 

 gentisic acid, in alcaptonuria (FALTA). The m- and o-tyrosine, on the 

 contrary, are not converted, according to BLUM/ 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 

 casein 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 BATJMANN 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 ABEEHALDEN, BLOCK and RONA 2 that glycyl-/-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 NEb, OH 

 or O in the a-position to the carboxyl group and not in the /3-position. 

 p-tyrosine, phenylalanine, phenyl-a-lactic acid and phenyl-pyroracemic 

 acid are such acids. It can be admitted with FALTA that the phenyl- 

 alanine 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^CeHs.CH^. 

 CHOH.COOH, is formed, and then from this by oxidation dioxyphenyl- 

 acetic acid (homogentisic acid), (OH^CeHa.CH^.COOH, is produced. 

 Tyrosine is also supposed to undergo an analogous transformation 



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



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



3 Ibid., 42; Fromherz, 1. c. 



