698 URINE. 



ether, and then shake the ethereal extracts with dilute soda solution, which dis- 

 solves the oxyacids, while the residue of the phenols which are soluble in ether 

 remains. The alkaline solution of the oxyacids is now faintly acidified with sul- 

 phuric acid, shaken again with ether, the ether removed and allowed to evaporate 

 the residue dissolved in a little water, and the solution tested with MILLON'S 

 reagent. The two oxyacids are best differentiated by their different melting- 

 points. The reader is referred to other works for the method of isolating and 

 separating these two oxyacids. 



Homogentisic Acid (Dioxyphenylacetic Acid), C 8 H 4 O 4 = 



X)H(l) 



C 6 H 3 OH(4) . This acid, which was discovered by MARSHALL 1 and 



\CH 2 COOH(5) 



called by him glycosuric acid, was isolated in larger quantities by WOLKOW 

 and BAUMANN in a case of alcaptonuria and carefully studied by them. 

 They called it homogentisic acid because it is a homologue of gentisic 

 acid, and they showed that the peculiar properties of so-called alcap- 

 tonuric urine in this case were due to this acid. This acid has later 

 been found in many cases of alcaptonuria by EMBDEN, GARNIER and VOIRIN, 

 OGDEN, GARROD, and many others. Glycosuric acid, isolated from 

 alcaptonuric urine by GEYGER, 2 seems to be identical with homogentisic 

 acid. 



The quantity of acid eliminated which varies in most cases between 

 3 and 7 grams per twenty-four hours, and which is higher 14-16 grams 

 in exceptional cases, is increased by food rich in protein. On the 

 ingestion of tyrosine by persons with alcaptonuria, WOLKOW and BAU- 

 MANN and EMBDEN observed a greater quantity of homogentisic acid 

 in the urine. Since LANGSTEIN and E. MEYER showed in a case of alcap- 

 tonuria that the quantity of tyrosine in the protein, even when calculated 

 to a maximum, was not sufficient to account for the quantity of homo- 

 gentisic acid, and that therefore we must admit of another source (the 

 phenylalanine) for the alcapton, FALTA and LANGSTEIN 3 have given a 

 direct proof that homogentisic acid can also be formed from phenylalanine. 

 ABDERHALDEN, BLOCK and RONA 4 have shown that in alcaptonurics the 

 excretion of homogentisic acid is increased by the introduction of 

 tyrosine or phenylalanine in the form of polypeptides, dipeptides as 

 well as tripeptides. The p-tyrosine and phenylalanine are quantitatively 

 converted into homogentisic acid, in alcaptonuria (FALTA). The m- 



1 The Medical News, Philadelphia, January 8, 1887. 



2 Wolkow and Baumann, Zeitschr. f. physiol. Chem., 15; Embden, ibid., 17 and 

 18; Gamier and Voirin, Arch, de Physiol. (5), 4; Ogden, Zeitschr. f. physiol. Chem., 

 20; Geyger, cited from Embden, 1. c., 18. The literature can be found in Fromherz, 

 Ueber Alkaptonurie, Inaug.-Dist. Freiburg, 1908. 



3 Langstein and Meyer, Deutsch. Arch. f. klin. Med., 78; Falta and Langstein, Zeit- 

 schr. f. physiol. Chem., 37; Falta, Der Eiweiss-Stoffwechsel bei der Alkaptonurie, 

 Habilitationsschrift, Naumburg a. S., 1904. 



4 Zeitschr. f. physiol. Chem., 52. 



