700 URINE. 



the other amino-acids, is first transformed into the corresponding keto- 

 acid, p-oxyphenyl pyroracemic acid, OH.C 6 H 4 .CH 2 .CO.COOH, which 

 is then oxidized into the corresponding chinol and transformed into 

 hydroquinone pyroracemic acid, (OH)2C 6 H 3 .CH2.CO.COOH. The homo- 

 gentisic acid is derived from this latter by the splitting off of carbon 

 dioxide by oxidative means. Phenylalanine is either changed into 

 phenyl pyroracemic acid or into p-oxyphenyl pyroracemic acid with 

 tyrosine as intermediary body and then changed as above stated. 



According to the accepted hypothesis the demolition of tyrosine 

 and phenylalanine takes place into homogentisic acid, and the anomaly 

 in the metabolism of alcaptonurics consists in that in these the demoli- 

 tion stops at this point and that the ability to rupture the benzene ring 

 is absent, in the organism, in alcaptonuria. 



The difficulties in accepting the assumption of a transformation of tyrosine 

 into homogentisic acid due to the different positions of the hydroxyi groups in 



the side chain of the two bodies, as shown by the formulae HO<^ ^>OH (homo- 



I 

 CH 2 COOH 



gentisic acid) and <^ , (tyrosine) do not exist now, since we have 



CH 2 ( 



2 CHNH 2 COOH 

 learnt of other analogous processes. For example, the oxidation, by KCMAGAI and 



WoLFFENSTEiN, 1 of paracresol H 3 C<T \3H with potassium persulphate in 



OH 



acid solution. In this manner the expected 3.4 dioxy toluene H 3 C<^ /OH 



was not obtained, but instead homohydroquinone H0<^ /OH, and hence a 



CH 3 

 transference of the alkyl group must have occurred. 



GARROD, 2 who has observed several cases of alcaptonuria, has also 

 tabulated a large number of cases of alcaptonuria which he finds in the 

 literature, and he shows that the anomaly of the protein metabolism 

 occurs oftener in males than in females, and also that blood relationship 

 of the parents (first cousins) predisposes to alcaptonuria. 



On fusing homogentisic acid with alkali it yields gentisic acid (hydro- 

 quinone-carboxylic acid) and hydroquinone. When introduced into the 

 intestine of the dog a part is converted into toluhydroquinone, which 

 is eliminated in the form of an ethereal sulphuric acid. Homogentisic 



1 Ber. d. d. chem. Gesellsch., 41. 



2 Med. chirurg. Transact., 1899 (where all cases up to that time are tabulated); also 

 The Lancet, 1901 and 1902; Garrod and Hele, Journ. of Physiol., 33. 



