WASTE-PRODUCTS OF THE SULPHUR METABOLISM 559 



reduction of cupric hydroxide solution by the urine of an alcaptonuric 

 individual is, however, accompanied by darkening or even blackening 

 of the fluid, so that no confusion of diagnosis should be possible even 

 on superficial observation. 



The homogentisic acid in alcaptonuria arises from the tyrosine and 

 phenylalanine radicals in the proteins of the food. If the diet contains 

 little tyrosine or phenylalanine the output sinks, if much it rises. 

 The administration of tyrosine or phenylalanine by mouth, or of 

 glycyltyrosine hypodermically, leads to quantitative excretion of the 

 aromatic nucleus in the form of homogentisic acid. The elimination 

 continues, although it is reduced, in starvation, and this, together 

 with the fact that it may be enhanced by subcutaneous or intravenous 

 administration of the parent acids, shows that the homogentisic acid 

 is not derived from intestinal cleavage or putrefaction. 



Evidently the alcaptonuric is unable to complete the oxidation of 

 the aromatic nuclei of Tyrosine and Phenylalanine, just as the Diabetic 

 is unable to complete the oxidation of /3-oxybutyric acid. Curiously 

 enough, however, as Garrod and Neubauer have shown, tryptophane 

 is normally utilized by persons who display alcaptonuria. 



According to Garrod there is but one degree of alcaptonuria and that 

 is complete. Either the excretion of homogentisic acid amounts to 

 several grams a day or it is absent from the urine, and usually the 

 condition is present from earliest childhood. It is evidently the exog- 

 enous metabolism only of tyrosine and phenylalanine which is affected 

 for no defect of development or loss of weight in the adult occurs 

 such as we would expect to happen, were tissue-protein destroyed to 

 produce the homogentisic acid. It is the circulating amino-acids, which 

 normally undergo complete combustion after deaminization, which are 

 the source of this substance. 



It is probable that homogentisic acid represents a normal inter- 

 mediate product in the oxidation of the oxyphenyl-oxypropionic acid 

 which results from the deaminization of tyrosine. The curious fea- 

 ture of the transformation, however, resides in the fact that whereas 

 tyrosine has only one hydroxyl-group in the benzene nucleus and that 

 in the para position, homogentisic acid has two, one in the ortho and 

 the other in the meta position. It is found, however, that this is the 

 only class of dioxyphenols which is oxidized by normal persons, other 

 dioxyphenols being excreted in the form of conjugates in the urine. 

 The alcaptonuric therefore differs from the normal person in that his 

 inability to oxidize diphenols extends to the single class which normal 

 individuals can oxidize, namely those in which the hydroxyl-groups 

 occupy the ortho and meta positions relatively to the side-group. 



WASTE-PRODUCTS OF THE SULPHUR METABOLISM. 



The waste-products of the sulphur metabolism are of three types, 

 namely Inorganic Sulphates, Ethereal or Conjugated Sulphates and the 



