NUCLEIC ACIDS 151 



duced an increase of uric acid in the urine, whereupon he formulated the 

 well known leucocytosis theory. 



It is frequently stated that the entire work of Horbaczewski was "un- 

 intelligent" ; yet he showed the physiological origin of uric acid from 

 nucleic acid, and thus solved one of the most important physiological prob- 

 lems of his day. 



The Formation of Uric Acid from the Oxy-purins. Of Horbaczewski's 

 many vagaries, perhaps the most serious was his misconception of the 

 path along which uric acid is formed from nucleic acid. He stated posi- 

 tively, that as no one had been able to oxidize either xanthine or hypo- 

 xanthine to uric acid outside of the body, these substances could not be 

 intermediate products in the passage from nucleic acid to uric acid, and 

 therefore, the purine groups of nucleic acid must have been deaminized and 

 oxidized before they were set free. However this may be, Spitzer (1899) 

 found that an aqueous extract of spleen can bring about the required oxida- 

 tion. To the extract he added a weighed amount of oxy-purine and digested 

 the mixture at 40, as a slow current of air was passed. The oxy-purine 

 disappeared and in its place was found a reasonable equivalent of uric acid. 

 The active agent that brings about the transformation is called xanthine- 

 oxidase. Its presence can be shown in tissue extracts that are devoid of 

 power to bring about other purine transformations ; hence xanthine-oxidase 

 is specific. 



The Formation of Oxy-purines from Amino-purines. In order to pass 

 from nucleic acid to uric acid three transformations are required (though 

 not necessarily in the order given). 



1. Liberation of the purines 



2. Deaminization 



3. Oxidation 



Of these three, deaminization remains to be considered. 



All gland extracts contain nucleic acid ; so that the purine ferments 

 may be studied by examining the purine products of autodigestion. When 

 an aqueous extract of pig's pancreas is allowed to digest at 40, free purine 

 bases soon make their appearance. They are not, however, the amino- 

 purines (guanine and adenine) that one would expect to be formed from 

 nucleic acid, but the two corresponding oxy-purines (xanthine and hypo- 

 xanthine). The .same results are obtained with thymus. These experi- 

 ments lead to the assumption that in the digestion, the amino-purines are 

 first formed but are subsequently converted into the oxy-purines by a deam- 

 i nix ing agent present in the tissue extract. 



A most unexpected result was obtained with pig's spleen. The end 

 products of the self-digestion of an aqueous extract of this tissue are 

 guanine and hypoxanthine, i.e., one amino-purine, and one oxy-purine. It 

 is reasonable to suppose that initially both amino-purines are liberated from 



