778 



PHYSIOLOGY 



intestinal wall, or after absorption into other tissues of the body, the nucleic 

 acid is subjected to hydrolytic changes by the agency of ferments which 

 may be classed as nucleases. These are, however, of different kinds, the 

 phosphonuclease splitting off the phosphoric acid and leaving the nucleo- 

 sides, while the purine nucleases, which are more effective in a slightly 

 alkaline medium, split off the purines, leaving the phosphoric acid com- 

 bined with the carbohydrate. The purines set free in this way undergo 

 further changes. The hypoxanthin derived from inosinic acid is converted 

 under the action of an oxidase first into xanthine and then into uric acid. 



This was one of the earliest facts discovered in the metabolism of puiines. 

 Horbaczewski showed that if spleen pulp be digested with blood for some time, it is 

 possible to extract a considerable amount of xanthine from the mixture. If, however, 

 oxygen be bubbled through the fluid, the xanthine disappears, its place being taken 

 by uric acid. 



From the more complex nucleic acids the amino-purines, adenine, and 

 guanine, are set free. These first undergo deamination under the action 

 of special ferments, adenase and guanase, and are thus converted into 

 hypoxanthine and xanthine respectively. These bodies then, under the 

 action of oxidases, may be converted into uric acid. 



All these changes occur in the living body, though not necessarily in the order just 

 set out. Thus when the pyrimidine derivatives are administered to dogs, they pass 

 out unchanged. If, however, free nucleic acid be administered to the animal, no trace 

 of these derivatives can be found in the urine, so that they must have undergone com- 

 plete oxidation. In the same way the dog's liver is able to deaminise completely 

 the adenine group of nucleic acid, converting it into hypoxanthine, but is without 

 effect on free adenine. It is evident, therefore, that the various ferments which have 

 baen described act partly on the whole nucleoside molecule, partly on the products 

 of its decomposition, and that the results of the action of the body ferments are not 

 the same in the two cases. 



If we make this reservation, namely, that the constituent parts of the nucleic acid 

 molecule may undergo changes while still bound to the other parts, we may represent 

 diagrammatically the formation of uric acid from nucleic acid as follows : 



Ferments 

 Nuclease 



deaminase 

 hydrolysis 

 oxidase 

 oxidase 



oxidase 

 (uricase) 



Nucleic acid 



I I II- ~l 



Phosphoric acid guanosine adenosine uridine cytidine 



xanthosine 



inosme 



fate unknown 



xanthine hypoxanthine 



xanthine 



I 



uric acid 

 allantoin. (in doors) 



