ENZYMES ATTACKING NUCLEIC ACIDS 615 



to the conclusion that the oxidation of xanthine and that of uric acid were 

 catalyzed by different enzymes and introduced the name uricase for the 

 enzyme system responsible for the latter process. In 1007, Wiechowski-^" 

 identified allantoin as the main end-product of enzymic uricolysis. This sub- 

 stance had been known much earlier as the main reaction product of oxi- 

 dation of uric acid with permanganate. The first thorough study of the 

 mechanism of uricase action was carried out by Batelh and Stern .-^^ 



Definitioti. Uricase is a uric acid oxidase which^ — under conditions resem- 

 bling those in hving cells — transforms uric acid in yields of more than 95 % 

 to racemic-^- allantoin. Under these conditions, the overall reaction closely 

 approaches the equation given by Keilin and Hartree.-''^ '-" 



CO + CO2 + H2O1 



Presen t Concepts Regarding the Mechanism of Enzymic Uricolysis. A compar- 

 ison of the structures of uric acid and of allantoin shows that enzymic uri- 

 colysis is a complex process involving oxidation and a decarboxylation 

 hivolving the opening of the pyrimidine ring of uric acid. This suggests 

 the assumption that the transformation of uric acid to allantoin is a se- 

 quence of at least two reactions, one oxidative and one decarboxylating 

 step. Since it is most unlikely that these two reactions are catalyzed by 

 the same enzyme, one must either assume, according to Felix et alr'^^ that 

 uricase consists of a mixture of at least two enzymes, or that uric acid is 

 oxidized enzymically to a labile intermediary product which subsequently 

 yields allantoin by a nonenzymic degradation. At present, the latter alterna- 

 tive is favored as a working hypothesis. In the following, some current con- 

 cepts regarding the nature of the labile intermediary compound will be 

 briefly discussed. 



Mechanism of the oxidation reaction. Bentley and Neuberger-^^ demon- 

 strated in experiments with 0^^ and H20^^ that the oxygen of the hydrogen 

 peroxide formed during uricolysis originated exclusively from gaseous oxy- 

 gen. The oxidation of uric acid consists therefore in the transfer of two elec- 

 trons from each uric acid molecule to molecular oxygen. 



240 w. Wiechowski, Bcitr. chem. Path. Physiol. 9, 295 (1907). 



2^' F. Batelli and L. Stern, Biochem. Z. 19, 219 (1909). 



2« L. B. Mendel and H. D. Dakin, J. Biol. Chem. 7, 153 (1916). 



2« D. Keilin and E. F. Hartree, Proc. Roy. Soc. (London) B119, 114 (1936). 



2" C. G. Holmberg, Biochem. J. 33, 1901 (1939). 



2« J. N. Davidson, Biochem. J. 36, 252 (1942). 



2^6 K. Feli.x, F. Scheel, and W. Schuler, Z. ph^jsiol. Chem. 215, 258 (1929). 



2" R. Bentley and A. Neuberger, Biochem. J. 52, 694 (1952). 



