ENZYMES ATTACKING NUCLEIC ACIDS 609 



is strongly inhibited by the antituberculous drug isonicotinic acid hydrazide, 

 that of some other animal DPX hydrolase preparations (enzyme prepara- 

 tions from pigs' brain, human spleen and prostate) is not appreciably in- 

 fluenced by this substance.-^* Zatman ct al. demonstrated that the latter 

 enzyme preparations are capable of catalyzing the exchange of the nico- 

 tinamide group of DPX with isonicotinic acid hydrazide. 



They isolated from incubation mixtures of the enzyme from pigs' brain 

 with DPX and isonicotinic hydrazide a compound which appears to be an 

 analogue of DPX in which the nicotinamide group is replaced by isonico- 

 tinic acid hydrazide. They therefore postulate as a working hypothesis the 

 formation of a complex between the enzyme and the adenosine diphospho- 

 ribosyl group. This complex is believed to contain the free energy of the 

 glycosidic bond. Water and nicotinamide or isonicotinic hydrazide are be- 

 lieved to compete for the reactions with this complex. 



VII. Xanthine Oxidase 



The discovery of xanthine oxidase dates back to Horbaczewski,^^® who 

 observed in 1882 that extracts of various tissues were capable of oxidizing 

 xanthine to uric acid. The early history of the enzymic formation and de- 

 struction of uric acid is connected with the work of many outstanding in- 

 vestigators at the end of the 19th century and cannot be re\'iewed in detail 

 in this article. Much pertinent information can be found in the monograph 

 on uric acid by McCrudden.-'^ It is worth mentioning that as early as 1905, 

 Schittenhelm-^* successfully applied fractionation with ammonium sulfate 

 and dialysis to the partial purification of xanthine oxidase from spleen ex- 

 tracts. His preparation was a mixture of xanthine oxidase and guanase, 

 but was free of uricase activity. The model for Schittenhelm's method 

 was the earlier use of ammonium sulfate for enzyme fractionation by 

 Jacoby,^'^ who developed his procedure in 1899 in Hofmeister's laboratory. 

 Morgan, Stewart, and Hopkins--^ found that milk contained a dehydro- 

 genase which catalyzed the oxidation of hypoxanthine and xanthine to uric 

 acid, and raised the question of its identity with the aldehyde dehydro- 

 genase discovered earlier in milk by Schardinger.^-^ 



2'5 L. T. Zatman, N. O. Kaplan, S. P. Colovvick, and M. M. Ciotti, J. Am. Chem. Soc. 



75, 3293 (1953). 

 "« J. Horbaczevvski, Monatsh. 12, 221 (1882). 

 2'7 F. H. McCrudden, "Uric Acid." Boston, 1905. 

 2'« A. Schittenhelm, Z. physiol. Chem. 43, 228 (1904). 

 215 M. Jacoby, Z. physiol. Chem. 30, 135 (1900). 



220 E. J. Morgan, C. P. Stewart, and F. G. Hopkins, Proc. Roy. Soc. (London) B94, 

 109 (1922-1923). 



221 F. Schardinger, Z. Untersuch. Nahr. u. Gemissm. 5, 22 (1902). 



