ANTIBODY AS A SPECIFIC ENZYME INHIBITOR 171 



The effect was, however, found to be remarkably specific for caffeine, 

 but the pyrimidines uracil, cytosine and thymine showed no inhibitory 

 effect, f^istidine, which contains the imidazole ring, as in the purines, 

 was also found not to have any effect. From the study of the kinetics 

 of the reaction with hypoxanthine they concluded that the inhibitions 

 of the oxidation of hypoxanthine by uric acid and by xanthine are 

 essentially the same in nature. 



Dixon (1926) in a later study determined the specificity of xanthine 

 oxidase. This enzyme, with a high degree of specificity, oxidized only 

 hypoxanthine and xanthine, and adenine to a slight extent, and most 

 aldehydes. It had no action on (a) guanine, alloxan, quinoline, mor- 

 phine, ricin; (b) tryptophane, ketones, benzylamine, peptone; (c) 

 formate, acetate, lactate, succinate, citrate, glutaminate; (d) caffeine, 

 theobromine, uracil, thymine, cytosine, histidine, uric acid; and (e) 

 glycine, tyrosine, alanine, serine, leucine and aspartic acid. 



Coombs (1927) extending the studies on the specificity of xanthine 

 oxidase found that the enzyme had no oxidizing action on 3-, 8-, and 

 9- methylxanthines, 1,3- and 3,8-dimethylxanthines, 1- and 7-meth- 

 ylguanine, 1 ,7-dimethylguanine and benziminazole. Beside hypo- 

 xanthine and xanthine 6,8-dihydroxypurine and 2-thioxanthine were 

 readily oxidizable. The reaction products were uric and thiouric acids, 

 respectively. 



His studies further showed that the introduction of a single methyl 

 group in either ring entirely prevented the oxidation. 



In inhibition experiments hypoxanthine, xanthine, 3-methyl- 

 xanthine, uric acid, adenine 6,8-dihydroxypurine, guanine, 1- and 

 7-methylguanine and 1,7-dimethylguanine were strongly adsorbed on 

 the enzyme; 8- and 9-methylxanthine and alloxan adsorbed only to a 

 small extent. Dimethyl- and trimethylxanthines and pyrimidines ad- 

 sorbed only to a very slight extent. It is evident that the purine ring, 

 and not the pyrimidine nor the imidazole ring, exhibits specific affinity 

 for the enzyme. 



The results of this study showed clearly that the degree of adsorp- 

 tion on, or the specific affinity for the enzyme was not only responsible 

 for the oxidation of the purine bases, but also for the inhibition of the 

 enzyme. The results also show that the simpler the structure of the 

 purine compound, the greater is the degree of affinity exhibited for 

 the enzyme. 



