280 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



xanthine to uric acid, each step essentially involving the addition of water 

 and the removal of two hydrogen atoms which are transferred to oxygen 

 along a typical electron transport sequence. Hydroxypurines exhibit keto- 

 enol tautomerism, and it is only recently that spectroscopic evidence point- 

 ing to the predominance of the keto form has been obtained (Mason, 

 1957). The structures of the purines and pteridines to be discussed will 

 be written as far as possible in conformity to these results. However, in 

 some cases it is difficult to assign the most important structure, especially 

 in multiply substituted compounds. Ionization may also be a complicating 

 factor. Most purines appear to be predominantly neutral at physiological 

 pH (piiC^ between 1 and 4; pK^, between 8 and 12), but some, such as uric 

 acid, lose a proton in the acid pH range and physiologically exist as anions 

 (e.g., pK^ for uric acid is 5.4). The site of loss of the proton is not known 

 and it is quite possible that the anions should be considered as being 

 equilibrium mixtures of several structures. The form in which they are 

 written, hence, does not imply that this structure is the only one present, 

 or even that it is necessarily the most important structure. Such considera- 

 tions become important in treating the forces between these compounds 

 and the enzyme. A final factor must be borne in mind: the most stable 

 form in solution is possibly not the form in which the purine is bound to 

 the enzyme surface, inasmuch as the interaction may modify the structure 

 appreciably. 



Purine Analogs 



Dixon and Tliurlow (1924) reported that xanthine oxidase is inhibited 

 by various purines, such as adenine and uric acid, but no quantitative data 

 were given. There was no further investigation until the introduction of 

 the azapurines. 2-Azaadenine and 2-azahypoxanthine, like many purine 



Purine 



Guanine 



8-Azaguanine 



NH. 



NH, 



NH. 



Pyrazoloisoguanine 



