558 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



but these relationships are reasonable if one assumes that the negatively 

 charged Dicumarol reacts with positively charged enzyme groups, and the 

 positively charged basic quinacrine reacts with enzyme anionic groups. 



We must finally evaluate the reliability of quinacrine as an indicator of 

 flavin participation in enzyme reactions. Certainly the mere inhibition of 

 an enzyme by quinacrine does not imply involvement of a flavin coenzyme. 



100 



80 



60 



40 



n 20 



% 



INH 



Fig. 2-19. Effects of pH on the inhibitions of lactate dehydrogenase 



from Propionibacterium pentosaceum by quinacrine and Dicumarol 



at 0.1 mM. (From Molinari and Lara, 1960.) 



The observations of Hemker and Hiilsman (1960) support the opinion of 

 Hellerman et al. (1946) that quinacrine is a relatively nonspecific inhibitor, 

 due to its affinity for proteins in general. If a reversal of the inhibition by 

 FMN or FAD is demonstrated, there is more likelihood for the participation 

 of a flavin, but even here one must consider the possible complexing of the 

 quinacrine by the reversing flavin. Also it seems that flavin nucleotides 

 which are not coenzymically active are often as good reversors as the co- 

 enzyme itself, indicating some other mechanism than competition for the 

 active center. It would seem to me that quinacrine would be one of the least 

 likely specific antagonists of FMN or FAD, since structurally it is not as 

 close as many other analogs. An ideal indicator for flavins would be phos- 



