512 10. EFFECTS OF MORE THAN ONE INHIBITOR 



is nearly expressed by summation. This was explained in part by the for- 

 mation of a complex between sulfanilamide and urethane. The urethane 

 was in much higher concentration than the sulfanilamide and at low tem- 

 peratures the sulfanilamide was to a large extent complexed and inactive; 

 increase in temi^erature resulted in a greater dissociation of the complex. 

 This explanation is not entirely satisfactory. In the first place, in Vibrio 

 the combined inhibition followed the inhibition by urethane alone quite 

 closely, at every temperature sulfanilamide contributing little to the in- 

 hibition; from this it would appear that temperature had very little effect 

 on the ability of sulfanilamide to inhibit in the presence of urethane. In 

 the second place, the results in Photobacterium are not indicative of com- 

 plex formation at low temperatures (even though only half the concentra- 

 tion of urethane used with Vibrio was present), since the combined inhibi- 

 tion was closer to that with sulfanilamide alone. If complex formation were 

 the sole origin of the phenomenon, one would expect both organisms to 

 behave similarly. Part of the antagonism of sulfanilamide may be due to 

 complex formation but in addition there would appear to be a metabolic 

 interaction, the nature of which must remain unknown until the i)athways 

 and sites of inhibition are better understood. It is likely that sulfanilamide 

 and urethane act on different pathways or sites because of the opposite 

 temperature dependence of their inhibitions. 



A reduction in metabolic rate might be expected to induce frequently 

 some resistance to an inhibitor. This will be discussed in more detail in 

 Chapter 15 but it is interesting in connection with the inhibition of lumi- 

 nescence to realize that the slower operation of a metabolic pathway can 

 alter the dependence of the rate on enzyme or coenzyme concentrations. 

 During slow activity, the enzymes or coenzymes have greater opportunity 

 to be in excess of what is needed, and thus inhibition or inactivation will 

 not so readily cause a reduction in the rate. Such a factor might be involved 

 in the antagonism between sulfanilamide and urethane. 



