494 



10. EFFECTS OF MOKE THAN ONE INHIBITOR 



was occasionally complete. Curves showing the inhibitions produced by 

 different concentrations of diisopropylfluorophosphate in the presence of 

 butyrylcholine are given in Fig. 10-2. The lower the concentration of di- 

 isopropylfluorophosphate, the greater the protection, as would be expected. 



LOG (DFPJ 



Fig. 10-2. Inhibition of acetylcholinesterase by diisopropylfluorophosphate in 

 the presence of various concentrations of butyrylcholine (BuCh). (From Cohen 

 et al, 1951.) Curve 1: (BuCh) = ml/; curve 2: (BuCh) = 0.6 mM; curve 3: 

 (BuCh) = 1 m3I; curve 4: (BuCh) = 1.25 mM; curve 5: (BuCh) = 2.5 mM; 

 curve 6: (BuCh) = 5 mM; curve 7: (BuCh) > 12.5 mM. 



Once inhibition by the organophosphorus compound has occurred, addition 

 of butyrylcholine will not reverse the inhibition. In such cases, the order of 

 the addition of the inhibitors is very important. The explanation for the 

 protection is simple and the mechanism is much like that involved in pro- 

 tection by the substrate: the reversible inhibitor complexes with the ac- 

 tive site and prevents the organophosphorus compound from reaching the 

 site on a certain fraction of the enzyme molecides, so that following dialysis 

 the butyrylcholine will diffuse away from the fraction of sites it has ])ro- 

 tected. In a similar way, malonate protects succinic dehydrogenase against 

 iodoacetate, heavy metals, and arsenite (Potter and DuBois, 1943; Barron 

 and Singer; 1945; Ackermann and Potter, 1949). 



