TWO INHIBITORS ACTING ON A SINGLE ENZYME 



493 



Such potentiation of fluoride inhibition by phosphate must be of signifi- 

 cance in the intracellular inhibition of succinic dehydrogenase by flouride, 

 where the phosphate concentration is unknown and may vary under dif- 

 ferent conditions. 



lOOOmM 



(FLUORIDE) 



Fig. 10-1. Inhibition of succinic dehydrogenase by fluoride at various concentrations of 

 phosphate. The curves are plotted from Eq. 10-16 using the constants given by Slater 

 and Bonner (1952): K^ = 0.48 mM, K^ = 100 mM, K, = 20 mil/, A%/ = 0.067 

 mM, (S) = 10 mM, and a = 0.00335. Curve 1: (P) = 200 mM; curve 2: (P) = 100 

 mM; curve 3: (P) = 50 mM; curve 4: (P) = 10 mM; curve 5: (P) = mM. 



Other Examples of Multiple Inhibition 



The reversible cholinesterase inhibitors, physostigmine and neostigmine, 

 can protect the enzyme against the organophosphorus compounds (Koelle, 

 1946), both in vitro and in vivo (Koster, 1946). Butyrylcholine is also a re- 

 versible competitive inhibitor of cholinesterase and the quantitative as- 

 pects of its effects on inhibition by diisopropylfluorophosphate were stud- 

 ied by Cohen et al. (1951). In one experiment in which the enzyme in the 

 presence of butyrylcholine was incubated for 10-20 min with diisopropyl- 

 fluorophosphate, the protection provided by the former compound rose 

 with its concentration (see tabulation). In other experiments, the protection 



