474 



9. INHIBITION IN CELLS AND TISSUES 



bitioii of each of these enzymes was determined at the time of knockdown 

 (see tabulation). The results show that at the time of death the cholinester- 

 ase was inhibited only moderately whereas the aliesterase was in some 



From Van Asperen (1960). 



cases almost completely inhibited. This might be used as evidence that 

 the lethal action is not related to the inhibition of cholinesterase but of 

 aliesterase. However, this conclusion would be completely unjustifiable. 

 In the first place, we do not know how much of the cholinesterase of the fly 

 must be inhibited so that a marked disturbance would occur in the neuro- 

 muscular system; thus the moderate inhibitions observed on cholinesterase 

 might well be sufficient to cause death. In the second place, the inhibition 

 of the cholinesterase in the tissue or region involved in the lethal action 

 may be different from the over-all inhibition as determined by extracting 

 whole flies. Differences in the distribution of the insecticides or different 

 susceptibilities of the various tissue cholinesterases could account for this. 

 In the third lolace, from what little is known of the role of aliesterases, it 

 might be exi)ected that even complete inhibition would not cause such 

 rapid death. The simple fact that an enzyme is strongly inhibited does not 

 necessarily implicate it in the mechanism and the relationship of this enzyme 

 to the function measured or the life of the organism must be established. 

 If the inhibition of a single enzyme is responsible for an effect, this effect 

 should occur at the same inhibition of the enzyme whatever inhibitor is 

 used; this is not true for either enzyme in the flies. 



QUANTITATIVE EXPRESSION OF INTRACELLULAR ENZYME 



INHIBITION 



The problem now to be considered is this: to what extent can the equa- 

 tions derived for the inhibition of isolated enzymes be applied to inhibition 

 within the living cell? As a corollary to this, it might also be asked if it 

 is possible to determine enzyme and inhibition constants from the study 

 of cells or tissues. The discussion will be restricted to inhibition on a single 



