590 12. RATES OF INHIBITION 



cells was about 100 times that in the medium indicating that most of the 

 metal in the tissue is bound to some cell components. Of course, in dia- 

 phragm, or any other tissue, if the respiration is mainly dependent on 

 exogenous glucose, the oxygen uptake will be inhibited because of the 

 depression of glucose uptake into the cells, so that exogeneous glucose res- 

 piration should be more sensitive to Hg"*""*" than endogenous respiration 

 would be. 



The effects of Cu^"^ were different in some respects from those of Hg"*""*" 

 (Fig. 12-31). The latent period in the inhibition of respiration was even 

 more pronounced, perhaps indicating a slower penetration into the cells, 

 but the respiration eventually was inhibited more strongly than the uptake 

 of glucose. It is quite possible in the case of both of these metals that the 

 early binding to the cell membranes gradually altered the permeability 

 properties until the metals could penetrate more readily into the cells. 

 The lag period might then be interpreted as the time required for the mem- 

 branes to be sufficiently damaged to allow penetration. 



{E) Inhibition of cJioI in esterase in erythrocytes. The kinetics of the inhibi- 

 tion of acetylcholinesterase in the red blood cells of the goat were studied 

 by Aldridge (1950), using organic phosphates such as E-600 (p-nitrophenyl 

 diethylphosphate). The inhibition rate followed that expected from a 

 bimolecular reaction where one of the reactants is in excess (Fig. 12-32). 

 There was no evidence at all that the erythrocyte membrane was in any 

 way influencing the course of the reaction, the kinetics being those to 

 be expected if the enzyme were in true solution. When the time to produce 

 50% inhibition was plotted against the reciprocal of the inhibitor concen- 

 tration, a straight line was obtained. An equation related to 12-16 was 

 applied, which is justifiable because of the irreversibility of the inhibition. 

 For 50% inhibition, this equation may be rewritten as: 



kt.Jl) = - In 0.5 = 0.69 (12-87) 



where f „ 5 is the time to produce this degree of inhibition, so that a plot 

 of ?o 5 against 1/(1) should give a straight line with slope 0.69/A-. The rate 

 constant was calculated as 1.1x10^ liters mole^^ min~^. Thus in this case 

 it was possible to investigate accurately the inhibition of an enzyme within 

 cells, demonstrating that penetration factors do not invariably complicate 

 the kinetics. 



RATES OF LETHAL ACTION IN A CELL POPULATION 



When the rate of action of an inhibitor is investigated by determinations 

 of the time course of the lethal effect on a population of cells or organisms, 

 complications are introduced into the interpretation of the data in terms 

 of the primary inhibitory reactions because of the natural variation in the 



