644 



13. REVERSAL OF INHIBITION 



Inhibition reversals whose rates are limited by the dissociation of the 

 EI complex probably occur but apparently are not too common. In cell 

 suspensions or tissue slices exposed to mercurials or arsenicals and then 

 resuspended in inhibitor-free media, one might predict that the rate at 

 which metabolic activity is restored would be primarily dependent on the 

 splitting of the inhibitor from the enzymes, but the exjjeriments of Fink 

 and Wright (1948 a, b) on the binding of oxophenarsine to erythrocytes 

 indicate that the situation may be more complex. Rabbit erythrocytes 

 previously incubated with different concentrations of oxophenarsine were 

 resuspended at half-hourly intervals in fresh plasma and the amounts 

 of arsenical released during each period were determined. The results are 

 shown in Table 13-2. The binding of oxophenarsine was mainly reversible 



Table 13-2 



Release of Oxophexarsine from Rabbit Erythrocytes Resuspended 



IN Normal Plasma " 



" The release is calculated as the percentage of the theoretical amount released 

 assuming complete reversibility. The concentrations of oxophenarsine to which the 

 erythrocytes were previously exposed are given at the heads of the columns. From 

 Fink and Wright (1948 a). 



but by no means complete at 90 min and the fraction that was not released 

 increased with the concentration of the arsenical. It is clear that there are 

 different binding sites for the oxophenarsine in the erythrocytes. From 

 some of these sites the arsenical is relatively rapidly dissociated but from 

 other sites only very slowly. No enzymic studies were carried out and con- 

 sequently it is not known in what category the enzyme sites should be plac- 

 ed. They then showed that oxophenarsine dialyzed c^uite readily from 

 serum but much mor.e slowly from blood. However, if the erythrocytes 

 were hemolyzed with saponin, the dialysis of the arsenical was increased; 

 destruction of the cell membrane increased the percentage dialyzing in 6 

 hr from 33% to 59%. This could be interpreted as a barrier to diffusion im- 

 posed by the cell membrane. Thus both dissociation and diffiusion factors 

 would be implicated. Certain inhibitors whose actions on cells or tissues are 



