280 1. lODOACETATE AND lODOACETAMIDE 



acetate acts very similarly, whereas ethyl chloroacetate is considerably less 

 potent, indicating the importance of the halogen atom. These esters are 

 more potent respiratory inhibitors than cyanide, but it seems that in yeast 

 only about 50% of the respiration in sensitive. The inhibition of respiration 

 is rapid so that hydrolysis is probably not a factor here, but over several 

 hours the inhibition disappears, which may be the result of hydrolysis. 

 The respiration of frog skin and muscle is less sensitive than that of yeast 

 to ethyl bromoacetate, 50% inhibition being given by 0.12 mM in the 

 former and 0.24 mM in the latter (Fleckenstein et al., 1950). However, 

 one finds the same differential effects on respiration as in yeast. Fleckenstein 

 believed that these esters must be classed as cycle inhibitors and demon- 

 strated that several enzymes of the cycle are inhibited. Just et al. (1951) 

 investigated the effect of bromoacetate esters of different chain length on 

 yeast respiration and found even more potent inhibition than in the pre- 

 vious work (see accompanying tabulation). In the «-bromopropionate series 



Concentration for t^ , ^• 

 T^ ^r, /.,.,. • Kelative 



Bromoacetate ester 50% inhibition 



of esters, the ethyl ester is also the most potent inhibitor of respiration, 

 but is about one fourth as active as the bromoacetate ester. All of these 

 results indicate clearly that the esters can presumably act directly and not 

 entirely by release of the haloacetates. 



Is is interesting that the amides and the esters act so differently, since 

 this demonstrates that it is not simply a matter of the removal of the neg- 

 atively charged carboxylate group. It is rather surprising that more work 

 on the mechanisms of the respiratory inhibition has not been done, especially 

 as these esters might well be valuable inhibitors for selective effects on 

 certain pathways of metabolism. A few suggestions for those using such 

 inhibitors may be made, inasmuch as the past studies have not usually 

 included the data necessary to allow interpretation. Proper controls with 

 the unsubstituted esters of acetate or propionate should be run to evaluate 

 the role of the halogen atoms. The kinetics of the inhibitions should be 

 followed closely, preferably with data on the hydrolytic rates for the esters. 



