INHIBITION OF ENZYMES 



653 



the site of arsenical inhibition, nor has the reaction between arsenicals 

 and lipoate been adequately studied, and there is evidence that perhaps 

 another site must be sought. There is reason to believe that arsenite inhibits 

 dihydrolipoate dehydrogenase by reacting with SH groups on the apoenzyme 

 and that these SH groups are instrumental in the oxidation of the reduced 

 lipoate (Basu and Burma, 1960; Lusty, 1963; Matthews and Reed, 1963). 



Fig. 6-3. Inhibitions of yeast pyruvate decarboxylase 

 by arsenicals. (From Stoppani et al., 1953.) 



It is also interesting that very small quantites of lipoate prevent the inhi- 

 bition of the pyruvate oxidase system by arsenite (Grunert and Rohden- 

 burg, 1960). This does not seem to be due to a reaction with the arsenite 

 since lipoate at only 1/500-1/100 the arsenite concentration is effective. 

 With regard to the failure of arsenicals to inhibit the reduction of ferricya- 

 nide and indophenol dye, one can say only that some pathway not involving 

 lipoate is available, or that the lipoate is protected from attack by arsenite. 

 It is known that the functional lipoate is tightly bound to protein in these 

 systems and this may in some manner make it inaccessible to the inhibitor. 



Inhibition of Cholinesterases 



The problem of whether the cholinesterases are SH enzymes has been 

 much disputed inasmuch as certain SH reagents do not readily inhibit. 

 Arsenicals do inhibit but the pattern is different from that with most 

 enzymes (Table 6-3). The remarkable result is that arsenite is much more 

 potent than the organic arsenicals (R. H. S. Thompson, 1947) and this is 



