ACTION OF FUNGICIDES 251 



of mercuric ion is to cause stasis, which may be reversed by treating the 

 cells with reagents which have a high affinity for mercury. McCalla 

 (1940) demonstrated that cells of Escherichia coli which had been treated 

 with mercuric chloride could be revived by hydrogen sulfide. If stasis 

 due to mercury is not overcome within a certain time, irreversible changes 

 occur and death of the cells results. 



Organic mercury compounds are not protein precipitants, and this is 

 one of their advantages as disinfectants and fungicides. Fildes (1940) 

 ascribed the action of mercury compounds to combination of mercuric 

 ion with the sulfhydryl group of essential metabolites and enzymes. 

 Others have shown that organic mercury compounds act similarly. 

 According to this view, enzyme inhibition is the basis of the action of 

 mercury compounds. Fildes found that the action of mercury was 

 antagonized by compounds which contained free sulfhydryl groups 

 (thioacetate, cysteine, glutathione). Neither cystine ( — S — S — ) nor 

 methionine ( — S — ) was effective in overcoming mercury toxicity. 



Organic mercury compounds appear to act by the same mechanism as 

 the mercuric ion. p-Chloromercuribenzoate was found to inhibit the 

 action of various sulfhydryl enzymes which take part in carbohydrate 

 metabolism, e.g. succinic acid oxidase, yeast carboxylase, malate oxidase, 

 and ketoglutarate oxidase. This organic mercury compound also inhib- 

 ited the action of c?-amino acid oxidase, transaminase, Z-glutamate oxidase, 

 and other enzymes (Barron and Singer, 1945; Singer and Barron, 1945). 

 In many instances the inhibitory action of p-chloromercuribenzoate on 

 these enzymes could be reversed by glutathione, cysteine, or hydrogen 

 sulfide. 



Cook et at. (1946) found phenylmercuric nitrate to depress the respira- 

 tion of Saccharomyces cerevisiae. This depression in rate of respiration 

 was overcome by various compounds having a free — SH group; e.g., 

 cysteine and homocysteine, while cystine and methionine were without 

 effect. The work of these investigators and of others makes it highly 

 probable that mercury compounds are toxic because they inactivate 

 certain essential enzyme systems. The enzyme inhibitions discussed 

 above are examples of noncompetitive inhibition. These inhibitions are 

 reversible, as in the case of competitive inhibition, but the reversing 

 agents are nonspecific, or not limited to a single metabolite. 



SULFUR 



Of the nonmetallic elements, sulfur and certain of its compounds are 

 widely used as protective and eradicant fungicides. The toxicity of the 

 nonmetallic elements is dependent upon the state of oxidation. In many 

 instances, compounds in the higher states of oxidation are the least toxic. 

 For example, sulfur in the form of the free element (S) and of sulfide 



