STRUCTURE AND ACTIVITY 463 



endogenous respiration increased; both processes generate an increase 

 in oxygen uptake (52, 67, 145, 331, 446). In view of the generally non- 

 specific action of the phenols as a group (29), nitrophenols probably 

 exert still other effects on cells. 



The reagents which inactivate sulfhydryl enzymes form a second cate- 

 gory, in which the specificity is toward the group of enzymes rather than 

 toward any one, although differences in sensitivity are common. Free 

 sulfhydryl groups on an enzyme or other protein can be inactivated by 

 any of several reactions (21, 94, 95, 306, 316, 455): 



1. Alkylation by, e.g., iodoacetic acid. The product may be visual- 

 ized as a thioether structure on the enzyme surface. 



2. Oxidation of two nearby sulfhydryl groups to a disulfide. Ferri- 

 cyanide, iodosobenzoic acid and, presumably, almost any mild oxidizing 

 agent can effect this type of inactivation. Thiols protect against this 

 reaction. 



3. Mercaptide formation. The characteristic agents of this reaction 

 are heavy metals and trivalent arsenicals; one of the most specific poi- 

 sons of this type is p-chloromercuribenzoic acid (316). Thiols protect 

 also against these agents. 



4. Addition reactions. These have been postulated particularly to 

 explain enzyme inactivation by quinones and other «,/3-unsaturated 

 compounds. 



Although none of these four types of reaction is certainly known to be 

 responsible for the action of fungitoxicants, it will be seen later that 

 mercaptide formation can be invoked as a possible mechanism for the 

 action of heavy metals against fungi, and that the fungistatic quinones 

 may act either by oxidation or by addition reactions to sulfhydryl 

 groups. 



The third group is the most amorphous of all — compounds which 

 are so generally reactive that they may be expected to inactivate a va- 

 riety of enzymes, possibly by more than one reaction. As mentioned 

 later, the quinones may belong to this group rather than to the class of 

 toxicants affecting sulfhydryl enzymes only. The action of 2,4-dichloro- 

 6-(o-chloroanilino)-5-triazine and its relatives (447) is presumably of 

 this type. Amino acids and peptides are alkylated by an exchange re- 

 action for which the chlorine atoms attached to the heterocyclic ring 

 are responsible, and both sulfhydryl and amino groups are alkylated 

 (50). 



As discussed in the section on selective accumulation, many fungicides 

 are active only after a large amount of the toxicant is bound by the 

 cell. This suggests, as McCallan (246) points out, that most fungistatic 



