162 CHEMICAL AGENTS 



analogues of vitamins (Chapter 10) and amino acids (Chapter 8). 

 Horsfall (174) lists in convenient form a number of examples. 



A few of the more active fungicides are conceivably metabolite ana- 

 logues competing with normal substrates or coenzymes, but in no in- 

 stance has the action of such a fungicide been explained on this basis. 

 Inhibition by 2,3-dichloro-l,4-napthoquinone is reversed by vitamin K 

 (453), but there is no evidence that the vitamin is essential to fungi. 

 Simple reversal experiments, inconclusive in themselves, have been the 

 bases of suggestions that 2-heptadecyl-2-imidazoline interferes competi- 

 tively with purine biosynthesis (438), that ascosin is a fatty acid anti- 

 metabolite (154), and that propionic acid interferes with acetate me- 

 tabolism (155, 156, 326). 



Inhibition of Enzymes. Present-day biology relies in perhaps too 

 great measure on the findings of enzymology. Toxicants to which no 

 specific role can be assigned are often stated to affect some, unspecified, 

 enzyme or enzymes; such a statement is more an article of faith than an 

 hypothesis. 



However, there is no doubt that toxicants do affect enzymes, and we 

 may distinguish three classes in relation to fungi: (1) agents which act 

 specifically by inhibition of one essential enzyme system; (2) agents 

 which act on sulfhydryl enzymes as a group; and (3) agents whose de- 

 monstrable reactivity with proteins suggests that they act on enzymes 

 in general. This classification may be considered either as based on 

 decreasing specificity of the fungicide or on our increasing ignorance. 



The first group — compounds which owe their toxicity to inhibition 

 of a single enzyme system — is exemplified by the antimycins, antibiotics 

 produced by Streptomyces sp. (96, 231). These interfere specifically 

 with electron transport in the cytochrome system (63, 335, 343, 421). 

 Antimycin may affect other electron-transport systems also (305). Ob- 

 viously, the specifically antifungal activity of the antimycins cannot be 

 explained on this basis alone, since most organisms depend on the cyto- 

 chrome system. 



The action of the so-called uncoupling agents — 2,4-dinitrophenol and 

 3,5-dinitro-o-cresol are examples — cannot be specified so narrowly as 

 that of the antimycins. It appears that they prevent the oxidative 

 phosphorylations which are associated with the transfer of electrons 

 from substrate to oxygen (233, 379, 380, 412). The effect is to liberate 

 respiration from the control normally imposed upon it by phosphate 

 storage compounds of the cell, and at the same time inhibit reactions 

 which are driven by the hydrolysis of phosphorylated intermediates. 

 Operationally, it is found that oxidative assimilation is suppressed or 



