572 5. QUINONES 



asparagine, are able to antagonize the action of the quinone, and this may 

 be related to the synthesis of cofactor. It is unfortunate that this work 

 was not carried further and that this type of investigation is rare in these 

 fields, since it is only by quantitative analysis of the compositional changes 

 occurring during the actions of growth inhibitors that one can approach 

 the site or sites of inhibition. 



Woolley (1945 a) studied the actions of 2,3-dichloro-l,4-naphthoquinone 

 on various microorganisms in order to determine if it is an antagonist of 

 vitamin K. Menadione was examined for its ability to reverse the inhibition 

 by 2,3-dichloro-l,4-naphthoquinone. A difficulty lies in the fact that men- 

 adione is quite a potent inhibitor itself, depressing growth 50% at 0.0013- 

 0.0016 mM in the case of yeast and Endomyces vernalis. However, mena- 

 dione, at concentrations around one tenth of this reduced the inhibition by 

 2,3-dichloro-l,4-napthoquinone and this was claimed to be competitive 

 over a limited concentration range. No such inhibition reversals with men- 

 adione were seen in the four bacterial species studied. Hoffmann-Ostenhof 

 et at. (1947 b) could not confirm this antagonism in yeast, but later some 

 antagonism was observed (Hoffmann-Ostenhof and Fellner-Feldegg, 1949 a). 

 Guerillot-Vinet and Guerillot-Vinet (1948) observed an antagonism by 

 menadione of the growth inhibition of Fusarium solani by 2-chloro- and 

 2-methoxy-l,4-naphthoquinones, and Molho and Lacroix (1950) found the 

 same for Aspergillus niger. In the latter case, the inhibition over 10 days 

 by menadione at 0.071 mM was 68%, by 2-chloro- 1,4-naphthoquinone at 

 0.065 mM 95%, and by both together at the same concentrations only 

 27%. These results are not as easy to interpret as some other antagonisms. 

 For example, if menadione is normally functional in the metabolism of 

 these fungi, what is the mechanism for its inhibition of growth? And why 

 is its inhibition reduced by the chlorinated naphthoquinone? The answer 

 to these and other questions will come only when we have information on 

 the role of naphthoquinones in fungal metabolism, and data on the effects 

 of inhibitory quinones on isolated enzyme systems. 



The inhibitions of spore germination and the pyruvate decarboxylase of 

 Monilinia fructicola by various naphthoquinones are of the same order of 

 magnitude (see accompanying tabulation), and this suggested to Foote 

 et al. (1949) that this enzyme might be a major site of action. The relatively 

 low potency of 1,4-naphthoquinone in inhibiting germination was attributed 

 to its high reactivity, much of it being bound. Despite the discrepancies, 

 this is certainly one of the few convincing correlations that have been made 

 in this field, and furthermore implicates an enzyme of undoubted impor- 

 tance in metabolism. In support of this site of action, one recalls the ac- 

 cumulation of pyruvate in Fusarium lini induced by low concentrations 

 of 1,4-naphthoquinone (Maselli and Nord, 1952) (Fig. 5-5), It would be 

 interesting to know more about the reactions of 2,3-dichloro-l,4-naphtho- 



