METABOLITE ANTAGONISTS 239 



compounds is unknown, but the possibility of inhibition should be kept 

 in mind when only a few amino acids are used in a medium. The effect 

 of any single compound upon a fungus may be modified by the other 

 constituents of the medium. 



Harteiius (1946a) found glutamic and aspartic acids, glutamine, and 

 asparagine to inhibit the growth of a strain of yeast when suboptimumal 

 amounts of /^-alanine were used in the medium. These amino acids did 

 not inhibit growth when pantothenic acid was used. In fact, these com- 

 pounds stimulated growth under these conditions. The inhibitory effect 

 in the presence of /3-alanine was overcome by increasing the concentration 

 of this provitamin. To obtain maximum growth in the presence of 50 

 mg. of glutamic acid per flask (55 ml.), twenty times as much j9-alanine 

 was required as when glutamic acid was omitted from the medium. 

 Harteiius attributed this effect to the combination of /3-alanine and 

 glutamic acid to form an inactive dipeptide. 



Among the naturally occurring amino acids, L-canavanine is found 

 free in jack beans. Canavanine is an analogue of arginine; the formulas 

 are shown below. 



HjN— C(=NH)— NH— CH2— CH2— CH,— CH(NH2)— COOH 



Arginine 



H2N— C(=NH)— NH— O— CH2— CH2— CHCNH,)— COOH 



Canavanine 



Horowitz and Srb (1948) studied the effect of canavanine on three 

 wild-type strains of Neurospora and found one strain to be inhibited 

 completely by concentrations greater than 1.25 mg. per liter; another 

 strain was only partially inhibited, while the third strain was tolerant. 

 Genetic analysis indicated that tolerance and susceptibility segregated 

 by alternative forms of a single gene. L-Arginine was effective in over- 

 coming canavanine toxicity, while L-lysine was less effective. Three 

 molecules of arginine overcame one molecule of canavanine in the strain 

 of Neurospora most sensitive to this inhibitor. A similar competitive 

 inhibition between canavanine and arginine in various bacteria has also 

 been observed (Volcani and Snell, 1948). 



Other metabolite antagonists. Woolley (1944a) found benzimidazole 

 to inhibit the growth of Saccharomyces cerevisiae and Endomyces vernalis. 

 This inhibition was overcome by adenine and guanine. The structural 

 relationship between benzimidazole and adenine is shown below: 





N=C— NH2 



HC C— NH 



\ 

 CH 



— C— N 

 Benzimidazole Adenine 



