478 THE BIOCHEMISTRY OF B VITAMINS 



obtained. 62 p-Aminobenzoic acid inhibited the growth-promoting action 

 of sulfanilamide in a competitive manner. The ratio of p-aminobenzoic 

 acid to sulfanilamide giving growth inhibition was approximately 0.001. 

 Sulfanilamide was not specific, since sulfapyridine and sulfathiazole also 

 promoted growth. The latter was the most effective. A double mutant 

 obtained from crosses of the sulfonamide-requiring strain and a p-amino- 

 benzoic acid-requiring strain required both p-aminobenzoic acid and 

 sulfanilamide for growth, a maximum being obtained at a ratio of 

 sulfanilamide to p-aminobenzoic acid of approximately 1000. 63 Investiga- 

 tion of this double mutant revealed that low concentrations of p-amino- 

 benzoic acid stimulated the growth of the organism in the absence of 

 sulfanilamide, but that higher concentrations of p-aminobenzoic acid 

 were toxic to the organism. 64 The toxicity of p-aminobenzoic acid at these 

 higher concentrations could be prevented by sulfanilamide. Thus, the 

 sulfonamide-requiring mutant produced more than the tolerated amount 

 of p-aminobenzoic acid. 64 The detrimental enzymatic transformations 

 involved in the utilization of p-aminobenzoic acid are inhibited by sul- 

 fanilamide, which thereby prevents the toxicity of excess p-aminobenzoic 

 acid. A similar situation exists with yeasts for which thiamine is toxic, 

 and the toxicity is prevented by pyrithiamine. 65 



More and more it is being realized that the basis for many of the 

 genetic blocks of enzymatic reactions involves inhibitions by normal 

 metabolic products of the organism. These inhibitions are not unrelated in 

 character to those obtained with synthetic analogues of metabolites. 



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