p-AMINOBENZOIC ACID 489 



tively inactive in preventing the bacteriostasis induced by sulfanilamide 

 for this organism. 65 



These tests have been repeated at various concentrations of sulfanila- 

 mide or sulfathiazole to obtain data which indicate that N-(p-amino- 

 benzoyl)-L-glutamic acid competitively prevents the toxicity of the 

 sulfonamides and presumably is not the metabolic product of the enzyme 

 system inhibited by sulfonamides. 66 



The pronounced activity of p-aminobenzoylglutamic acid over p-amino- 

 benzoic acid has been observed only with two organisms under specific 

 conditions. Even with Streptobacterium plantarum, differences in strains 

 or testing conditions have resulted in failures 67> 68 > 69 to duplicate the 

 results of Auhagen. 65 One such result is indicated in Table 3. However, 

 p-aminobenzoylglutamic acid is indicated in the same table to be con- 

 siderably more effective than p-aminobenzoic acid for Lactobacillus 

 arabinosus, but only in preventing the toxicity of low concentrations of 

 sulfapyridine. 69 However, adaptation to grow without p-aminobenzoic 

 acid occurs under such conditions and may account for the unusual ac- 

 tivity. At higher concentrations of inhibitor, p-aminobenzoylglutamic 

 acid becomes relatively ineffective. 69 



In promoting growth of Lactobacillus arabinosus, p-aminobenzoyl- 

 glutamic acid is only about 25 per cent as effective as p-aminobenzoic 

 acid after 20-24 hours' incubation, but approaches the activity of 

 p-aminobenzoic acid after 64 hours' incubation (77 per cent). 69, 70 



In preventing the bacteriostasis resulting from the action of sulfanila- 

 mide on Escherichia coli, Clostridium acetobutylicwm, Streptococcus 

 pyogenes, Diplococcus pneumoniae Type I, and Lactobacillus arabinosus, 

 N-(p-aminobenzoyl)-L-glutamic acid is only 0.017, 0.012, 0.25, 0.1 and 

 5.0 per cent, respectively, as effective as p-aminobenzoic acid. 68 The glu- 

 tamate is only 0.067 and 0.13 per cent as effective as p-aminobenzoic acid 

 in promoting the growth of Clostridium acetobutylicum and Acetobacter 

 suboxydans, respectively. 68 N-(p-Aminobenzoyl)-L-glutamic acid is also 

 less active than p-aminobenzoic acid in preventing the toxicity of sulfa- 

 pyridine for Diplococcus pneumoniae Type III and Streptococcus hemo- 

 lytics Group A, 16 and the toxicity of sulfadiazine for Streptococcus 

 faecalis Ralston and Streptococcus zymogenes 26 CI. 



While the enhanced activity of N-(p-aminobenzoyl)-L-glutamic acid 

 over p-aminobenzoic acid is not widespread, the results with a single 

 organism gave an early indication of the involvement of glutamic acid 

 in the metabolism of p-aminobenzoic acid. With the discovery of p-amino- 

 benzoic acid as a constituent of folic acid, the presence of glutamic 

 acid in the folic acid molecule became an obvious possibility. 



