482 THE BIOCHEMISTRY OF B VITAMINS 



mide led to indirect evidence suggesting that inactivation of essential 

 enzymes was involved. 9, 10 Extracts of streptococci, 11 Brucella abortus 12 

 and yeast x were effective in preventing the toxicity of sulfanilamide for 

 streptococci ; and the active substance from yeast extract reversed inhibi- 

 tion in a manner reminiscent of the competitive inhibition of enzyme 

 reactions by substances structurally related to the substrate. 1 By testing 

 substances structurally related to sulfanilamide, Woods x discovered that 

 p-aminobenzoic acid was extremely effective in preventing competitively 

 the toxicity of sulfanilamide, and that the compound exhibited a high 

 degree of specificity. 



S0 2 NH 2 



I 



NH 2 NH 2 



p-aminobenzoic acid sulfanilamide 



It was proposed that p-aminobenzoic acid is an essential metabolite 

 synthesized in adequate amounts by many organisms but that it might be 

 an essential growth factor for some organisms. 1 



Within a short time the nutritional importance of the compound was 

 demonstrated by Rubbo and Gillespie, 13 who isolated p-aminobenzoic 

 acid as the N-benzoyl derivative from yeast, and demonstrated that 

 p-aminobenzoic acid is an essential growth factor for Clostridium aceto- 

 butylicum. p-Aminobenzoic acid was subsequently isolated from yeast 

 in the free form and as the N-acetyl derivative by Blanehard, 14 and as the 

 methyl ester by Kuhn and Schwartz. 15 Many other organisms were sub- 

 sequently shown to require this factor. 



Specificity 



The specificity of the nutritional requirements of various organisms 

 for p-aminobenzoic acid, as well as the specificity of this substance in 

 preventing the toxicity of sulfonamides for various organisms, is indicated 

 in Table 2, in which the activities of various compounds related to 

 p-aminobenzoic acid are listed. 



A majority of the compounds which possess activity in replacing 

 p-aminobenzoic acid are substances which presumably can be easily con- 

 verted to p-aminobenzoic acid by the various organisms. These include 

 4-aminocyclohexanecarboxylic acid, p-nitrobenzoic acid, p-hydroxylami- 

 nobenzoic acid, N-glycosido-p-aminobenzoic acids, esters and certain 

 amide derivatives of p-aminobenzoic acid — all of which can be converted 



