D. W. WOOLLEY 



the receptor portion of an enzyme. The enzyme was supposed to 

 require />-aminobenzoic acid as a coenzyme, and the introduction of a 

 sulfonamide was supposed to result in a firm combination of the latter 

 with that portion of the enzyme to which /^-aminobenzoic acid normally 

 would be attached. The resultant foiling of the enzyme was said to 

 be overcome by an increase in the concentration of /?-aminobenzoic 

 acid which would shift the equilibrium in favor of the j&-aminobenzoic 

 acid-enzyme combination. Despite the fact that there has been no 

 direct experimental proof of an enzyme system involving p-amino- 

 benzoic acid, this attractive hypothesis has continued to flourish with 

 but slight opposition. Its chief buttresses have been the competitive 

 nature of the relationship between /^-aminobenzoic acid and the 

 sulfonamides, the success realized in application to other metabolites 

 of the same idea of structurally related inhibitors, and the lack of a 

 better hypothesis. A similar explanation has been given for the be- 

 havior of other inhibitory analogues. Since some of the metabolites 

 concerned with these antagonists are known to function as coenzymes 

 in well-defined enzyme systems it would seem advisable to put the 

 hypothesis in these instances to experimental test. There are some 

 shreds of evidence that are exceedingly difficult to fit into the original 

 postulate. For example, it has been noted with the sulfonamides, 

 with pyrithiamin, and with benzimidazole that subinhibitory quan- 

 tities of the compounds actually stimulated the growth of micro- 

 organisms. If the coenzyme replacement hypothesis is correct, it is 

 difficult to understand this stimulation. Furthermore, when resting 

 bacterial cells were treated with sulfonamides or with thiopanic acid, 

 no /?-aminobenzoic acid or pantothenic acid was liberated. This 

 observation, however, does not overthrow the hypothesis because the 

 amounts of metabolite liberated (either /j-aminobenzoic acid or panto- 

 thenic acid) may have been below the detectable amount, or may 

 have been retained inside the cells. 



Much has been written about whether the antagonism with 

 /)-aminobenzoic acid explains the action of the sulfonamides in the 

 production of bacteriostasis and in the cure of certain infectious 

 diseases. Whatever the true explanation of the action may be, the 

 following must not be forgotten. First, /?-aminobenzoic acid reverses 

 competitively the effect of the sulfonamides, and second, j&-amino- 

 benzoic acid is a metabolite for microorganisms. In the light of these 



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