COMPETITIVE ANALOGUE-METABOLITE INHIBITION 



glutaric acid exerts a "sparing effect" on biotin which results in an in- 

 crease in the ratio of analogue to desthiobiotin necessary for the defined 

 inhibition of growth of Escherichia coli. 20 Since neither cis-aconitic acid 

 nor citric acid exerted such an effect, one would suppose by analogy with 

 the carboxylation of pyruvic acid that biotin functions in the decar- 

 boxylation of oxalsuccinicacid. 20 



Inhibition 

 index 



C0 2 +CH 3 — C— COOH 



7-(3,4-Ureylenecyclohexyl)- 

 butyric acid 



30,000 







HO— C— CH 2 — C— COOH 



O NH 2 



II I 



HO— C— CH 2 — CH— COOH 



Biotin 



Precursor 



Biotin coenzyme 



Inhibition 

 index 



Precursor *- Oleic acid 



300,000 



Inhibition 

 index 



*• Unknown product 



1,000,000 to 



10,000,000 



Figure 5. 



Interrelationships of Biotin Indicated by Inhibition Analysis with 

 7-(3,4-Ureylenecyclohexyl)butyric acid 



Biochemical Functions of p-Aminobenzoic Acid and Folic Acid. Sub- 

 stances other than p-aminobenzoic acid which prevent the toxicity of 

 sulfonamides have been known to occur in natural extracts for some 

 time. 29 - 30 Methionine 30_33 has some ability — which is enhanced by 

 purines 32, 33 — to prevent the toxicity of sulfanilamide for Escherichia 

 coli. Adenine or hypoxanthine is reported to be as active on a weight 

 basis as p-aminobenzoic acid in preventing the protective action of sul- 

 fanilamide against infections of Streptococcus hemolyticus in mice. 34 

 Purines under specific conditions also prevent the toxicity of sulfonamides 

 for lactic acid bacteria 35 and for Eremothecium ashbyii. 3Q 



Such effects of structurally unrelated compounds were early considered 

 to be evidence against the competitive analogue-metabolite theory of 

 sulfonamide action. However, adequate explanations for such action are 



