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A. D. WELCH AND E. BUEDING 



than the parent substance, a metabolic alteration which obviously 

 cannot be termed "detoxication." 



As with the other mechanisms of metabolic alteration, conjuga- 

 tion does not necessarily result in a reduction in toxicity. Thus, 

 acetylation of sulfonamides renders these compounds not only thera- 

 peutically useless but also more toxic. Conjugations of other foreign 

 compounds with acetic, sulfuric, or glucuronic acids, or with glycine, 

 glutamine, or cysteine, may result, however, in true detoxications. 

 As yet, little is known about the mechanisms and enzymic reactions 

 involved in most conjugations. Conceivably, conjugation-reactions 

 may be enhanced by supplying the organism with the acids which are 

 found in combination with the foreign compounds, or with the pre- 

 cursors of the acids. Acetic acid (15), glycine (11,31), and sulfuric acid 

 (1) are used directly for conjugation, while three-carbon compounds, 

 rather than free glucuronic acid itself, are involved in the formation of 

 glucuronides (16). If a compound is conjugated with more than one 

 acid, one conjugate being more toxic than the other, a favorable result 

 might be attained by increasing the availability of the precursor of 

 the less toxic conjugate. Thus, it might be possible that the poten- 

 tially harmful acetylation of sulfonamides might be inhibited to some 

 degree if glucuronic acid conjugation (28,32,36) could be favored. 



The striking decrease in the toxicity of certain pentavalent 

 arsenicals which results from the simultaneous administration of p- 

 aminobenzoic acid is at present an unexplained type of detoxication 

 (29). Although the decrease in the toxicity of such compounds is 

 accomplished without inhibition of trypanocidal action, it has been 

 shown (14,24) that the action of the arsonic acid derivative, atoxyl, 

 on Escherichia coli is antagonized by j&-aminobenzoic acid, in the same 

 manner as are the sulfonamides. Since the mammalian toxicity of 

 the sulfonamides is not antagonized by ^-aminobenzoic acid, it seems 

 unlikely that the pentavalent arsenicals influence an undetected 

 function of /?-aminobenzoic acid in animal tissues, unless, by virtue 

 of their different distribution, systems are affected on which the sulfon- 

 amides are inert. A study of the effect of /?-aminobenzoic acid on iso- 

 lated enzyme systems may throw light on the mechanism of this de- 

 toxication. 



Discussion of the detoxication of the arsenicals would not be 

 complete without mention of the detoxifying action of sulfhydryl- 



410 



