512 THE BIOCHEMISTRY OF B VITAMINS 



Effect on Respiration. Since the early indication 243> 244 that sulfon- 

 amides inhibit the respiration of certain bacteria and other microorgan- 

 isms, numerous investigators have attempted to correlate inhibition of 

 respiration with inhibition of growth by sulfonamides. While both inhibi- 

 tions occur simultaneously in some organisms, 244-246 the inhibition of 

 growth of most organisms by sulfonamides appears to involve essential 

 metabolic reactions not directly associated with respiration. 247 Respira- 

 tion is inhibited by certain sulfonamides which are without chemothera- 

 peutic activity. 248 



The inhibition of growth of Staphylococcus aureus by sulfapyridine 

 is reported to be prevented partially by coenzymes I or II, but not by nico- 

 tinic acid. 249 The ability of these coenzymes to prevent the toxicity of 

 sulfapyridine has been questioned on the basis of failures to confirm this 

 effect with both Staphylococcus aureus and a strain of Escherichia coli 

 requiring nicotinic acid for growth. 250 However, it has been shown that 

 the ability of coenzyme I to exert such an effect on Staphylococcus aureus 

 is dependent on the use of a small inoculum, and apparently is related 

 to the growth-stimulating action of the coenzyme. 251, 252 High concentra- 

 tions of nicotinic acid (100 y per cc) are reported to prevent the toxicity 

 of low concentrations of sulfapyridine for Lactobacillus arabinosus. 253 

 Nicotinamide, cozymase, and nicotinamide-riboside exert a similar effect 

 at somewhat lower concentrations (1 to 5 y per cc) in preventing the 

 toxicity of sulfapyridine (2 y per cc). 253 



Some attempts were unsuccessful in demonstrating interference of 

 sulfanilamide, sulfapyridine or sulfathiazole in the functioning of 

 cozymase in yeast fermentation and in several systems in rat liver. 254 



However, sulfapyridine appears to inhibit competitively the stimula- 

 tion by nicotinamide of the respiration of nicotinamide-deficient cells of 

 dysentery bacilli utilizing glucose. 255-257 Greater inhibitory activity was 

 observed if the sulfapyridine was added prior to the vitamin. Similar 

 results were obtained with cozymase; but since p-aminobenzoic acid did 

 not affect the inhibition, the inhibitory action does not appear to be 

 related to growth inhibitions which are prevented by p-aminobenzoic 

 acid. Other sulfonamides showed no definite inhibition of nicotinamide- 

 stimulated respiration. 255-257 



The sulfonamides, particularly sulfanilamide, prevent the combination 

 of coenzyme II with the apoenzyme from yeast which oxidizes glucose- 

 6-phosphate to phosphohexonic acid. 258 The sulfonamides react irrevers- 

 ibly with the apoenzyme and compete with the prosthetic group for the 

 apoenzyme. Coenzyme II counteracts approximately fifty times its con- 

 centration of sulfanilamide. Glucose-6-phosphate also counteracts the 

 inhibition to some extent, but p-aminobenzoic acid is ineffective in pre- 



