p-AMINOBENZOIC ACID 513 



venting the inhibition. The effect of the sulfonamides on cytochrome c, 

 cytochrome c reductase, and lactic dehydrogenase is much less pro- 

 nounced, and cytochrome oxidase is not affected. 258 p-Aminobenzoic acid 

 and a number of other aromatic acids are reported to inhibit lactic acid 

 dehydrogenase. 259 



Sulfathiazole is reported to inhibit to a greater extent than other sulfon- 

 amides the anaerobic decarboxylation of pyruvic acid by Staphylococcus 

 aureus, Escherichia coli and yeast. 260 The partial inhibition of carboxylase 

 of yeast or Staphylococcus aureus is prevented to some extent by cocar- 

 boxylase 261 and to a greater extent by p-aminobenzoic acid. 262 p- Amino- 

 benzoic acid at higher concentrations was inhibitory to carboxy- 

 lase. 261, 262, 263 It was considered that these results provided additional 

 evidence for the hypothesis that the mode of action of sulfonamides 

 involves the respiratory enzymes. 



Although sulfonamides have been reported to inhibit the oxidation of 

 glucose, 246 - 255 ' 256 - 263 - 264 > 265 glycerol, lactate and pyruvate, 266 " 267 inhibi- 

 tions of respiration by sulfonamides appear to be either unrelated or at 

 most indirectly related to the inhibition of the catalytic role of p-amino- 

 benzoic acid. 



Effects on Nutrition of Animals. Certain sulfonamides fed to rats in 

 a highly purified diet which alone supports normal growth and develop- 

 ment cause the appearance of typical signs of dietary deficiencies. 268-272 

 These symptoms often do not develop in animals receiving the sulfona- 

 mide in stock or natural diet. 272 - 273 Although the mechanism by which 

 sulfonamides exert such an effect is not completely understood, experi- 

 mental evidence has usually been interpreted as indicating that the defi- 

 ciencies develop as a result of the bacteriostatic action of the sulfonamides 

 on the intestinal bacteria which synthesize certain factors required by 

 the animals. The intestinal flora is usually markedly affected in animals 

 receiving sulfonamide. 



The symptoms which develop on administration of sulfaguanidine or 

 succinylsulfathiazole in highly purified diets to rats include alopecia, 

 achromotrichia, porphyrin-stained whiskers, anemia, leukopenia, agranu- 

 locytosis and hypocellularity of the bone marrow. These symptoms, as 

 well as the retardation in growth and increase in prothrombin time which 

 result from the toxic action of the sulfonamides, are overcome by supple- 

 ments of folic acid and biotin. 271, 273 - 279 Vitamin K counteracts only the 

 prothrombin effect. 274 - 275 p-Aminobenzoic acid prevents the effect of 

 sulfaguanidine, 268-274 but is reported not to counteract the effect of suc- 

 cinylsulfathiazole. 272 



The hepatic storage of folic acid and biotin decreases in rats on a 

 highly purified diet as compared with stock or natural diets; however, 



