Acetylation of Sulfanilamide by Liver Tissue in vitro.

Abstract

Marshall, Emerson and Cutting 1 and Fuller 2 have demonstrated that sulfanilamide is partially converted by man and the rabbit into a conjugated form. The latter has been isolated from the urine of these species after oral ingestion and has been shown to be acetyl sulfanilamide. Ellinger and Hensel 3 have demonstrated the acetylation of para-amino-benzoic acid by the rabbit, and Muenzen, Cerecedo, and Sherwin 4 have concluded that acetylations are very likely confined to the liver.

In an attempt to elucidate the course and site of the acetylation of sulfanilamide, tissue slices of rabbits and rats were suspended in Ringer bicarbonate solution (pH 7.4) containing 0.2% glucose and concentrations of sulfanilamide varying from 10 to 200 mg. %. The mixture was then shaken in a water bath at 37°C. for 4 to 5 hours in an atmosphere of 5% C02 and 95% 02. Samples of the fluid were withdrawn and analyzed for free and conjugated sulfanilamide by the method of Marshall. 5 Of the tissues used (liver, muscle, spleen, kidney, and blood) only the liver could convert sulfanilamide into the conjugated form, and of the preparations used (slices and broken cell suspensions) only the slices were effective. The conjugated form was isolated from the mixture in a crystalline state and was shown to be acetyl sulfanilamide by mixed melting point determinations and by the recovery of the theoretical amounts of acetic acid and sulfanilamide after acid hydrolysis. Conjugation was observed with each of 14 rabbit livers, but with only 2 of 4 rat livers.