Effect of 4-Amino Folic Acid Antagonists on Biological Acetylations.

Publisher Website
Google Scholar
Abstract
A methopterin (10-5 [image]) and aminopterin (5 x 10-5 [image]) inhibited (non-competitively) the acetylation of sulfanilamide by pigeon liver extracts 62 and 58% respectively. Acetylation of isoniazid was similarly inhibited. Folic acid and 2,4-diaminopteridine, at 10-3 [image] concentration, were not inhibitory, and failed to reverse the inhibition by A-methopterin. 2,4-Diamino-6,7-diphenylpteridine (10-3 [image]) inhibited acetylation 50%. The activation of acetate to acetyl-5-CoA was inhibited 33-36% by 10-4 [image] A-methopterin. The latter, administered to rabbits conjointly with sulfanilamide, produced a marked increase in plasma level of free sulfanilamide, and a concomitant decrease in acetyl-sulfanilamide. These results suggest a mechanism of action of folic acid antagonists distinct from their effect on formation and utilization of citrovorum factor.