The relationship of folic acid to formate metabolism in the rat.

There are many indications that vitamins containing p-aminobenzoic acid (PABA) are concerned with the synthesis of a variety of metabolites (l-16). The mode of action of the PABA-containing vitamins is suggested by the work of Shive et al. (ll), who found that the amine which accumulates in sulfanilamide-treated Escherichiu coli (12) is 5-amino-4-imidazolecarboxamide. The addition of only a single carbon atom is necessary to convert this amine to a purine. It appears that sulfanilamide has blocked the enzymatic addition of this one carbon fragment. It now appears that a common metabolic step in the synthesis of the various metabolites which relieve sulfonamide inhibition or which stimulate growth in PABA-requiring mutant strains of E. coli (13) is a reaction involving formate or one of its derivatives. Several examples may be cited. The carbon of formate is known to be fixed into carbon atoms 2 and 8 of the purine-uric acid (14) (compare the interrelation between folic acid and purines (1, 2, 4, 5)). Serine, which is effective in the partial reversal of sulfanilamide inhibition (B), has been shown by Sakami (15) to be formed in the rat from formate and glycine. Furthermore Holland and Meinke (16) and Broquist and Snell (17) have shown that folic acid promotes the synthesis of this amino acid in bacteria. Glycine in which the a-carbon gives rise to formate (18) stimulates the growth of PABA-less mutants of E. co& (13). Several other examples might be cited in which the evidence for this same interrelationship is suggested but is less well established. As a means of learning more about the function of PABA-containing vitamins, we have investigated the effect of folic acid on the metabolism of formate in the rat.