The Mode of Action of 7-Methyl Folic Acid

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Abstract
To determine the mode of action of folic acid antagonists, various agents were used to counteract the growth-inhibiting action of sulfonamides and folic acid displacers. Staphylococcus aureus #209 was the test organism. Sulfathiazole appeared to prevent the incorporation of p-aminobenzoic acid into pteroic acid. Pteroylglutamic acid did not counteract the sul-fonamide indicating it is involved in Staphylococcus metabolism. Pteroic acid was more effective than p-aminobenzoic acid in counteracting sulfathiazole. Methyl folic acid was counteracted by pteroylglutamic acid, pteroic acid, and p-aminobenzoic acid but not by p-aminobenzoyl-l(+)-glutamic acid, indicating synthesis of pteroic acid as the first step in the formation of pteroylglutamic acid. Pteroic acid, p-aminobenzoic acid, and pteroylglutamic acid were equally effective on a molar basis in counteracting methyl folic acid. Methyl folic acid may interfere with synthesis of pteroylglutamic acid at the stage of pteroic acid formation and at the stage of union with glutamic acid. It can displace formed pteroylglutamic acid. The counteraction of methyl folic acid by sulfathiazole indicates similarity of structure resulting in mutual interference superseding that of interference with the metabolism of pteroylglutamic acid.
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