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Rat liver slices form from synthetic folic acid (PGA) a factor (CF) utilized for growth by Leuconostoc citrovorum; this conversion is inhibited by aminopterin. In rats given PGA, a similar inhibition of the synthesis of CF is shown by a marked decrease in the urinary excretion of CF following the administration of aminopterin. The antagonist not only prevents the metabolic alteration of PGA but also competes with the product (CF) derived from PGA. The lethal action in rats of aminopterin, 25 μg daily, is not prevented by PGA, but the daily administration of 250,000 units of CF completely counteracts the toxic effects of the antagonist. That CF is a biologically active derivative of PGA is shown by the fact that rats in which growth is arrested by PGA-deficiency, and which due to aminopterin are refractory to PGA, grow remarkably when given concentrates of the citrovorum factor.
Nichol et al. (1950) studied this question.