A study of the relation between folic acid and tissue ascorbic acid.

Many instances of a close relationship between folic acid and ascorbic acid have been reported in the literature. Johnson and Dana (1) have shown that ascorbic acid relieves many of the abnormalities noted in a folic acid deficiency syndrome. Woodruff and Darby (2) have reported that folic acid aids in correcting the abnormal tyrosine metabolism of the scorbutic guinea pig. Nichol and Welch (3, 4) observed that ascorbic acid stimulates the conversion of folic acid by rat liver slices to an essential growth factor for Leuconostoc citrovorum. Recently, Williams (5, 6) has reported that the lowered choline oxidase activity of the livers of rats fed aminopterin is stimulated in vitro by the addition of ascorbic acid. It has also been shown by Williams (7) that the ascorbic acid content of the rat liver is decreased markedly by dietary aminopterin. It was suggested that folic acid or the L. citrovorum factor (LCF) is possibly involved in the maintenance of ascorbic acid in the rat. In the present studies we have investigated this problem further by studying the effect of an aminopterin-induced folic acid deficiency upon the level of ascorbic acid in rat liver and the possible reversal of this effect by supplementing the animals with various levels of folic acid and synthetic LCF. If such a reversal could be effected, the direct involvement of folic acid (or LCF) in the maintenance of tissue ascorbic acid could be demonstrated, although the lack of a reversal by folic acid or LCF would not rule out this possibility, since the utilization of both substances might be inhibited by dietary aminopterin (4, 8).