The effect of folic acid on tyrosine metabolism in guinea pigs.

Several observations in Go have suggested that folic acid may have a role in the oxidation of tyrosine, although no specific function of the vitamin in the metabolism of this ammo acid has been established. Woodruff and Darby (1) and Woodruff et al. (2) found that tyrosyluria, the excretion of p-hydroxyphenyl metabolites of tyrosine, could be corrected in scorbutic guinea pigs, not only by ascorbic acid, but also by the administration of large amounts of folic acid. However, folic acid was not effective in correcting the tyrosyluria in scorbutic monkeys (3,4) and has given inconsistent results in scorbutic human subjects (5-8). Experiments in vitro with folic acid have also produced variable results. Rodney, Swendseid, and Swanson (9, 10) have reported that liver homogenates prepared from rats made folic acid-deficient by being fed succinylsulfathiazole show a decreased ability to metabolize tyrosine, and that the activity was increased by the addition of folic acid. However, other laboratories have been unable to show any impairment of tyrosine oxidation with liver homogenates prepared from folic acid-deficient chicks (11) and rats (12). Rienits (13) found that folic acid stimulated the metabolism of tyrosine with liver homogenates prepared from scorbutic guinea pigs. However, Knox and LeMay-Knox (14) and Williams and Sreenivasan (15) did not observe any effect of folic acid on tyrosine oxidation with dialyzed rat liver homogenates. The present paper demonstrates that the mechanism by which folic acid maintains tyrosine metabolism in tiuo in vitamin C-deficient guinea pigs consists of protecting liver p-hydroxyphenylpyruvic acid oxidase from inhibition and thereby preventing tyrosy\uria. However, in contrast to ascorbic acid, f&c acid and its derivatives have no effect on tyrosine oxidation in vitro, and a possible explanation for these findings will be presented.