The relation of folic acid to the metabolism of serine.

The P-carbon atom of n-serine (1) and formia acid (2, 3) were both shown to participate to about the same degree as precursors of the ureide carbons of uric acid. Of all carbon sources investigated these two were used to the highest extent. L-Se&e is also the most efficient known source of glycine in hippuric acid formation (4) and heme synthesis (5), as well as for the 4, 5, and 7 positions of uric acid (1). The reaction leading to the utilization of serine via glycine and a l-carbon fragment is part of a cyclic or reversible process, since glycine can condense with formate, methyl groups of choline, and the a-carbon of glycine itself to give serine (6-9). A possible relation between the metabolism of the p-carbon atom of serine and the function of folic acid is suggested by the finding that the Streptococcus lactis R factor (rhizopterin) has the structure of iV”-formylpteroic acid (lo), and that both the SLR factor and the N’O-formyl derivative of folic acid show folic acid activity for certain organisms (11, 12). In order to determine whether such a relationship exists, L-serine, labeled with Nr5, and sodium benzoate were administered to folic aciddeficient and control rats. Hippuric acid was isolated and its Nls concentration determined. The results (Table I) show that the dilution’ of N16 was 3 times as great in the deficient as in the control rats.2 This could be interpreted to mean (1) that the rate of conversion of serine to glycine is reduced in the deficient rats, or (2) that the amount of glycine available from endogenous sources, in these animals, is greater than normal. The latter possibility was investigated by the same technique with N15-labeled glycine in place of serine. From the results shown in Table