Formation of 10-formylfolic acid, a potent inhibitor of dihydrofolate reductase, in rat liver slices incubated with folic acid

During investigation of folate polyglutamate biosynthesis in rat liver slices utilizing [2-(14)C]folic acid, a folate compound that behaved like a polyglutamate form in the Sephadex G-15 gel filtration system was found to accumulate. Subsequent chromatographic, spectral, chemical, and enzymic studies have indicated that the compound formed in liver slices incubated with [(14)C]folic acid with and without methotrexate was 10-formyl folate. This folate is of interest in that it is the most potent natural inhibitor of dihydrofolate reductase known and may be capable of serving a regulatory function within the cell.