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

Abstract

During investigations of folate polyglutamate biosynthesis in rat liver slices utilizing [2 14C] 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 indicated that the compound formed in liver slices incubated with [14C] 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.