Flavin requirement and partial separation of enzymes catalysing the reduction of folic acid to tetrahydrofolic acid in liver

Abstract

A soluble enzyme system which reduces folic acid to tetra-hydrofolic acid has been extracted from acetone-dried sheep liver. The component that reduces folic acid to dihydrofolic acid has been partially separated from that which reduces dihydrofolic acid to tetra-hydrofolic acid The step that converts folic acid into dihydrofolic acid is mediated by a flavin enzyme in which either FMN or FAD can function as the active moiety. Aminopterin preferentially inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. It is concluded that the conversion of folic acid into tetrahydrofolic acid is brought about by a 2-step reduction, in which dihydrofolic acid is an intermediate, and that each step is catalysed by a distinct enzyme.