Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2)

Methylenetetrahydrofolate dehydrogenases requiring either NADP or NAD as cofactor are involved in the interconversion of methylene, methenyl, and formyl derivatives of tetrahydrofolate. In mammals and yeast, the NADP-dependent methylenetetrahydrofolate dehydrogenase, associated with methenyltetrahydrofolate cyclohydrolase in the N-terminal domain, is fused to a formyltetrahydrofolate synthetase domain, forming a trifunctional enzyme. MTHFD2 is a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. MTHFD2 is unique in its absolute requirement for magnesium and inorganic phosphate. Both ions affect the affinity of the enzyme for NAD and have no effect on the binding of methylenetetrahydrofolate.