In enzymology, a methylenetetrahydrofolate dehydrogenase (NADP+) () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 5,10-methylenetetrahydrofolate and NADP<sup>+</sup>, whereas its 3 products are 5,10-methenyltetrahydrofolate, NADPH, and H<sup>+</sup>.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. This enzyme participates in glyoxylate and dicarboxylate metabolism and one carbon pool by folate.
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , and .
Mutations of the MTHFD1 gene may disrupt the activity of the enzyme and cause methylenetetrahydrofolate dehydrogenase 1 deficiency, also known as combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH).
The systematic name of this enzyme class is 5,10-methylenetetrahydrofolate:NADP+ oxidoreductase. Other names in common use include N5,N10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate:NADP oxidoreductase, 5,10-methylenetetrahydrofolate dehydrogenase, methylenetetrahydrofolate dehydrogenase, and methylenetetrahydrofolate dehydrogenase (NADP).