In enzymology, methylenetetrahydrofolate dehydrogenase (NAD<sup>+</sup>) () is an enzyme that catalyzes the chemical reaction.
The two substrates of this enzyme are 5,10-methylenetetrahydrofolate and oxidised nicotinamide adenine dinucleotide (NAD<sup>+</sup>). Its products are 5,10-methenyltetrahydrofolate, reduced NADH, and a proton.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD<sup>+</sup> or NADP<sup>+</sup> as acceptor. The systematic name of this enzyme class is 5,10-methylenetetrahydrofolate:NAD<sup>+</sup> oxidoreductase. This enzyme is also called methylenetetrahydrofolate dehydrogenase (NAD<sup>+</sup>). This enzyme participates in one carbon pool by folate.
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes and .