Methylenetetrahydrofolate dehydrogenase (NADP+)

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methylenetetrahydrofolate dehydrogenase (NADP+)
Methylenetetrahydrofolate dehydrogenase dimer, Human
EC no.
CAS no.9029-14-5
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

In enzymology, a methylenetetrahydrofolate dehydrogenase (NADP+) (EC is an enzyme that catalyzes the chemical reaction

5,10-methylenetetrahydrofolate + NADP+ 5,10-methenyltetrahydrofolate + NADPH + H+

Thus, the two substrates of this enzyme are 5,10-methylenetetrahydrofolate and NADP+, whereas its 3 products are 5,10-methenyltetrahydrofolate, NADPH, and H+.

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.

Structural studies[edit]

As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 1A4I, 1DIA, 1DIB, 1DIG, 1LU9, 1LUA, 2C2X, and 2C2Y.

Clinical significance[edit]

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).

Alternative names[edit]

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).


  • Hatefi Y, Osborn MJ, Kay LD, Huennekins FM (1957). "Hydroxymethyl tetrahydrofolic dehydrogenase". Journal of Biological Chemistry. 227 (2): 637–47. doi:10.1016/S0021-9258(18)70744-8. PMID 13462986.
  • Osborn MJ, Huennekens FM (1957). "Participation of anhydroleucovorin in the hydroxymethyl tetrahydrofolic dehydrogenase system". Biochimica et Biophysica Acta. 26 (3): 646–7. doi:10.1016/0006-3002(57)90117-8. PMID 13499428.
  • Ramasastri BV, Blakley RL (1962). "5,10-Methylenetetrahydrofolic dehydrogenase from bakers' yeast. I Partial purification and some properties". The Journal of Biological Chemistry. 237: 1982–8. doi:10.1016/S0021-9258(19)73970-2. PMID 14490085.
  • Yeh YC, Greenberg DM (1965). "Purification and properties of N5, N10-Methylenetetra-hydrofolate dehydrogenase of calf thymus". Biochimica et Biophysica Acta (BBA) - Enzymology and Biological Oxidation. 105 (2): 279–91. doi:10.1016/s0926-6593(65)80152-7. PMID 4379024.