Methylenetetrahydrofolate dehydrogenase (NADP+)

In enzymology, a methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) is an enzyme that catalyzes the chemical reaction

5,10-methylenetetrahydrofolate + NADP⁺ ${\displaystyle \rightleftharpoons }$ 5,10-methenyltetrahydrofolate + NADPH + H⁺

methylenetetrahydrofolate dehydrogenase (NADP+)
Methylenetetrahydrofolate dehydrogenase dimer, Human
Identifiers
EC no.	1.5.1.5
CAS no.	9029-14-5
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

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

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

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

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).