Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2)

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional mitochondrial enzyme that plays a central role in folate-mediated one-carbon metabolism. It catalyzes the sequential conversion of 5,10-methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate and then to 10-formyl-tetrahydrofolate, utilizing NADP+ or NAD+ as electron acceptors. MTHFD2 is highly upregulated in various cancers and supports rapid cell proliferation by supplying nucleotides and contributing to redox homeostasis. It is also involved in DNA repair and cell morphology/motility. MTHFD2 is considered an attractive target for anti-cancer therapy, and inhibitors targeting its catalytic mechanism are being explored as potential anti-cancer agents.

Other names

NMDMCmethenyltetrahydrofolate cyclohydrolase

Inhibition of MTHFD2 catalytic activity