Tetrahydrofolate pathway (THF pathway)

The Tetrahydrofolate pathway, also known as folate-mediated one-carbon metabolism, describes a set of interconnected metabolic reactions in which tetrahydrofolate (THF), a reduced form of folate (vitamin B9), serves as a carrier of one-carbon units. These reactions are essential for DNA and RNA synthesis, amino acid interconversions, and methylation reactions critical for cellular function and epigenetic regulation. Disruption of this pathway is associated with megaloblastic anemia, developmental defects, and malignancy. Drugs targeting specific enzymes within this pathway—such as dihydrofolate reductase and thymidylate synthase—are widely used in cancer chemotherapy and certain infectious diseases.

Other names

folate pathwayfolate-mediated one-carbon metabolismone-carbon metabolism pathway

Inhibition of folate pathway enzymes (e.g., dihydrofolate reductase inhibitors block THF regeneration, leading to impaired DNA synthesis); Antimetabolite activity (structural mimics interfere with nucleotide biosynthesis)