tetrahydrofolat

Tetrahydrofolate, commonly abbreviated THF and also referred to by the variant spelling tetrahydrofolat, is the fully reduced, biologically active form of folate. It is produced in cells by the enzymatic reduction of dihydrofolate and serves as the central coenzyme in one-carbon metabolism, carrying single-carbon units in different oxidation states for transfer to various substrates.

THF and its derivatives participate in key biosynthetic pathways. N5,N10-methylenetetrahydrofolate supplies a methylene group for thymidylate synthesis, enabling conversion of dUMP to dTMP, a step essential for DNA replication. N5-formyltetrahydrofolate and N5,N10-molybdenum forms donate carbon units in purine nucleotide biosynthesis. N5-methyltetrahydrofolate acts as a methyl donor in the methionine cycle, converting homocysteine to methionine via methionine synthase and regenerating THF for further use.

Dietary folates, found in leafy greens, legumes, and fortified foods, are absorbed and converted intracellularly to THF and its derivatives. The enzyme dihydrofolate reductase reduces dihydrofolate to THF, a prerequisite for downstream one-carbon transfers.

Clinical relevance includes the impact of THF-dependent reactions on DNA synthesis and repair. Folate deficiency can lead to megaloblastic anemia and, in pregnancy, neural tube defects. Antifolate drugs, notably methotrexate, inhibit dihydrofolate reductase, reducing THF availability and disrupting nucleotide synthesis, a mechanism exploited in cancer chemotherapy and some immunosuppressive therapies. Adequate folate intake remains important for maintaining THF-dependent metabolic processes.