10formylTHF

10-formyl-THF, or N10-formyl-tetrahydrofolate, is a derivative of tetrahydrofolate that carries a formyl group at the N10 position. It functions as a one-carbon donor in key cellular reactions and is part of the folate-mediated one-carbon metabolism pool. In cells, folate derivatives exist in polyglutamated forms that facilitate intracellular retention and transfer of one-carbon units.

Biological role and metabolism

10-formyl-THF serves as a donor of one-carbon units in purine nucleotide biosynthesis. In this pathway, GAR transformylase transfers the formyl group from 10-formyl-THF to glycinamide ribonucleotide (GAR) to form formylglycinamide ribonucleotide (FGAR), and AICAR transformylase transfers it to aminoimidazole carboxamide ribonucleotide (AICAR) to form formylaminoimidazole carboxamide ribonucleotide (FAICAR), ultimately contributing to inosine monophosphate (IMP) synthesis. In bacteria, 10-formyl-THF also provides the formyl group needed to initiate protein synthesis on formylmethionyl-tRNA, a step essential for the maturation of the bacterial initiator tRNA. The folate cycle interconverts various one-carbon carriers, including 10-formyl-THF, enabling coordinated regulation of nucleotide and amino acid metabolism.

Clinical and pharmacological context

Because 10-formyl-THF is tied to purine synthesis, its availability is affected by folate metabolism. Inhibitors of folate pathways, such as antifolates that limit THF regeneration, reduce the pool of activated one-carbon units and impair DNA synthesis. This underlies the mechanism of action for several anticancer and antimicrobial agents that target folate metabolism and one-carbon transfer reactions.

See also

Tetrahydrofolate; one-carbon metabolism; purine biosynthesis; formyltransferases.