formylTHFdependent

formylTHFdependent is a term used in biochemistry to describe reactions and enzymes that rely on 10-formyl-tetrahydrofolate (10-formyl-THF) as a donor of formyl groups in one-carbon metabolism. In this context, 10-formyl-THF serves as a one-carbon donor in the synthesis of purine nucleotides and other formylation reactions, linking folate metabolism to nucleotide biosynthesis.

Key examples of formylTHFdependent enzymes occur in de novo purine biosynthesis. Glycinamide ribonucleotide transformylase (GAR transformylase; PurN) transfers a formyl group from 10-formyl-THF to glycinamide ribonucleotide (GAR), yielding formylglycinamide ribonucleotide (FGAR). AICAR transformylase (the transformylase domain of PurH) formylates AICAR to FAICAR in the purine pathway. In bacteria, alternative forms exist that may use different donors, but the classically described formylTHFdependent steps specifically use 10-formyl-THF as the formyl donor. Additionally, some bacteria employ tRNA formyltransferases that use 10-formyl-THF to formylate the initiator tRNA, a related formylation reaction tied to translation initiation.

Physiological and clinical relevance stems from the essential role of these reactions in purine nucleotide biosynthesis. The availability of 10-formyl-THF links folate metabolism to cell growth and proliferation. Consequently, antifolate drugs such as methotrexate reduce the cellular pool of 10-formyl-THF, inhibiting formylTHFdependent steps and exerting antiproliferative effects. The term formylTHFdependent is used in metabolic databases and literature to categorize enzymes that directly transfer a formyl group from 10-formyl-THF to substrates.