Tetrahydrofolate formation

Tetrahydrofolate formation refers to the enzymatic conversion processes that generate tetrahydrofolic acid from its precursors. In humans, this primarily involves the reduction of dihydrofolic acid by the enzyme dihydrofolate reductase—a step targeted by several chemotherapeutics and antibiotics. Tetrahydrofloiate acts as a carrier for single-carbon units required in critical biosynthetic pathways including purine and thymidine nucleotide production for DNA/RNA synthesis and certain amino acids. Disruption or inhibition of this pathway leads to impaired cell division and can result in clinical conditions such as megaloblastic anemia or serve as an effective strategy against rapidly dividing cells in cancer or bacteria lacking exogenous folates.

Other names

Tetrahydrofolate biosynthesisTHF synthesisTetrahydrofolic acid formation

For drugs targeting this process: Inhibition of dihydrofolate reductase by methotrexate, trimethoprim, pyrimethamine blocks reduction of dihydrofolic acid to tetrahydrofolic acid. Inhibition of dihydropteroate synthetase by sulfonamides blocks folic acid precursor synthesis in bacteria. Result: Depletion of THF impairs DNA/RNA/protein synthesis.