Folate-dependent enzyme involved in DNA synthesis

Folate-dependent enzymes involved in DNA synthesis are a group of metabolic enzymes that require folates as cofactors for the transfer of one-carbon units during critical cellular processes. These include the de novo biosynthesis of thymidylate and purines—essential steps for accurate DNA replication and repair. Key members include thymidylate synthase (TYMS), dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase (SHMT). These enzymes form multienzyme complexes that localize to the nucleus during S phase to support rapid cell division. Their activity is essential for maintaining genomic stability; deficiencies or polymorphisms can lead to increased cancer risk or other diseases. Several chemotherapeutic agents target these enzymes by inhibiting their function, thereby blocking tumor cell proliferation through disruption of nucleotide production required for DNA synthesis and methylation reactions critical for gene regulation[1][3][4].

Other names

Folate metabolism enzymesEnzymes of folate pathwayThymidylate synthase (TYMS)Dihydrofolate reductase (DHFR)Methylenetetrahydrofolate reductase (MTHFR)Serine hydroxymethyltransferase (SHMT)

Inhibition of nucleotide biosynthesis by blocking folate-dependent enzymatic activity[4]; Disruption of thymidylate and purine synthesis leading to impaired DNA replication and cell death[1][3][4]