Folate pathway enzymes

Folate pathway enzymes are a group of enzymes involved in folate metabolism that maintain intracellular folate homeostasis and mediate one-carbon transfer reactions essential for DNA synthesis and methylation. Key enzymes in this pathway include folylpolyglutamate synthase (FPGS), which catalyzes polyglutamylation of folate to retain it within cells; γ-glutamyl hydrolase (GGH), which hydrolyzes polyglutamylated folate into monoglutamylated folate for cellular export; dihydrofolate reductase, which reduces folic acid to tetrahydrofolate (THF); serine hydroxymethyltransferase (SHMT), which adds a one-carbon methyl group to THF; methylenetetrahydrofolate dehydrogenase (MTHFD2), which oxidizes 5,10-methylenetetrahydrofolate; and formate-tetrahydrofolate ligase, which adds a one-carbon unit to THF. These enzymes work synergistically to maintain proper folate levels for optimal cellular function and are critical for DNA synthesis, methylation, and amino acid metabolism. Dysregulation of these enzymes can affect chemosensitivity to antifolates and other chemotherapeutic agents, and has implications in various diseases including cancer[1][3].

Other names

Folate metabolism enzymesFolate-dependent enzymesOne-carbon metabolism enzymes

Inhibition of folate-dependent enzymes, Disruption of intracellular folate homeostasis, Interference with DNA synthesis and methylation