Folate-metabolizing enzyme

Folate-metabolizing enzymes are a class of enzymes that mediate the activation, transformation, and utilization of folate (vitamin B9) derivatives in cellular metabolism. Their central roles include facilitating one-carbon transfers that are essential for the synthesis of nucleic acids (DNA, RNA), amino acids, epigenetic methylation, and other methyl group transfers. Critical enzymes in this pathway include dihydrofolate reductase (DHFR), which reduces folic acid to dihydrofolate then to tetrahydrofolate (THF); methylenetetrahydrofolate dehydrogenase (MTHFD1/2), which interconverts folate derivatives; serine hydroxymethyltransferase (SHMT), which provides one-carbon units; methionine synthase, which remethylates homocysteine to methionine using methyl-THF; and folylpolyglutamate synthetase, which generates folate polyglutamates required for intracellular retention and activity. These enzymes are targets of antifolate drugs used in cancer and infectious disease, and their dysfunction or inhibition can contribute to a wide array of diseases, from megaloblastic anemia to cancer and neurodevelopmental disorders.

Other names

Folate metabolism enzymesfolate cycle enzymesone-carbon metabolism enzymes

Enzyme inhibition (e.g., methotrexate inhibits dihydrofolate reductase); Antimetabolite interference with nucleotide biosynthesis; Enzyme rescue (supplemental folinic acid)