Enzyme in folate metabolism

"Enzyme in folate metabolism" is not a single molecule but refers to a set of enzymes catalyzing various steps in the folate (one-carbon) pathway. Key enzymes include dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT1/SHMT2), methionine synthase, and others[3][4][6]. These enzymes are essential for transferring one-carbon units required for nucleotide (purine and thymidylate) synthesis, homocysteine remethylation to methionine, and S-adenosylmethionine (SAM) production for methylation reactions. Folate-dependent enzymes play prominent roles in DNA synthesis and repair, cell division, and epigenetic regulation via DNA and protein methylation[3][4][6]. Aberrant folate metabolism is implicated in cancer (as a chemotherapy target), cardiovascular disease (via homocysteine), developmental defects (e.g., neural tube defects), and certain anemias. Multiple drugs, especially antifolates like methotrexate, pemetrexed, and raltitrexed, target these enzymes—primarily DHFR or thymidylate synthase—to inhibit tumor growth, often balanced by leucovorin "rescue" to spare normal cells[2][3][6]. Polymorphisms in enzymes such as MTHFR may impact efficacy, toxicity, or disease risk[6].

Other names

Folate pathway enzymeFolate cycle enzymeEnzyme of folic acid metabolism

- Inhibition of dihydrofolate reductase (DHFR) (by methotrexate and related agents) to prevent the regeneration of tetrahydrofolate, thus inhibiting DNA synthesis[2][3][6]. - Inhibition of thymidylate synthase (by raltitrexed and others) to block thymidine nucleotide synthesis[2][3]. - Rescue of normal cells with folinic acid/leucovorin to bypass antifolate toxicity[2].