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Folate cycle enzymes are a group of enzymes involved in the intracellular metabolism of folate, mediating one-carbon transfer reactions required for the synthesis of nucleotides, methylation of DNA, RNA, and proteins, and amino acid metabolism[1][2][4][6][7]. Principal members include dihydrofolate reductase (DHFR), serine hydroxymethyltransferase (SHMT1, SHMT2), methylenetetrahydrofolate dehydrogenases (MTHFD1, MTHFD2), and folylpolyglutamate synthase (FPGS)[2][3][6]. These enzymes are essential for cellular proliferation and differentiation, and their dysregulation or inhibition is associated with cancer, anemia, cardiovascular disease, and neural tube defects[4][7][1]. Several antifolate drugs target these enzymes, notably in cancer chemotherapy and anti-infective therapy; biomarker assays (such as DHFR expression) are sometimes used to predict therapy response or toxicity[4][5][2].
Enzyme inhibition (antifolates/chemotherapy block DNA synthesis by inhibiting DHFR, thymidylate synthase, etc.); Rescuing folate pathway (folinic acid); Interfering with DNA methylation and gene expression
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