Target intelligence / Profile preview

Folate cycle enzyme

Molecular classification
Enzyme, Transferase, Reductase
01

Overview

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].

Other names
Folate metabolism enzymesOne-carbon metabolism enzymesC1 metabolism enzymesFolate pathway enzymes
02

Mechanism of action

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

03

Biological functions

Nucleotide synthesis (DNA and RNA)Amino acid metabolism (e.g., methionine, serine, glycine, histidine)DNA methylation and gene expression regulationCell proliferationCellular differentiation
04

Disease associations

CancerCardiovascular diseaseNeural tube defects (congenital birth defects)AnemiaNeurodegenerative disease
05

Safety considerations

Bone marrow suppression (pancytopenia)Gastrointestinal toxicity (mucositis)Organ toxicity (liver, renal due to drug toxicity)Teratogenicity (in fetal development, neural tube defects with folate deficiency)
06

Interacting drugs

Methotrexate (DHFR inhibitor)

4 more in the full profile.

07

Biomarkers

Expression/activity of DHFR, SHMT2, MTHFD2, FPGS, GGH (correlate with sensitivity to antifolate drugs)Homocysteine (plasma, reflects pathway disruption)

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