ArticleScientific reports2017
A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the common C677T MTHFR variant on de novo thymidylate biosynthesis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A mathematical model of folate-mediated one-carbon metabolism in Down syndrome.NPJ systems biology and applications · 2026Article
- Analyzing the Efficacy and Potential Risks of Nitrous Oxide for Pain Management During Labor: A Narrative Review.Clinical pharmacology : advances and applications · 2026Review
- Medicinal chemistry perspective of pyrido[2,3-RSC advances · 2023Review
- Methionine synthase is essential for cancer cell proliferation in physiological folate environments.Nature metabolism · 2021Article
- p53 Disruption Increases Uracil Accumulation in DNA of Murine Embryonic Fibroblasts and Leads to Folic Acid-Nonresponsive Neural Tube Defects in Mice.The Journal of nutrition · 2020Article
- A QSP model of prostate cancer immunotherapy to identify effective combination therapies.Scientific reports · 2020Article
- Serine hydroxymethyltransferase controls blood-meal digestion in the midgut of Aedes aegypti mosquitoes.Parasites & vectors · 2019Article
- The MTHFR 677C>T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women.The American journal of clinical nutrition · 2019Article
- Rat liver folate metabolism can provide an independent functioning of associated metabolic pathways.Scientific reports · 2019Article
- The 5-formyltetrahydrofolate futile cycle reduces pathway stochasticity in an extended hybrid-stochastic model of folate-mediated one-carbon metabolism.Scientific reports · 2019Article
- Pro-Con Debate: Nitrous Oxide for Labor Analgesia.BioMed research international · 2019Review
- Cell cycle regulation of folate-mediated one-carbon metabolism.Wiley interdisciplinary reviews. Systems biology and medicine · 2018Review
- Nuclear Folate Metabolism.Annual review of nutrition · 2018Review
- Safety of folic acid.Annals of the New York Academy of Sciences · 2018Review
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Authors and funding
6 authors.
Funding
Abstract
Folate-mediated one-carbon metabolism (FOCM) is an interconnected network of metabolic pathways, including those required for the de novo synthesis of dTMP and purine nucleotides and for remethylation of homocysteine to methionine. Mouse models of folate-responsive neural tube defects (NTDs) indicate that impaired de novo thymidylate (dTMP) synthesis through changes in SHMT expression is causative in folate-responsive NTDs. We have created a hybrid computational model comprised of ordinary differential equations and stochastic simulation. We investigated whether the de novo dTMP synthesis pathway was sensitive to perturbations in FOCM that are known to be associated with human NTDs. This computational model shows that de novo dTMP synthesis is highly sensitive to the common MTHFR C677T polymorphism and that the effect of the polymorphism on FOCM is greater in folate deficiency. Computational simulations indicate that the MTHFR C677T polymorphism and folate deficiency interact to increase the stochastic behavior of the FOCM network, with the greatest instability observed for reactions catalyzed by serine hydroxymethyltransferase (SHMT). Furthermore, we show that de novo dTMP synthesis does not occur in the cytosol at rates sufficient for DNA replication, supporting empirical data indicating that impaired nuclear de novo dTMP synthesis results in uracil misincorporation into DNA.
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