ArticleScientific reports2019
The 5-formyltetrahydrofolate futile cycle reduces pathway stochasticity in an extended hybrid-stochastic model of folate-mediated one-carbon metabolism.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Neuroimaging in cerebral folate deficiencies.Pediatric radiology · 2026Review
- Gut microbiome derived folate metabolite suppresses colorectal cancer progression.bioRxiv : the preprint server for biology · 2026Article
- A mathematical model of folate-mediated one-carbon metabolism in Down syndrome.NPJ systems biology and applications · 2026Article
- Photorespiration is linked to DNA methylation by formate as a one-carbon source.Nature plants · 2026Article
- Maternal red blood cell folate metabolites were dynamically associated with neonatal amino acids and acylcarnitines in heel blood: a prospective cohort study.Nutrition & metabolism · 2026Article
- Integrated transcriptomic and metabolomic profiling identifiesFood chemistry. Molecular sciences · 2025Article
- 5-Formyltetrahydrofolate in a Cohort of Pregnant Women Following Folic Acid Supplementation.ACS omega · 2025Article
- Folate from probiotic bacteria and its therapeutic applications.Archives of microbiology · 2025Review
- Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets.Scientific reports · 2025Article
- Article
- 5,10-methenyltetrahydrofolate synthetase deficiency: An extreme rare defect of folate metabolism in two Dutch siblings.JIMD reports · 2024Article
- Reduced methionine synthase expression results in uracil accumulation in mitochondrial DNA and impaired oxidative capacity.PNAS nexus · 2023Article
- Integrated Network Pharmacology Analysis and Serum Metabolomics to Reveal the Anti-malaria Mechanism of Artesunate.ACS omega · 2022Article
- Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men.Frontiers in genetics · 2021Article
- A QSP model of prostate cancer immunotherapy to identify effective combination therapies.Scientific reports · 2020Article
- A case of 5,10-methenyltetrahydrofolate synthetase deficiency due to biallelic null mutations with novel findings of elevated neopterin and macrocytic anemia.Molecular genetics and metabolism reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
In folate-mediated one-carbon metabolism (FOCM), 5-formyltetrahydrofolate (5fTHF), a one-carbon substituted tetrahydrofolate (THF) vitamer, acts as an intracellular storage form of folate and as an inhibitor of the folate-dependent enzymes phosphoribosylaminoimidazolecarboxamide formyltransferase (AICARFT) and serine hydroxymethyltransferase (SHMT). Cellular levels of 5fTHF are regulated by a futile cycle comprising the enzymes SHMT and 5,10-methenyltetrahydrofolate synthetase (MTHFS). MTHFS is an essential gene in mice; however, the roles of both 5fTHF and MTHFS in mammalian FOCM remain to be fully elucidated. We present an extension of our previously published hybrid-stochastic model of FOCM by including the 5fTHF futile-cycle to explore its effect on the FOCM network. Model simulations indicate that MTHFS plays an essential role in preventing 5fTHF accumulation, which consequently averts inhibition of all other reactions in the metabolic network. Moreover, in silico experiments show that 10-formylTHF inhibition of MTHFS is critical for regulating purine synthesis. Model simulations also provide evidence that 5-methylTHF (and not 5fTHF) is the predominant physiological binder/inhibitor of SHMT. Finally, the model simulations indicate that the 5fTHF futile cycle dampens the stochastic noise in FOCM that results from both folate deficiency and a common variant in the methylenetetrahydrofolate reductase (MTHFR) gene.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.