ArticleRedox biology2021
The toxic side of one-carbon metabolism and epigenetics.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 80 citations in OpenAlex.
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Article
- A semi-automatization magnetic solid-phase extraction method of LC-MS/MS for the quantification of homocysteine and its related metabolites in serum.Practical laboratory medicine · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Liver-muscle metabolic crosstalk: xanthosine as a key effector of broiler myogenesis.Journal of animal science and biotechnology · 2026Article
- Hypoxia facilitates triple-negative breast cancer stem cells enrichment and stemness maintenance through oxidized ataxia telangiectasia mutated-induced one-carbon metabolism.World journal of stem cells · 2026Article
- Integrated metabolomics and machine learning identify predictive biomarkers via SHAP analysis for sintilimab-induced rash in lung cancer patients.Frontiers in pharmacology · 2026Article
- Formate Reduces Ischemic Injury in Female Hearts Lacking Alcohol Dehydrogenase 5.FASEB bioAdvances · 2025Article
- Translesion polymerases and DNA-protein crosslink repair shapes the cellular response to formaldehyde-induced DNA damage in ssDNA.Nucleic acids research · 2025Article
- Examination of Genetic and Epigenetic Characteristics of Patients with Hyperhomocysteinemia Following High-Dose Folic Acid Consumption.Nutrients · 2025Article
- Homocysteine and risk of interstitial lung disease: A mendelian randomization approach to causal inference.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2025Article
- Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State.International journal of molecular sciences · 2025Review
- Effect of gentiopicroside on endogenous formaldehyde homocysteine-pathway related proteins in rats with non-alcoholic steatohepatitis.Frontiers in pharmacology · 2025Article
- METTL16 suppresses ferroptosis in cholangiocarcinoma by promoting ATF4 via mInternational journal of biological sciences · 2025Article
- Distinct DNA repair mechanisms prevent formaldehyde toxicity during development, reproduction and aging.Nucleic acids research · 2024Article
- Propionic Acidemia, Methylmalonic Acidemia, and Cobalamin C Deficiency: Comparison of Untargeted Metabolomic Profiles.Metabolites · 2024Article
- Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy.Acta pharmaceutica Sinica. B · 2024Article
- A mitochondrial-targeted activity-based sensing probe for ratiometric imaging of formaldehyde reveals key regulators of the mitochondrial one-carbon pool.Chemical science · 2024Article
- Isolation and detection of DNA-protein crosslinks in mammalian cells.Nucleic acids research · 2024Article
- Interaction Between the PERK/ATF4 Branch of the Endoplasmic Reticulum Stress and Mitochondrial One-Carbon Metabolism Regulates Neuronal Survival After Intracerebral Hemorrhage.International journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One-carbon metabolism is a central metabolic hub that provides one-carbon units for essential biosynthetic reactions and for writing epigenetics marks. The leading role in this hub is performed by the one-carbon carrier tetrahydrofolate (THF), which accepts formaldehyde usually from serine generating one-carbon THF intermediates in a set of reactions known as the folate or one-carbon cycle. THF derivatives can feed one-carbon units into purine and thymidine synthesis, and into the methionine cycle that produces the universal methyl-donor S-adenosylmethionine (AdoMet). AdoMet delivers methyl groups for epigenetic methylations and it is metabolized to homocysteine (Hcy), which can enter the transsulfuration pathway for the production of cysteine and lastly glutathione (GSH), the main cellular antioxidant. This vital role of THF comes to an expense. THF and other folate derivatives are susceptible to oxidative breakdown releasing formaldehyde, which can damage DNA -a consequence prevented by the Fanconi Anaemia DNA repair pathway. Epigenetic demethylations catalysed by lysine-specific demethylases (LSD) and Jumonji histone demethylases can also release formaldehyde, constituting a potential threat for genome integrity. In mammals, the toxicity of formaldehyde is limited by a metabolic route centred on the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which oxidizes formaldehyde conjugated to GSH, lastly generating formate. Remarkably, this formate can be a significant source of one-carbon units, thus defining a formaldehyde cycle that likely restricts the toxicity of one-carbon metabolism and epigenetic demethylations. This work describes recent advances in one-carbon metabolism and epigenetics, focusing on the steps that involve formaldehyde flux and that might lead to cytotoxicity affecting human health.
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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.