ArticleThe Journal of biological chemistry2020
Allosteric inhibition of MTHFR prevents futile SAM cycling and maintains nucleotide pools in one-carbon metabolism.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- 5,10-Methylenetetrahydrofolate Reductase─the Key Allosteric Regulator in One-Carbon Metabolism.Biochemistry · 2026Review
- Review
- Exploratory assessment of preconception phthalate exposure on pregnancy and offspring health outcomes in mice.Journal of the Endocrine Society · 2026Article
- D-mannose blocks S-adenosylmethionine generation to suppress macrophage IL-1β expression.Frontiers in immunology · 2026Article
- High-Seas Marine Microorganism Delivers an Extract That Dampens LPS-Driven Pro-Inflammatory Signaling:Marine drugs · 2025Article
- Phospho-Switch: Regulation of the Activity of SAM-Dependent Methyltransferases UsingInternational journal of molecular sciences · 2025Article
- Article
- Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025Review
- Folate metabolism in myelofibrosis: a missing key?Annals of hematology · 2025Review
- Utilizing Flaxseed as an Antimicrobial Alternative in Chickens: Integrative Review forCurrent issues in molecular biology · 2024Review
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
- Structural basis of S-adenosylmethionine-dependent allosteric transition from active to inactive states in methylenetetrahydrofolate reductase.Nature communications · 2024Article
- The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.International journal of molecular sciences · 2024Review
- Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase.Nature communications · 2024Article
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy.NPJ precision oncology · 2023Article
- Maternal Folic Acid Supplementation Improves the Intestinal Health of Offspring Porcine by Promoting the Proliferation and Differentiation of Intestinal Stem Cells.Animals : an open access journal from MDPI · 2023Article
- Article
- Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond.Metabolites · 2022Review
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Methylenetetrahydrofolate reductase (MTHFR) links the folate cycle to the methionine cycle in one-carbon metabolism. The enzyme is known to be allosterically inhibited by SAM for decades, but the importance of this regulatory control to one-carbon metabolism has never been adequately understood. To shed light on this issue, we exchanged selected amino acid residues in a highly conserved stretch within the regulatory region of yeast MTHFR to create a series of feedback-insensitive, deregulated mutants. These were exploited to investigate the impact of defective allosteric regulation on one-carbon metabolism. We observed a strong growth defect in the presence of methionine. Biochemical and metabolite analysis revealed that both the folate and methionine cycles were affected in these mutants, as was the transsulfuration pathway, leading also to a disruption in redox homeostasis. The major consequences, however, appeared to be in the depletion of nucleotides.
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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.