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Chapter 1 Folate‐Mediated One‐Carbon Metabolism
Abstract
Tetrahydrofolate (THF) polyglutamates are a family of cofactors that carry and chemically activate one-carbon units for biosynthesis. THF-mediated one-carbon metabolism is a metabolic network of interdependent biosynthetic pathways that is compartmentalized in the cytoplasm, mitochondria, and nucleus. One-carbon metabolism in the cytoplasm is required for the synthesis of purines and thymidylate and the remethylation of homocysteine to methionine. One-carbon metabolism in the mitochondria is required for the synthesis of formylated methionyl-tRNA; the catabolism of choline, purines, and histidine; and the interconversion of serine and glycine. Mitochondria are also the primary source of one-carbon units for cytoplasmic metabolism. Increasing evidence indicates that folate-dependent de novo thymidylate biosynthesis occurs in the nucleus of certain cell types. Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies, yet the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be established. This chapter focuses on our current understanding of mammalian folate-mediated one-carbon metabolism, its cellular compartmentation, and knowledge gaps that limit our understanding of one-carbon metabolism and its regulation.
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“Folate is a crucial constituent of one‐carbon metabolism (OCM) and is important for biosynthesis of purines and thymidylate, and remethylation of homocysteine to methionine (Fox & Stover, 2008; Li, Vijayanathan, Gulinello, & Cole, 2010).”
From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Fox & Stover, 2008
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“Since MTX is delivered through all phases of ALL treatment, folate metabolism may be altered for an extended period, possibly resulting in build‐up of homocysteine (Fox & Stover, 2008; Krull et al., 2016; Li et al., 2010; Steinfeld et al., 2009), and/or secondary metabolic alterations (van der Plas et al., 2015; Steinfeld et al., 2009; Strain et al., 2013).”
From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Fox & Stover, 2008
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Meredith, M., MacNeil, A. H., Trasler, J. M., & Baltz, J. M. (2016) · Biology of Reproduction · doi:10.1095/biolreprod.115.137687 · Cited by 19
Agrawal, A., Khan, M. J., Graugnard, D. E., Vailati-Riboni, M., Rodriguez‐Zas, S. L., Osorio, J. S., & Loor, J. J. (2017) · Bioinformatics and Biology Insights · doi:10.1177/1177932217704667 · Cited by 19
Mistry, R. K., & Brewer, A. C. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7224 · Cited by 19
Armstrong, N. D., Chen, W., Brewer, M. S., Williams, S. R., Sale, M. M., Worrall, B. B., & Keene, K. L. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00358 · Cited by 19
Convergent pathways to biosynthesis of the versatile cofactor F420
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Folate Metabolism in Hepatocellular Carcinoma. What Do We Know So Far?
Quevedo-Ocampo, J., Escobedo-Calvario, A., Souza-Arroyo, V., Miranda-Labra, R. U., Bucio-Ortiz, L., Gutiérrez-Ruíz, M., Chávez-Rodríguez, L., & Gómez-Quiroz, L. (2022) · Technology in Cancer Research and Treatment · doi:10.1177/15330338221144446 · Cited by 17
Orally Administered Melatonin Prevents Lipopolysaccharide-Induced Neural Tube Defects in Mice
Fu, L., Yu, Z., Chen, Y., Xia, M., Wang, H., Zhang, C., Tao, F., & Xu, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113763 · Cited by 18
Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults
Bae, S., Kamynina, E., Farinola, A. F., Caudill, M. A., Stover, P. J., Cassano, P. A., Berry, R. J., & Peña‐Rosas, J. P. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012649 · Cited by 17
Self-citationTDCIPP exposure affects Artemia franciscana growth and osmoregulation
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DNA methylation is correlated with gene expression during early pregnancy in Bos taurus
Walker, C. G., Littlejohn, M. D., Meier, S., Roche, J. R., & Mitchell, M. D. (2013) · Physiological Genomics · doi:10.1152/physiolgenomics.00145.2012 · Cited by 18
Absence of Association Between Serum Folate and Preeclampsia in Women Exposed to Food Fortification
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Botté, E. S., Bennett, H. M., Engelberts, J. P., Thomas, T., Bell, J. J., Webster, N. S., & Luter, H. M. (2023) · ISME Communications · doi:10.1038/s43705-023-00247-3 · Cited by 17
Mitochondrial One-Carbon Metabolism and Alzheimer’s Disease
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Folate dose and form during pregnancy may program maternal and fetal health and disease risk
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Metadata
- Authors
- Fox, J. T., & Stover, P. J.
- Affiliations
- Cornell University (US)
- Venue
- Vitamins & Hormones
- Publisher
- Elsevier
- Published
- 2008
- Volume
- 79
- Pages
- 1-44
- ISSN
- 0083-6729 (ISSN-L)
- OpenAlex
- W3975443
- Cited by
- 402
- References
- 269
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 22 · 2023: 17 · 2022: 20 · 2021: 25 · 2020: 25 · 2019: 34 · 2018: 25 · 2017: 36 · 2016: 35 · 2015: 16 · 2014: 16 · 2013: 26 · 2012: 18
- FWCI
- 62.82
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Vitamins and hormones (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK58144)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- folic acid, one-carbon metabolism, thymidylate synthesis, purine biosynthesis, homocysteine remethylation, methionine biosynthesis, histidine catabolism, mitochondrial metabolism, folate deficiency, developmental anomalies
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Folic Acid, Mammals, Mitochondria, One-Carbon Group Transferases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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