Cited by 2,239Folate and B Vitamins ResearchEpigenetics and DNA MethylationBiochemical and Molecular Research

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One-Carbon Metabolism in Health and Disease

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Ducker, Gregory S., Rabinowitz, Joshua D.·2017·Cell Metabolism

DOI 10.1016/j.cmet.2016.08.009PMC PMC5353360

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Abstract

One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention.

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Authors: Ducker, G. S., & Rabinowitz, J. D.
Affiliations: Princeton University (US)
Corresponding author: Rabinowitz, Joshua D.
ORCID: Ducker, Gregory S.
Rabinowitz, Joshua D.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2017-01
Volume: 25
Issue: 1
Pages: 27-42
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2016.08.009
PMC: PMC5353360
OpenAlex: W2520894026
Cited by: 2,239
References: 153
Citations by year: 2026: 366 · 2025: 308 · 2024: 316 · 2023: 250 · 2022: 263 · 2021: 261 · 2020: 205 · 2019: 144 · 2018: 80 · 2017: 41
FWCI: 14.04
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Stand Up To Cancer
National Cancer Institute (R01CA163591)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK019525)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords: one-carbon metabolism, folic acid, folate pathway, purine biosynthesis, thymidine biosynthesis, amino acid homeostasis, methionine metabolism, serine metabolism, glycine metabolism, epigenetic maintenance, redox defense, NADPH production, isotope tracing, cancer metabolism, stem cells, development (biology)
MeSH terms: Animals, Carbon, Disease, Health, Humans, Mitochondria, Neoplasms, Metabolic Networks and Pathways

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