The DOI matches its Crossref record; 154 of the 154 references it cites were found in a registry or an index.
One-Carbon Metabolism in Health and Disease
Open accessAbstract
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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“formate triggered an upregulation of differentially expressed genes (DEGs) involved in 1C metabolism, such as serine hydroxymethyltransferase 2 (Shmt2)42,58 and cystathionine gamma-lyase (Cth)59, as well as genes regulated by Nrf2 (e.g.: Cth60, NADH dehydrogenase 4 (mt-Nd4)61 and transketolase (Tkt)62,63) (Figure 6L and Table S3).”
From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [42]
In the citing paper
“The co-factor tetrahydrofolate (THF) is the carrier that mediates 1C transfer reactions for de novo nucleotide synthesis.66,67”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [66]
In the citing paper
“Mitochondrial contributions to this pathway are critical, as mitochondrial formate is the main carbon source for cytosolic 1C metabolism 66”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [66]
In the citing paper
“Increasing the intensity of anabolism requires the coordinated up-regulation of a number of biosynthetic processes, for which glycolysis and one-carbon metabolism are crucial sources of structural units [37,45,46].”
From 20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells (2024) · cites this paper as [46]
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Cites
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citationMetabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Sreekumar, A., Poisson, L., Rajendiran, T. M., Khan, A. P., Cao, Q., Yu, J., Laxman, B., Mehra, R., Lonigro, R. J., Li, Y., et al. (2009) · Nature · doi:10.1038/nature07762 · Cited by 2,269
Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis
Wald, D. S., Law, M., & Morris, J. K. (2002) · BMJ · doi:10.1136/bmj.325.7374.1202 · Cited by 1,945
Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease
(2006) · New England Journal of Medicine · doi:10.1056/nejmoa060900 · Cited by 1,729 · cited 1×
“…lowering homocysteine levels, folate and cobalamin supplementation do not reduce the incidence of cardiovascular events in the general population, arguing against high homocysteine levels directly causing cardiovascular disease (Bazzano et al., 2006; Lonn et al., 2006; Zhou et al., 2011).”
BackgroundSerine, glycine and one-carbon units: cancer metabolism in full circle
Locasale, J. W. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3557 · Cited by 1,727
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683
Methionine metabolism in mammals
Finkelstein, J. D. (1990) · The Journal of Nutritional Biochemistry · doi:10.1016/0955-2863(90)90070-2 · Cited by 1,495
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403
Birsoy, K., Wang, T., Chen, W. W., Freinkman, E., Abu-Remaileh, M., & Sabatini, D. M. (2015) · Cell · doi:10.1016/j.cell.2015.07.016 · Cited by 1,388
The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer
Kansanen, E., Kuosmanen, S. M., Leinonen, H., & Levonen, A.-L. (2013) · Redox Biology · doi:10.1016/j.redox.2012.10.001 · Cited by 1,313
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Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654
The multifaceted contributions of mitochondria to cellular metabolism
Spinelli, J. B., & Haigis, M. C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0124-1 · Cited by 1,935
Gut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398
Targeting cancer metabolism in the era of precision oncology
Stine, Z. E., Schug, Z. T., Salvino, J. M., & Dang, C. V. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00339-6 · Cited by 1,189
Metabolic regulation of cell growth and proliferation
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Metadata
- Authors
- Ducker, G. S., & Rabinowitz, J. D.
- Affiliations
- Princeton University (US)
- Corresponding author
- Rabinowitz, Joshua D.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 25
- Issue
- 1
- Pages
- 27-42
- ISSN
- 1550-4131 (ISSN-L)
- 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
- 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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