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Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism
Abstract
The recognition that mitochondria participate in folate-mediated one-carbon metabolism grew out of pioneering work beginning in the 1950s from the laboratories of D.M. Greenberg, C.G. Mackenzie, and G. Kikuchi. These studies revealed mitochondria as the site of oxidation of one-carbon donors such as serine, glycine, sarcosine, and dimethylglycine. Subsequent work from these laboratories and others demonstrated the participation of folate coenzymes and folate-dependent enzymes in these mitochondrial processes. Biochemical and molecular genetic approaches in the 1980s and 1990s identified many of the enzymes involved and revealed an interdependence of cytoplasmic and mitochondrial one-carbon metabolism. These studies led to the development of a model of eukaryotic one-carbon metabolism that comprises parallel cytosolic and mitochondrial pathways, connected by one-carbon donors such as serine, glycine, and formate. Sequencing of the human and other mammalian genomes has facilitated identification of the enzymes that participate in this intercompartmental one-carbon metabolism, and animal models are beginning to clarify the roles of the cytoplasmic and mitochondrial isozymes of these enzymes. Identifying the mitochondrial transporters for the one-carbon donors and elucidating how flux through these pathways is controlled are two areas ripe for exploration.
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“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 [67]
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Background
Metadata
- Authors
- Tibbetts, A. S., & Appling, D. R.
- Affiliations
- The University of Texas at Austin (US)
- ORCID
- Appling, Dean R.
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2010-07-01
- Volume
- 30
- Issue
- 1
- Pages
- 57-81
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W2145912883
- Cited by
- 692
- References
- 157
- Citations by year
- 2026: 42 · 2025: 40 · 2024: 40 · 2023: 53 · 2022: 70 · 2021: 55 · 2020: 61 · 2019: 61 · 2018: 55 · 2017: 33 · 2016: 51 · 2015: 26 · 2014: 33 · 2013: 28 · 2012: 27
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- mitochondrial metabolism, glycine oxidation, folate coenzymes, folate-dependent enzymes, serine, glycine, formate, isozymes, metabolic flux control
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Folic Acid, Humans, Mammals, Mitochondria, One-Carbon Group Transferases
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