Cited by 695Folate and B Vitamins ResearchMetabolism and Genetic DisordersBiochemical and Molecular Research

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Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism

Tibbetts, Anne S., Appling, Dean R.·2010·Annual Review of Nutrition

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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 Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928
Genomewide Association Analysis of Coronary Artery Disease
Samani, N. J., Erdmann, J., Hall, A. S., Hengstenberg, C., Mangino, M., Mayer, B., Dixon, R. J., Meitinger, T., Braund, P., Wichmann, H.-E., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072366 · Cited by 2,044
Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside
Pebay‐Peyroula, E., Dahout-Gonzalez, C., Kahn, R., Trézéguet, V., Lauquin, G. J. ‐., & Brandolin, G. (2003) · Nature · doi:10.1038/nature02056 · Cited by 998
The mitochondrial transporter family (SLC25): physiological and pathological implications
Palmieri, F. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1099-7 · Cited by 764
Biochemistry of Mitochondria
Wojtczak, L., & Kaniuga, Z. (1966) · Nature · doi:10.1038/2111239a0 · Cited by 691
Chapter 1 Folate‐Mediated One‐Carbon Metabolism
Fox, J. T., & Stover, P. J. (2008) · Vitamins & Hormones · doi:10.1016/s0083-6729(08)00401-9 · Cited by 402
Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia
Kikuchi, G., Motokawa, Y., Yoshida, T., & Hiraga, K. (2008) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.84.246 · Cited by 381
GENETICS OF SOMATIC MAMMALIAN CELLS
Puck, T. T., & Fisher, H. W. (1956) · The Journal of Experimental Medicine · doi:10.1084/jem.104.3.427 · Cited by 375

Show all 157 references

Research works printed but not linked: 7

Barlowe CK, 1988, Biofactors, 1, 171
Garrow TA, 2001, Homocysteine in Health and Disease, 145
Kao FT, 1975, Genetics, 79, 343
Sheid B, 1968, Cancer Res., 28, 2512
Trippett TM, 2001, Cancer Res., 61, 1941
Veech RL, 1987, Pyridine Nucleotide Coenzymes. Chemical, Biochemical, and Medical Aspects, Part B, 79
Wang FK, 1967, Biochem. Z., 346, 458

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“[30] In the cytoplasm, MTHFD1 converts 5,10-methylene THF to 5,10-methenyl-THF, then to 10-formyl-THF and formate.”
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“MTHFD1 is a tri-functional enzyme composed of two domains ( 75 ): an N-terminal 5,10- methynyl-THF cyclohydrolase and 5,10-meTHF dehydrogenase (CD) domain, and a C-terminal 10- formyl-THF synthetase (S) domain (Fig.”
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“These folate adducts provide their one-carbon units to generate the biomolecules noted above (4).”
Background
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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
DOI: 10.1146/annurev.nutr.012809.104810
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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Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism

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