title: One-Carbon Metabolism in Health and Disease.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Ducker
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. Electronic address: joshr@princeton.edu.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism*; D004194:Disease; D006262:Health; D006801:Humans; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy
chemical_list: D002244:Carbon
keywords: MTHFD2; cancer metabolism; folate; mitochondria; neural tube defects; one-carbon metabolism; serine