One-Carbon Metabolism in Health and Disease.

TitleOne-Carbon Metabolism in Health and Disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsDucker, GS, Rabinowitz, JD
JournalCell Metab
Volume25
Issue1
Pagination27-42
Date Published2017 01 10
ISSN1932-7420
KeywordsAnimals, Carbon, Disease, Health, Humans, Metabolic Networks and Pathways, Mitochondria, Neoplasms
Abstract

<p>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.</p>

DOI10.1016/j.cmet.2016.08.009
Alternate JournalCell Metab.
PubMed ID27641100
PubMed Central IDPMC5353360
Grant ListP30 DK019525 / DK / NIDDK NIH HHS / United States
R01 CA163591 / CA / NCI NIH HHS / United States