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Fatty Acid Labeling from Glutamine in Hypoxia Can Be Explained by Isotope Exchange without Net Reductive Isocitrate Dehydrogenase (IDH) Flux

Author(s): Fan, Jing; Kamphorst, Jurre J.; Rabinowitz, Joshua D.; Shlomi, Tomer

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dc.contributor.authorFan, Jing-
dc.contributor.authorKamphorst, Jurre J.-
dc.contributor.authorRabinowitz, Joshua D.-
dc.contributor.authorShlomi, Tomer-
dc.date.accessioned2020-10-30T18:50:18Z-
dc.date.available2020-10-30T18:50:18Z-
dc.date.issued2013-10-25en_US
dc.identifier.citationFan, Jing, Kamphorst, Jurre J., Rabinowitz, Joshua D., Shlomi, Tomer. (2013). Fatty Acid Labeling from Glutamine in Hypoxia Can Be Explained by Isotope Exchange without Net Reductive Isocitrate Dehydrogenase (IDH) Flux. Journal of Biological Chemistry, 288 (43), 31363 - 31369. doi:10.1074/jbc.M113.502740en_US
dc.identifier.issn0021-9258-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr1bz31-
dc.descriptionJournal of Biological Chemistry. Volume 288, Issue 43, 25 October 2013, Pages 31363-31369.en_US
dc.description.abstractAcetyl-CoA is an important anabolic precursor for lipid biosynthesis. In the conventional view of mammalian metabolism, acetyl-CoA is primarily derived by the oxidation of glucose-derived pyruvate in mitochondria. Recent studies have employed isotope tracers to show that in cancer cells grown in hypoxia or with defective mitochondria, a major fraction of acetyl-CoA is produced via another route, reductive carboxylation of glutaminederived α-ketoglutarate (catalyzed by reverse flux through isocitrate dehydrogenase, IDH). Here, we employ a quantitative flux model to show that in hypoxia and in cells with defective mitochondria, oxidative IDH flux persists and may exceed the reductive flux. Therefore, IDH flux may not be a net contributor to acetyl-CoA production, although we cannot rule out net reductive IDH flux in some compartments. Instead of producing large amounts of net acetyl-CoA reductively, the cells adapt by reducing their demand for acetyl-CoA by importing rather than synthesizing fatty acids. Thus, fatty acid labeling from glutamine in hypoxia can be explained by spreading of label without net reductive IDH flux. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.format.extent288.43:31363 - 31369en_US
dc.language.isoen_USen_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsFinal published version. Article is made available in OAR by the publisher's permission or policy.en_US
dc.titleFatty Acid Labeling from Glutamine in Hypoxia Can Be Explained by Isotope Exchange without Net Reductive Isocitrate Dehydrogenase (IDH) Fluxen_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1074/jbc.M113.502740-
dc.date.eissued2013-09-12en_US
dc.identifier.eissn1083-351X-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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