Reductive glutamine metabolism is a function of the [alpha]-ketoglutarate to citrate ratio in cells

Reductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ket...

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Bibliographic Details
Published inNature communications Vol. 4; p. 2236
Main Authors Fendt, Sarah-maria, Bell, Eric L, Keibler, Mark A, Olenchock, Benjamin A, Mayers, Jared R, Wasylenko, Thomas M, Vokes, Natalie I, Guarente, Leonard, Heiden, Matthew G Vander, Stephanopoulos, Gregory
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 01.07.2013
Subjects
Cancer
Carbon
Cell growth
Fatty acids
Hypoxia
Kinases
Medical research
Metabolism
Metabolites
Respiration
United States > US
Massachusetts
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Summary:Reductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ketoglutarate/citrate ratio is changed due to an altered acetyl-CoA to citrate conversion, and demonstrate that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio. Thus, targeting reductive glutamine conversion for a therapeutic benefit might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling, which only indirectly affects the process.
ISSN:2041-1723
DOI:10.1038/ncomms3236