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Reductive glutamine metabolism is a function of the ?-ketoglutarate to citrate ratio in cells.

ABSTRACT: 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 ?-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 ?-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.

SUBMITTER: Fendt SM

PROVIDER: S-EPMC3934748 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells.

Fendt Sarah-Maria SM Bell Eric L EL Keibler Mark A MA Olenchock Benjamin A BA Mayers Jared R JR Wasylenko Thomas M TM Vokes Natalie I NI Guarente Leonard L Vander Heiden Matthew G MG Stephanopoulos Gregory G

Nature communications 20130101

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 ...[more]

PMID: 23900562

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