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

Reductive glutamine metabolism is a function of the α-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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Veröffentlicht in:Nature Communications 2013, Vol.4, p.2236
Hauptverfasser: Fendt, Sarah-Maria, Bell, Eric L, Keibler, Mark A, Olenchock, Benjamin A, Mayers, Jared R, Wasylenko, Thomas M, Vokes, Natalie I, Guarente, Leonard, Vander Heiden, Matthew G, Stephanopoulos, Gregory
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container_title Nature Communications
container_volume 4
creator Fendt, Sarah-Maria
Bell, Eric L
Keibler, Mark A
Olenchock, Benjamin A
Mayers, Jared R
Wasylenko, Thomas M
Vokes, Natalie I
Guarente, Leonard
Vander Heiden, Matthew G
Stephanopoulos, Gregory
description 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.
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title Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
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