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

被引：290

作者：

Fendt, Sarah-Maria ^{[1
]}

Bell, Eric L. ^{[2
]}

Keibler, Mark A. ^{[1
]}

Olenchock, Benjamin A. ^{[3
,4
,5
]}

Mayers, Jared R. ^{[2
,3
]}

Wasylenko, Thomas M. ^{[1
]}

Vokes, Natalie I. ^{[3
]}

Guarente, Leonard ^{[2
]}

Vander Heiden, Matthew G. ^{[2
,3
,5
]}

Stephanopoulos, Gregory ^{[1
]}

机构：

[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Koch Inst Canc Res, Cambridge, MA 02139 USA

[4] Brigham & Womens Hosp, Boston, MA 02115 USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

PYRUVATE-DEHYDROGENASE; FLUX; CARBOXYLATION; ADAPTATION; HYPOXIA; KINASE; GROWTH;

D O I：

10.1038/ncomms3236

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 alpha-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 alpha-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.

引用

页数：11

共 38 条

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