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Microbiol Mol Biol Rev. 2015 Dec;79(4):419-35. doi: 10.1128/MMBR.00038-15.

The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite.

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Instituto Nacional de Ciência e Tecnologia da Fixação Biológica de Nitrogênio, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR, Brazil Setor Litoral, Universidade Federal do Paraná, Matinhos, PR, Brazil.
Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom


The metabolite 2-oxoglutarate (also known as α-ketoglutarate, 2-ketoglutaric acid, or oxoglutaric acid) lies at the intersection between the carbon and nitrogen metabolic pathways. This compound is a key intermediate of one of the most fundamental biochemical pathways in carbon metabolism, the tricarboxylic acid (TCA) cycle. In addition, 2-oxoglutarate also acts as the major carbon skeleton for nitrogen-assimilatory reactions. Experimental data support the conclusion that intracellular levels of 2-oxoglutarate fluctuate according to nitrogen and carbon availability. This review summarizes how nature has capitalized on the ability of 2-oxoglutarate to reflect cellular nutritional status through evolution of a variety of 2-oxoglutarate-sensing regulatory proteins. The number of metabolic pathways known to be regulated by 2-oxoglutarate levels has increased significantly in recent years. The signaling properties of 2-oxoglutarate are highlighted by the fact that this metabolite regulates the synthesis of the well-established master signaling molecule, cyclic AMP (cAMP), in Escherichia coli.

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