title: The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite.
abstract: 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.
authors.affiliation: 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.
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Huergo
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom ray.dixon@jic.ac.uk.
authors.forename: Ray
authors.initials: R
authors.lastname: Dixon
mesh_terms: D001105:Archaea / Q000235:genetics / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D002952:Citric Acid Cycle; D000458:Cyanobacteria / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009584:Nitrogen / Q000378:metabolism; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D007656:Ketoglutaric Acids; D014157:Transcription Factors; D002244:Carbon; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D009584:Nitrogen