biostudies-literatureHuergo LFBiotechnology and Biological Sciences Research Council419-35https://www.ebi.ac.uk/biostudies/studies/S-EPMC4651028biostudies-literatureUnknown79(4)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 patMicrobiology and molecular biology reviews : MMBRThe Emergence of 2-Oxoglutarate as a Master Regulator Metabolite.PMC4651028BBS/E/J/00000016Dixon RHuergo LFfalseThe Emergence of 2-Oxoglutarate as a Master Regulator Metabolite.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 pat2015-01-01T00:00:00Z2015 Dec2025-04-18T18:28:20.739Z2019-03-27T02:02:19ZS-EPMC46510282642471610.1128/mmbr.00038-1510.1128/MMBR.00038-15