ketoglutarate

Ketoglutarate most commonly refers to alpha-ketoglutarate (α-KG), or its salts such as calcium α-KG, magnesium α-KG, and potassium α-KG. It is a five-carbon dicarboxylic α-keto acid that participates in central metabolism and amino acid turnover. In cells, α-KG is an intermediate of the citric acid cycle, formed from isocitrate and subsequently converted to succinyl-CoA by the α-ketoglutarate dehydrogenase complex, with production of NADH and release of CO2. It can also be generated from glutamate through transamination, linking carbon and nitrogen metabolism.

In metabolism, α-KG acts as a key amino group acceptor, transferring amino groups to form glutamate and other amino acids. This makes it important for nitrogen transport and the regulation of amino acid pools. It also serves as an anaplerotic substrate to replenish TCA cycle intermediates during periods of high flux or metabolic stress.

Beyond energy metabolism, α-KG is a cofactor for 2-oxoglutarate–dependent dioxygenases, including prolyl hydroxylases that regulate hypoxia-inducible factor and TET enzymes involved in DNA demethylation. Through these roles, α-KG can influence epigenetic regulation and cellular responses to nutrients and oxygen.

Industrial and clinical use centers on dietary supplements presented as calcium, magnesium, or potassium α-KG. Claims about kidney support, wound healing, or athletic performance have mixed or limited evidence. Potential adverse effects include gastrointestinal upset and electrolyte disturbances, particularly with potassium salts; individuals with kidney disease or those taking certain medications should use caution. Production methods include fermentation and chemical synthesis; α-KG is also produced endogenously in metabolism.