Human Metabolome Database (HMDB): Oxoglutaric acid, also known as alpha-ketoglutarate, alpha-ketoglutaric acid, AKG or 2-Oxoglutaric acid, is classified as a gamma-keto acid or a Gamma-keto acid derivative. Gamma-keto acids are organic compounds containing an aldehyde substituted with a keto group on the C4 carbon atom. Alpha-ketoglutarate is considered to be soluble (in water) and acidic. Alpha-ketoglutarate (AKG) is a key molecule in the Krebs, TCA or citric acid cycle, playing a fundamental role in determining the overall rate of this important metabolic process (PMID: 26759695). In the TCA cycle, AKG is decarboxylated to succinyl-CoA and carbon dioxide by AKG dehydrogenase, which functions as a key control point of the TCA cycle. Additionally, AKG can be generated from isocitrate by oxidative decarboxylation catalyzed by the enzyme known as isocitrate dehydrogenase (IDH). In addition to these routes of production, AKG can be produced from glutamate by oxidative deamination via glutamate dehydrogenase, and as a product of pyridoxal phosphate-dependent transamination reactions (mediated by branched-chain amino acid transaminases) in which glutamate is a common amino donor. AKG is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. In particular, AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in skeletal muscles (PMID: 26759695). Interestingly, enteric feeding of AKG supplements can significantly increase circulating plasma levels of such hormones as insulin, growth hormone and insulin like growth factor-1 (PMID: 26759695). It has recently been shown that AKG can extend the lifespan of adult C. elegans by inhibiting ATP synthase and TOR (PMID: 24828042). In combination with molecular oxygen, alpha-ketoglutarate is required for the hydroxylation of proline to hydroxyproline in the production of Type 1 collagen. A recent study has shown that Alpha-ketoglutarate promotes TH1 differentiation along with the depletion of glutamine thereby favoring Treg (regulatory T-cell) differentiation (PMID: 26420908). Alpha-ketoglutarate has been found to be associated with fumarase deficiency, 2-Ketoglutarate dehydrogenase complex deficiency and D-2-hydroxyglutaric aciduria which is an inborn error of metabolism (PMID: 8338207).