2-Ketoglutaric acid Sodium (AKG) is a key molecule in the TCA cycle. It 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. It has recently been shown that AKG can extend the lifespan of adult C. elegans by inhibiting ATP synthase and TOR. In combination with molecular oxygen, alpha-ketoglutarate is required for the hydroxylation of proline to hydroxyproline in the production of type I collagen. A recent study has shown that alpha-ketoglutarate promotes TH1 differentiation along with the depletion of glutamine thereby favouring Treg (regulatory T-cell) differentiation.