2-Ketoglutaric acid

An intermediate in the citric acid cycle

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Background

α-Ketoglutaric acid is an α-keto acid and a rate-determining metabolic intermediate in the citric acid cycle in its conjugate base form, α-ketoglutarate.^1,2 It is formed via oxidative decarboxylation of isocitrate by isocitrate dehydrogenase (IDH), oxidative deamination of glutamate by glutamate dehydrogenase, or by pyridoxal phosphate-dependent transamination.² α-Ketoglutaric acid is decarboxylated to succinyl-CoA by α-ketoglutarate dehydrogenase, a rate limiting step in the citric acid cycle. It is a precursor of glutamine and glutamate, energy sources for enterocytes and various immune cells, and an antioxidant with roles in immune homeostasis, aging, protein synthesis, and bone development.^2,3

1.Krebs, H.A., Salvin, E., and Johnson, W.A.The formation of citric and α-ketoglutaric acids in the mammalian bodyBiochem. J.32(1)113-117(1938) 2.Wu, N., Yang, M., Gaur, U., et al.Alpha-ketoglutarate: Physiological functions and applicationsBiomol. Ther. (Seoul)24(1)1-8(2016) 3.Liu, S., He, L., and Yao, K.The antioxidative function of alpha-ketoglutarate and its applicationsBiomed. Res. Int.3408467(2018)