Ketoglutarat

Ketoglutarate, also known as alpha-ketoglutarate (α-KG) or 2-oxoglutarate, is a five-carbon dicarboxylic acid that serves as a central metabolite in cellular energy and nitrogen metabolism. In the mitochondrion, α-ketoglutarate is a key intermediate of the citric acid cycle, formed from isocitrate and subsequently converted to succinyl-CoA with the release of CO2 and the production of NADH. It also links carbon and nitrogen metabolism through transamination reactions that generate glutamate.

Beyond its role in energy production, α-ketoglutarate participates in numerous biosynthetic and regulatory pathways. It accepts amino groups in transamination reactions, acting as a hub for amino acid metabolism. A broad class of enzymes, the 2-oxoglutarate-dependent dioxygenases, use α-ketoglutarate as a co-substrate. These enzymes participate in collagen synthesis via prolyl hydroxylases, and in epigenetic regulation through DNA and histone demethylation (TET and JmjC domain-containing enzymes). Their activity is influenced by cellular levels of α-ketoglutarate as well as by the related metabolites succinate and fumarate, which can act as inhibitors.

Physiologically, α-ketoglutarate is produced from glutamate or from isocitrate and serves as a crossroads between carbon and nitrogen metabolism. Dysregulation of α-ketoglutarate–dependent pathways can be associated with metabolic disturbances and altered epigenetic states in certain contexts.

In nutrition and medicine, α-ketoglutarate is marketed as a dietary supplement for athletes, aging, and gut health, but robust clinical evidence for these claims is limited. It is generally considered safe at standard dietary intakes, with adverse effects mainly reported at high doses.