alpha-Ketoglutaric acid

α-Ketoglutaric acid (2-oxoglutaric acid) is one of two ketone derivatives of glutaric acid. (The term 'ketoglutaric acid,' when not further qualified, almost always refers to the alpha variant. β-Ketoglutaric acid varies only by the position of the ketone functional group, and is much less common.Acetyl-CoAOxaloacetateMalateFumarateSuccinateSuccinyl-CoACitratecis-AconitateIsocitrateOxalosuccinate2-oxoglutarate α-Ketoglutaric acid (2-oxoglutaric acid) is one of two ketone derivatives of glutaric acid. (The term 'ketoglutaric acid,' when not further qualified, almost always refers to the alpha variant. β-Ketoglutaric acid varies only by the position of the ketone functional group, and is much less common. Its anion, α-ketoglutarate (α-KG, also called 2-oxoglutarate, or 2OG) is an important biological compound. It is the keto acid produced by deamination of glutamate, and is an intermediate in the Krebs cycle. The alanine transaminase (ALT) enzyme converts α-Ketoglutarate and L-alanine to L-glutamate and pyruvate, respectively, as a reversible process. α-Ketoglutarate is a key intermediate in the Krebs cycle, coming after isocitrate and before succinyl CoA. Anaplerotic reactions can replenish the cycle at this juncture by synthesizing α-ketoglutarate from transamination of glutamate, or through action of glutamate dehydrogenase on glutamate. Glutamine is synthesized from glutamate by glutamine synthetase, which utilizes an ATP to form glutamyl phosphate; this intermediate is attacked by ammonia as a nucleophile giving glutamine and inorganic phosphate. Proline, Arginine, and Lysine(in limited organisms) are other amino acids synthesized as well. These three amino acids derive from glutamate with the addition of further steps or with the use of enzymes to facilitate reactions. Another function is to combine with nitrogen released in the cell, therefore preventing nitrogen overload. α-Ketoglutarate is one of the most important nitrogen transporters in metabolic pathways. The amino groups of amino acids are attached to it (by transamination) and carried to the liver where the urea cycle takes place. α-Ketoglutarate is transaminated, along with glutamine, to form the excitatory neurotransmitter glutamate. Glutamate can then be decarboxylated (requiring vitamin B6) into the inhibitory neurotransmitter GABA. It is reported that high ammonia and/or high nitrogen levels may occur with high protein intake, excessive aluminum exposure, Reye's syndrome, cirrhosis, and urea cycle disorder.