Alpha-Ketoglutaric acid

α-Ketoglutaric 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 oxo-glutarate) is an important biological compound. It is the keto acid produced by de-amination of glutamate, and is an intermediate in the Krebs cycle.

Krebs cycle
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.

Formation of amino acids
Glutamine is synthesized from glutamate by glutamine synthase, which utilizes an ATP to form glutamyl phosphate; this intermediate is attacked by ammonia as a nucleophile giving glutamine and inorganic phosphate.

Nitrogen transporter
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.

Relationship to molecular oxygen
Acting as a co-substrate, it also plays important function in oxidation reactions involving molecular oxygen.

Molecular oxygen (O2) directly oxidizes many compounds to produce useful products in an organism, such as antibiotics, etc., in reactions catalyzed by oxygenases. In many oxygenases, α-ketoglutarate helps the reaction by being oxidized together with the main substrate. In fact, one of the α-ketoglutarate-dependent oxygenases is an O2 sensor, informing the organism the oxygen level in its environment.

Dietary supplement
α-Ketoglutaric acid is sold as a dietary supplement and to body builders as AKG or a-KG with the claim that it improves peak athletic performance. This claim is based on studies that show extra ammonia in the body can combine with alpha-ketoglutarate to reduce problems associated with ammonia toxicity. However, the only studies that show alpha-ketoglutarate can reduce ammonia toxicity have been performed in hemodialysis patients.

Production
α-Ketoglutarate can be produced by:
 * Oxidative decarboxylation of isocitrate by isocitrate dehydrogenase;
 * Oxidative deamination of glutamate by glutamate dehydrogenase.

Alpha-ketoglutarate can be used to produce:
 * Creatine-alpha ketoglutarate