ALPHA-KETOGLUTARIC ACID

'Alpha-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. Beta-ketoglutaric acid varies only by the position of the ketone functional group, and is much less common.)
Its anion, 'Alpha-ketoglutarate' (also called 'oxo-glutarate') is an important biological compound. It is the keto acid produced by de-amination of glutamate, an is an intermediate in the Krebs cycle.

Contents

Functions

Krebs cycle

Formation of amino acids

Nitrogen transporter

Relationship to molecular oxygen

Dietary supplement

Production

References

External links

Functions

Krebs cycle

It 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 Alpha-ketoglutarate.

Formation of amino acids

One of its functions is to combine with ammonia to form glutamic acid and then glutamine.

Nitrogen transporter

Another function is to combine with nitrogen released in the cell, therefore preventing nitrogen overload.
Alpha-ketoglutarate is one of the most important nitrogen transporter 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.
Alpha-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, autism, Reye's syndrome, cirrhosis & 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, alpha-ketoglutarate helps the reaction by being oxidized together with the main substrate. In fact, one of the alpha-ketoglutarate-dependent oxygenases is an O₂ sensor, informing the organism the oxygen level in its environment.

Dietary supplement

Alpha-ketoglutaric acid is sold as a dietary supplement and to body builders as AKG or a-KG. Some believe it increases stamina.

Production

Alpha-ketoglutarate can be produced by

★ Oxidative decarboxylation of isocitrate by isocitrate dehydrogenase;

★ Oxidative deamination of glutamate by glutamate dehydrogenase.

References

''Merck Index'', 13th Edition, '5320'.

External links