alpha-Ketoglutaric acid

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α-Ketoglutaric acid[1]
Alpha-ketoglutaric acid.png
Identifiers
CAS number 328-50-7 YesY
PubChem 51
ChemSpider 50 YesY
UNII 8ID597Z82X YesY
DrugBank DB02926
KEGG C00026 YesY
MeSH alpha-ketoglutaric+acid
ChEBI CHEBI:30915 YesY
ChEMBL CHEMBL1686 YesY
Jmol-3D images Image 1
Properties
Molecular formula C5H6O5
Molar mass 146.11 g/mol
Melting point 115 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

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 deamination of glutamate, and is an intermediate in the Krebs cycle.

Functions[edit]

Krebs cycle[edit]

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[edit]

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.

Nitrogen transporter[edit]

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.

It plays a role in detoxification of ammonia in brain.[2][3][4]

Relationship to molecular oxygen[edit]

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.

In combination with molecular oxygen, alpha-ketoglutarate is one of the requirements for the hydroxylation of proline to hydroxyproline in the production of Type 1 Collagen.

Dietary supplement[edit]

α-Ketoglutaric acids 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 excess ammonia in the body can combine with alpha-ketoglutarate, reducing problems associated with ammonia toxicity.[5] However, the only studies that show alpha-ketoglutarate can reduce ammonia toxicity have been performed in hemodialysis patients.[5]

Longevity[edit]

A study released on May 14, 2014 links α-ketoglutarate with significantly increased lifespan in nematode worms. [6]

Production[edit]

α-Ketoglutarate can be produced by:

Alpha-ketoglutarate can be used to produce:

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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TCACycle_WP78 go to article go to article go to article go to article go to HMDB go to article go to article go to article Go to article go to article go to article go to article go to article go to article Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article
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TCA Cycle edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". 

References[edit]

  1. ^ Merck Index, 13th Edition, 5320.
  2. ^ Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?
  3. ^ Ott, P; Clemmesen, O; Larsen, FS (Jul 2005). "Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis.". Neurochemistry international 47 (1-2): 13–8. doi:10.1016/j.neuint.2005.04.002. PMID 15921824. 
  4. ^ Hares, P; James, IM; Pearson, RM (May–Jun 1978). "Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog.". Stroke; a journal of cerebral circulation 9 (3): 222–4. doi:10.1161/01.STR.9.3.222. PMID 644619. 
  5. ^ a b Alpha-Ketoglutarate, WebMD
  6. ^ [1], nature