Editing Α-Ketoglutaric acid (section)

===Metabolic interactions===
====Citric acid cycle====
α-Ketoglutarate is a component of the [[citric acid cycle]], a cyclical metabolic pathway located in the [[mitochondria]]. This cycle supplies the energy that cells need by sequentially [[metabolizing]] (indicated by <big>→</big>) citrate through seven intermediate metabolites and then converting the eighth intermediate metabolite, oxaloacetate, back to citrate:<ref name="pmid23378250"/>

:::::'''[[citrate]] <big>→</big> [[Aconitic acid|cis-aconitate]] <big>→</big> [[Isocitric acid|isocitrate]] <big>→</big> α-ketoglutarate <big>→</big> [[succinyl-CoA]] <big>→</big> [[succinate]] <big>→</big> [[Fumaric acid|fumarate]] <big>→</big> [[malate]] <big>→</big> [[oxaloacetate]] <big>→</big> [[citrate]]'''

In this cycle, the enzyme [[isocitrate dehydrogenase|isocitrate dehydrogenase 3]] converts isocitrate (isocitrate has 4 isomers of which only the (−)-d-threo-isomer is the naturally occurring isomer in the citric acid cycle.<ref name="pmid29568744">{{cite journal | vauthors = Kamzolova SV, Shamin RV, Stepanova NN, Morgunov GI, Lunina JN, Allayarov RK, Samoilenko VA, Morgunov IG | title = Fermentation Conditions and Media Optimization for Isocitric Acid Production from Ethanol by Yarrowia lipolytica | journal = BioMed Research International | volume = 2018 | issue = | pages = 2543210 | date = 2018 | pmid = 29568744 | pmc = 5820659 | doi = 10.1155/2018/2543210 | doi-access = free | url = }}</ref>) to α-ketoglutarate which in the next step is converted to succinyl-CoA by the [[oxoglutarate dehydrogenase complex]] of enzymes. 

Aside from the citric acid cycle, α-ketoglutarate is made by '''a)''' [[glutaminolysis]] in which the enzyme [[glutaminase]] removes the [[amino group]] from [[glutamine]] to form glutamate which is converted to α-ketoglutarate by any one of three enzymes, [[glutamate dehydrogenase]], [[alanine transaminase]], or [[aspartate transaminase]] (see [[Glutaminolysis|The glutaminolytic pathway]]s); and various [[pyridoxal phosphate]]-dependent [[transamination]] reactions mediated by, e.g., the [[alanine transaminase]] enzyme,<ref name="pmid19085960">{{cite journal | vauthors = Yang RZ, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, Rajamohan F, Qian K, Liu L, Gong DW | title = Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity | journal = Hepatology | volume = 49 | issue = 2 | pages = 598–607 | date = February 2009 | pmid = 19085960 | pmc = 2917112 | doi = 10.1002/hep.22657 | url = }}</ref> in which glutamate is converted to α-Ketoglutarate by "donating" its {{chem2|\sNH2}} to other compounds (see [[transamination]]).<ref name="pmid26759695"/><ref name="pmid34952764">{{cite journal | vauthors = Gyanwali B, Lim ZX, Soh J, Lim C, Guan SP, Goh J, Maier AB, Kennedy BK | title = Alpha-Ketoglutarate dietary supplementation to improve health in humans | journal = Trends in Endocrinology and Metabolism | volume = 33 | issue = 2 | pages = 136–146 | date = February 2022 | pmid = 34952764 | doi = 10.1016/j.tem.2021.11.003 | hdl = 1871.1/4ada9cac-6437-44d5-ad2b-c0ee6431df3b | url = | hdl-access = free }}</ref> Acting in these pathways, α-ketoglutarate contributes to the production of amino acids such as [[glutamine]], [[proline]], [[arginine]], and [[lysine]] as well as the lowering of cellular carbon and nitrogen (i.e., N) levels; this prevents excessive levels of these two potentially toxic [[Chemical element|elements]] from accumulating in cells and tissues.<ref name="pmid29750149"/><ref name="pmid19085960"/><ref name="pmid34952764"/> The [[neurotoxin]], [[ammonia]] (i.e., {{Chem2|NH3}}), is also prevented form accumulating in tissues. In this metabolic pathway the {{chem2|\sNH2}} group on an amino acid is transferred to α-ketoglutarate; this forms the α-keto acid of the original amino acid and the amine-containing product of α-ketoglutarate, glutamate. The celllular glutamate passes into the circulation and is taken up by the liver where it delivers its acquired {{chem2|\sNH2}} group to the [[urea cycle]]. In effect, the latter pathway removes excess ammonia from the body in the form of urinary [[urea]].<ref name="pmid29750149"/><ref name="pmid35500655"/><ref>{{Cite journal |last=Katayama |first=Kazuhiro |date=2004-12-01 |title=Ammonia metabolism and hepatic encephalopathy |url=https://www.sciencedirect.com/science/article/pii/S138663460400227X |journal=Hepatology Research |volume=30 |pages=73–80 |doi=10.1016/j.hepres.2004.08.013 |pmid=15607143 |issn=1386-6346}}</ref>

====Reactive oxygen species====
α-Ketoglutarate is one of the non-enzymatic antioxidant agents. It reacts with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to form [[succinate]], carbon dioxide (i.e., {{chem2|CO2}}), and water (i.e., ({{chem2|H2O}}) thereby lowering the levels of H<sub>2</sub>O<sub>2</sub>. Additionally, α-ketoglutarate increases the activity of [[superoxide dismutase]], which converts the highly toxic ({{chem|O|2|-}}) [[radical (chemistry)|radical]] to molecular [[oxygen]] (i.e., O<sub>2</sub>) and {{chem|H|2|O|2}}.<ref name="pmid29750149"/><ref name="pmid35500655"/>

====Formation of the neurotransmitter gamma-aminobutyric acid====
A study conducted on the [[GABAergic]] [[neurons]] (i.e., nerve cells) in the [[neocortex]] of rat brains reported that the [[cytosol]]ic form of the [[aspartate transaminase]] enzyme metabolizes α-ketoglutarate to [[glutamate]] which in turn is metabolized by [[glutamic acid decarboxylase]] to the [[Neurotransmitter#Modulation|inhibitory neurotransmitter]] [[gamma-aminobutyric acid]]. These metabolic reactions occur at the ends of the inhibitory [[axons]] of the GABAergic neurons and result in the release of gamma-aminobutyric acid which then inhibits the activation of nearby neurons.<ref name="pmid7838383"/><ref name="pmid32002773">{{cite journal | vauthors = Robinson MB, Lee ML, DaSilva S | title = Glutamate Transporters and Mitochondria: Signaling, Co-compartmentalization, Functional Coupling, and Future Directions | journal = Neurochemical Research | volume = 45 | issue = 3 | pages = 526–540 | date = March 2020 | pmid = 32002773 | pmc = 7060825 | doi = 10.1007/s11064-020-02974-8 | url = }}</ref>