| 词条 | Alpha-Ketoglutaric acid |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 477319214 | Name = α-Ketoglutaric acid | Reference = [1] | ImageFile = Alpha-ketoglutaric_acid.png | ImageSize = 150px | PIN = 2-Oxopentanedioic acid | OtherNames = 2-Ketoglutaric acid alpha-Ketoglutaric acid 2-Oxoglutaric acid Oxoglutaric acid |Section1={{Chembox Identifiers | IUPHAR_ligand = 3636 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 50 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 8ID597Z82X | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C00026 | InChI = 1/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10) | InChIKey = KPGXRSRHYNQIFN-UHFFFAOYAN | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = KPGXRSRHYNQIFN-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 328-50-7 | PubChem = 51 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 30915 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = DB02926 | SMILES = O=C(O)C(=O)CCC(=O)O | MeSHName = alpha-ketoglutaric+acid |Section2={{Chembox Properties | Formula = C5H6O5 | MolarMass = 146.11 g/mol | Appearance = | Density = | MeltingPtC = 115 | MeltingPt_notes = | BoilingPt = |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} 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. FunctionsAlanine transaminaseThe alanine transaminase (ALT) enzyme converts α-Ketoglutarate and L-alanine to L-glutamate and pyruvate, respectively, as a reversible process. Krebs cycleα-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 acidsGlutamine 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.[2] These three amino acids derive from glutamate with the addition of further steps or with the use of enzymes to facilitate reactions. Nitrogen transporterAnother 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.[3][4][5] Relationship to molecular oxygenActing as a co-substrate for α-ketoglutarate-dependent hydroxylase, 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. Antioxidantα-Ketoglutarate, which is known to be released by several cell types, decreased the levels of hydrogen peroxide, and the α-ketoglutarate was depleted and converted to succinate in cell culture media.[6] LongevityA study released on May 14, 2014 links α-ketoglutarate with significantly increased lifespan in nematode worms. [7]Immune regulationA recent study has shown that α-ketoglutarate promotes TH1 differentiation and depletion of glutamine (by depleting its metabolite, α-ketoglutarate favors treg (regulatory T-cell) differentiation. It might play a role in skewing the balance in favor of tregs in the setting of the amino acid deprivation that can be seen in the tumor microenvironment.[8] Productionα-Ketoglutarate can be produced by:
Alpha-ketoglutarate can be used to produce:
Interactive pathway map{{TCACycle_WP78|highlight=Alpha-Ketoglutaric_acid}}See also
References1. ^Merck Index, 13th Edition, 5320. {{Citric acid cycle}}{{Amino acid metabolism intermediates}}{{DEFAULTSORT:Ketoglutaric Acid, Alpha-}}2. ^{{Cite journal|last=Ledwidge|first=Richard|last2=Blanchard|first2=John S.|title=The Dual Biosynthetic Capability ofN-Acetylornithine Aminotransferase in Arginine and Lysine Biosynthesis†|journal=Biochemistry|language=en|volume=38|issue=10|pages=3019–3024|doi=10.1021/bi982574a|pmid=10074354|year=1999}} 3. ^{{Cite web |url=http://www.autismstudies.info/AutismStudies.info/Fever_glutamine.html |title=Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel? |access-date=2014-05-19 |archive-url=https://web.archive.org/web/20140519184046/http://www.autismstudies.info/AutismStudies.info/Fever_glutamine.html |archive-date=2014-05-19 |dead-url=yes |df= }} 4. ^{{cite journal|last=Ott|first=P|author2=Clemmesen, O |author3=Larsen, FS |title=Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis.|journal=Neurochemistry International|date=Jul 2005|volume=47|issue=1–2|pages=13–8|pmid=15921824|doi=10.1016/j.neuint.2005.04.002}} 5. ^{{cite journal|last=Hares|first=P|author2=James, IM |author3=Pearson, RM |title=Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog.|journal=Stroke: A Journal of Cerebral Circulation|date=May–Jun 1978|volume=9|issue=3|pages=222–4|doi=10.1161/01.STR.9.3.222|pmid=644619|url=http://stroke.ahajournals.org/content/9/3/222.full.pdf}} 6. ^{{cite journal|last=Long|first=L|author2=Halliwell, B |title=Artefacts in cell culture: α-Ketoglutarate can scavenge hydrogen peroxide generated by ascorbate and epigallocatechin gallate in cell culture media.|journal=Biochemical and Biophysical Research Communications |date=2011 |volume=406 |issue=1 |pages=20–24 |doi=10.1016/j.bbrc.2011.01.091 |pmid=21281600}} 7. ^{{cite journal|doi=10.1038/nature13264 | title=The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR | journal=Nature| pmc=4263271| pmid=24828042| volume=510| issue=7505 | year=2014| pages=397–401 | last1 = Chin | first1 = RM | last2 = Fu | first2 = X | last3 = Pai | first3 = MY | last4 = Vergnes | first4 = L | last5 = Hwang | first5 = H | last6 = Deng | first6 = G | last7 = Diep | first7 = S | last8 = Lomenick | first8 = B | last9 = Meli | first9 = VS | last10 = Monsalve | first10 = GC | last11 = Hu | first11 = E | last12 = Whelan | first12 = SA | last13 = Wang | first13 = JX | last14 = Jung | first14 = G | last15 = Solis | first15 = GM | last16 = Fazlollahi | first16 = F | last17 = Kaweeteerawat | first17 = C | last18 = Quach | first18 = A | last19 = Nili | first19 = M | last20 = Krall | first20 = AS | last21 = Godwin | first21 = HA | last22 = Chang | first22 = HR | last23 = Faull | first23 = KF | last24 = Guo | first24 = F | last25 = Jiang | first25 = M | last26 = Trauger | first26 = SA | last27 = Saghatelian | first27 = A | last28 = Braas | first28 = D | last29 = Christofk | first29 = HR | last30 = Clarke | first30 = CF | last31 = Teitell | first31 = MA | last32 = Petrascheck | first32 = M | last33 = Reue | first33 = K | last34 = Jung | first34 = ME | last35 = Frand | first35 = AR | last36 = Huang | first36 = J}} 8. ^{{cite journal |last=Klysz |first=Dorota |last2=Tai |first2=Xuguang |date=29 Sep 2015 |title=Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation |url=http://stke.sciencemag.org/content/8/396/ra97 |journal=Science Signaling |volume=8 |issue=396 |pages=ra97 |doi=10.1126/scisignal.aab2610 |pmid=26420908 |access-date=14 October 2015}} 9. ^{{cite journal|last1=Richard|first1=Peter|last2=Hilditch|first2=Satu|title=d-Galacturonic acid catabolism in microorganisms and its biotechnological relevance|journal=Applied Microbiology and Biotechnology|volume=82|issue=4|year=2009|pages=597–604|issn=0175-7598|doi=10.1007/s00253-009-1870-6|pmid=19159926}} 3 : Dicarboxylic acids|Keto acids|Citric acid cycle compounds |
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