Oxoglutarate dehydrogenase 1416951 214453338 2008-05-23T16:56:56Z DOI bot 6652755 Citation enhancement. IN TRIAL: please check edit and [[User:DOI_bot/bugs|report any bugs]]. Any concerns? Please [[User_talk:Smith609|Contact the bot's operator]]. {{Protbox |Name=2-oxoglutarate dehydrogenase E1 component (α-Ketoglutarate dehydrogenase) |Photo= |Caption= | HGNCid = 8124 | Symbol = OGDH |AltSymbols = |Names=''' Alpha-ketoglutarate dehydrogenase''' | Chromosome = 7 | Arm = p | Band = 13 | LocusSupplementaryData = -p11.2 |Gene= |Gene_type=[[protein]] coding |Protein_length= |Molecular_weight=115942 |Structure= |Type=Enzyme: [[Dehydrogenase]] |Functions=converts [[Ketoglutaric acid|Alpha ketoglutarate]] to [[succinyl CoA]] |Domains= [[Transketolase]] central region, [[Dehydrogenase]] E1 component |Motifs= |Alternative_products= |Catalytic_activity=2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + [[Carbon dioxide|CO(2)]] |Cofactors=[[Thiamine pyrophosphate]] [[lipoate]], [[FAD]], [[NAD]], [[CoA]] |Enzyme_regulation=Catabolite repressed |Biophysicochemical_properties= |Diseases=Alpha-Ketoglutarate Dehydrogenase Deficiency |Pharmaceuticals= |Biotechnology= |Taxa= ''[[Homo sapiens]]''; homologs: [[ubiquitous]] among oxidatively respiring organisms |Cells= ubiquitous among aerobic cells |Location=[[mitochondrion]], [[mitochondrial matrix]] |Mods= |Pathways=[[Citric acid cycle]], [[Lysine degradation]], [[Tryptophan metabolism]] |Interactions= |Actions= |Agonists= |Antagonists= |EntrezGene = |OMIM = |RefSeq = |UniProt = |PDB = | ECnumber = 1.2.4.2 |Codes= {{EntrezGene|4967}}; {{OMIM|203740}}; {{RefSeq|NM_001003941}}; {{UniProt|Q02218}} |Pages= |Review= }} '''Oxoglutarate dehydrogenase''' (aka '''α-ketoglutarate dehydrogenase''') is an enzyme complex most commonly known for its role in the [[citric acid cycle]]. ==Units== Much like [[pyruvate dehydrogenase complex]], this enzyme forms a complex composed of three components: {| class="wikitable" | '''Unit''' || '''EC number''' || '''Name''' || '''Gene''' || '''[[Coenzyme]]''' |- | E<sub>1</sub> || {{EC number|1.2.4.2}} || oxoglutarate dehydrogenase || {{Gene|OGDH}} || [[thiamine pyrophosphate]] |- | E<sub>2</sub> || {{EC number|2.3.1.61}} || dihydrolipoyl succinyltransferase || {{Gene|DLST}} || [[lipoic acid]] |- | E<sub>3</sub> || {{EC number|1.8.1.4}} || dihydrolipoyl dehydrogenase || {{Gene|DLD}} || [[nicotinamide adenine dinucleotide|NAD<sup>+</sup>]] |} In fact, three classes of these multienzyme complexes have been characterized, one specific for [[pyruvate]], a second specific for [[2-oxoglutarate]] and a third specific [[branched-chain α-keto acid]]s. ==Properties== ===Nomenclature and classification=== The official name of this enzyme is oxoglutarate dehydrogenase (OGDC) although it is also commonly known as α-ketoglutarate dehydrogenase (AKGDH). *[[Chemical Abstracts Service|CAS]]: 9031-02-1 ===Metabolic pathways=== This enzyme participates in three different pathways: * [[Citric acid cycle]] (KEGG link: [http://www.genome.jp/kegg/pathway/map/map00720.html MAP00020]) * [[Lysine]] degradation (KEGG link: [http://www.genome.jp/kegg/pathway/map/map00310.html MAP00310]) * [[Tryptophan]] metabolism (KEGG link: [http://www.genome.jp/kegg/pathway/map/map00380.html MAP00380]) ===Kinetic properties=== The following values are from ''[[Azotobacter vinelandii]]''&nbsp;<sup>(1)</sup>: *[[Michaelis-Menten kinetics|K<sub>M</sub>]]: 0.14 ± 0.04 mM *V<sub>max</sub> : 9 ± 3 μmol.min<sup>-1</sup>.mg<sup>-1</sup> ==Citric acid cycle== ===Reaction=== The reaction catalyzed by this enzyme in the citric acid cycle is: :[[α-ketoglutarate]] + [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]] + [[Coenzyme A|CoA]] → [[Succinyl CoA]] + [[Carbon dioxide|CO<sub>2</sub>]] + [[NADH]] [[Image:Oxoglutarate dehydrogenase (α-Ketoglutarate dehydrogenase).png|thumb|500px|center|Oxoglutarate dehydrogenase (α-Ketoglutarate dehydrogenase)]] This reaction proceeds in three steps: * [[decarboxylation]] of α-ketoglutarate, * [[oxidation]], * and subsequent transfer to [[Coenzyme A|CoA]], which forms the end product, [[succinyl CoA]]. [[Gibbs free energy|ΔG°']] for this reaction is -7.2 kcal mol<sup>-1</sup>. The energy needed for this oxidation is conserved in the formation of a thioester bond of [[succinyl CoA]]. ===Regulation=== Oxoglutarate dehydrogenase is a key control point in the citric acid cycle. It is inhibited by its products, [[succinyl CoA]] and [[NADH]]. A high energy charge in the cell will also be inhibitive. ==Pathology== 2-Oxo-glutarate dehydrogrenase is an [[autoantigen]] recognized in [[primary biliary cirrhosis]], a form of acute liver failure. These [[antibodies]] appear to recognize oxidized [[protein]] that has resulted from inflamatory immune responses. Some of these inflamatory responses are explained by [[gluten sensitivity]].<ref name="pmid17657817">{{cite journal | author = Leung PS, Rossaro L, Davis PA, ''et al'' | title = Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis | journal = Hepatology| volume = 46| issue = | pages = 1436| year = 2007 | pmid = 17657817 | doi = 10.1002/hep.21828}}</ref> Other mitochondrial autoantigens include [[pyruvate dehydrogenase]] and [[branched-chain alpha-keto acid dehydrogenase complex]], which are antigens recognized by [[anti-mitochondrial antibodies]]. ==References== <references /> # Bunik V, Westphal AH, de Kok A: ''Kinetic properties of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii evidence for the formation of a precatalytic complex with 2-oxoglutarate.'' Eur J Biochem 2000; 267(12): 3583-91. PMID 10848975. ==External links== * {{MeshName|Oxoglutarate+dehydrogenase}} {{Aldehyde/Oxo oxidoreductases}} {{Multienzyme complexes}} {{Citric acid cycle enzymes}} {{Mitochondrial enzymes}} {{Autoantigens}} [[Category:EC 1.2.4]] [[Category:autoantigens]] [[it:Ossoglutarato deidrogenasi]]