View source for Oxoglutarate dehydrogenase

{{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= 
}}

{{CMG}}



==Overview==
'''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 specificbranched-chain α-keto acids.

==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]] 

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 = | volume = | issue = | pages = | 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==
# 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:autoantigens]]

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