Oxoglutarate dehydrogenase
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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:
| Unit | EC number | Name | Gene | Coenzyme |
| E1 | EC 1.2.4.2 | oxoglutarate dehydrogenase | OGDH | thiamine pyrophosphate |
| E2 | EC 2.3.1.61 | dihydrolipoyl succinyltransferase | DLST | lipoic acid |
| E3 | EC 1.8.1.4 | dihydrolipoyl dehydrogenase | DLD | NAD+ |
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).
- CAS: 9031-02-1
Metabolic pathways
This enzyme participates in three different pathways:
- Citric acid cycle (KEGG link: MAP00020)
- Lysine degradation (KEGG link: MAP00310)
- Tryptophan metabolism (KEGG link: MAP00380)
Kinetic properties
The following values are from Azotobacter vinelandii (1):
- KM: 0.14 ± 0.04 mM
- Vmax : 9 ± 3 μmol.min-1.mg-1
Citric acid cycle
Reaction
The reaction catalyzed by this enzyme in the citric acid cycle is:
- α-ketoglutarate + NAD+ + CoA → Succinyl CoA + CO2 + NADH
This reaction proceeds in three steps:
- decarboxylation of α-ketoglutarate,
- oxidation,
- and subsequent transfer to CoA, which forms the end product, succinyl CoA.
ΔG°' for this reaction is -7.2 kcal mol-1. 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.[1] 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
- Oxoglutarate+dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH)
- ↑ Leung PS, Rossaro L, Davis PA; et al. (2007). "Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis". doi:10.1002/hep.21828. PMID 17657817.