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Oxoglutarate dehydrogenase (aka a-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:
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 a-keto acids.
Properties
Nomenclature and classification
The official name of this enzyme is oxoglutarate dehydrogenase (OGDC) although it is also commonly known as a-ketoglutarate dehydrogenase (AKGDH).
Metabolic pathways
This enzyme participates in three different pathways:
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:
- a-ketoglutarate + NAD+ + CoA ? Succinyl CoA + CO2 + NADH
Oxoglutarate dehydrogenase (a-Ketoglutarate dehydrogenase)
This reaction proceeds in three steps:
?G°' 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 inflammatory immune responses. Some of these inflammatory 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
- ^ Leung PS, Rossaro L, Davis PA, et al (2007). "Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis". Hepatology 46: 1436. doi:10.1002/hep.21828. PMID 17657817.
- 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
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Mitochondrial enzymes and transporters |
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| Outer membrane |
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| Intermembrane space |
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| Inner membrane |
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citric acid cycle ( Citrate synthase, Aconitase, Isocitrate dehydrogenase, Oxoglutarate dehydrogenase, Succinyl coenzyme A synthetase, Fumarase, Malate dehydrogenase)
anaplerotic reactions (Aspartate transaminase, Glutamate dehydrogenase, Pyruvate dehydrogenase complex)
urea cycle (Carbamoyl phosphate synthetase I, Ornithine transcarbamylase, N-Acetylglutamate synthase)
alcohol metabolism ( ALDH2)
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| Other/to be sorted |
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| Mitochondrial DNA |
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