Oxoglutarate dehydrogenase complex

The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.

Units

Much like pyruvate dehydrogenase complex (PDC), 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 for branched-chain α-keto acids.

Properties

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⁾:

• K_M: 0.14 ± 0.04 mM
• V_max : 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,
• reduction of NAD⁺ to NADH,
• 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. ADP and calcium ions are allosteric activators of the enzyme.

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. Activity of the 2-oxoglutarate dehydrogenase complex is decreased in many neurodegenerative diseases.

References

1. ^ 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. 

1. 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.
2. Bunik VI, Strumilo S: "Regulation of Catalysis Within Cellular Network: Metabolic and Signaling Implications of the 2-Oxoglutarate Oxidative Decarboxylation." Current Chemical Biology, 2009, 3: 279-290
3. Bunik VI, Fernie AR: "Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation." Biochem. J. 2009, 422: 405–421
4. L. Trofimova, M. Lovat, A. Groznaya, E. Efimova, T. Dunaeva, M. Maslova, A. Graf, and V. Bunik: "Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate: Implications into the Role of the Complex in Neurodegenerative Diseases." International Journal of Alzheimer Disease 2010; Volume 2010, Article ID 749061, 8 pages, doi:10.4061/2010/749061, http://www.sage-hindawi.com/journals/ijad/2010/749061.html

External links

• MeSH Oxoglutarate+dehydrogenase