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.
Much like pyruvate dehydrogenase complex (PDC), this enzyme forms a complex composed of three components:
Unit EC number Name Gene Coenzyme E1 EC 184.108.40.206 oxoglutarate dehydrogenase OGDH thiamine pyrophosphate E2 EC 220.127.116.11 dihydrolipoyl succinyltransferase DLST lipoic acid E3 EC 18.104.22.168 dihydrolipoyl dehydrogenase DLD FAD
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.
This enzyme participates in three different pathways:
- Citric acid cycle (KEGG link: MAP00020)
- Lysine degradation (KEGG link: MAP00310)
- Tryptophan metabolism (KEGG link: MAP00380)
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
The reaction catalyzed by this enzyme in the citric acid cycle is:
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.
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.
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. 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.
- ^ 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.
- 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
- 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
- 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
Aldehyde/oxo oxidoreductases (EC 1.2) 1.2.1: NAD or NADP 1.2.2: cytochrome 1.2.3: oxygen 1.2.4: disulfide 1.2.7: iron-sulfur protein Metabolism: Citric acid cycle enzymes Cycle Anapleroticto acetyl-CoAto succinyl-CoAto oxaloacetate Mitochondrial
electron transport chain/
Mitochondrial proteins Outer membrane Intermembrane space Inner membraneGlutamate aspartate transporter, Glycerol-3-phosphate dehydrogenase, ATP synthase, Carnitine palmitoyltransferase II, Uncoupling protein) Matrix
alcohol metabolism (ALDH2)PMPCB
Other/to be sorted Mitochondrial DNAtRNA (MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY) Antigens: Autoantigens Dehydrogenase Transglutaminase Nucleoporins Other
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