Oxoglutarate dehydrogenase
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| 2-oxoglutarate dehydrogenase E1 component (α-Ketoglutarate dehydrogenase) | |
|---|---|
| Symbol(s): | OGDH |
| Other names: | Alpha-ketoglutarate dehydrogenase |
| Genetic data | |
| Locus: | Chr. 7 p13-p11.2 |
| Gene type: | protein coding |
| Protein Structure/Function | |
| Molecular Weight: | 115942 (Da) |
| Protein type: | Enzyme: Dehydrogenase |
| Functions: | converts Alpha ketoglutarate to succinyl CoA |
| Domains: | Transketolase central region, Dehydrogenase E1 component |
| Other | |
| Taxa expressing: | Homo sapiens; homologs: ubiquitous among oxidatively respiring organisms |
| Cell types: | ubiquitous among aerobic cells |
| Subcellular localization: | mitochondrion, mitochondrial matrix |
| Pathway(s): | Citric acid cycle, Lysine degradation, Tryptophan metabolism |
| Enzymatic Data | |
| Catalytic activity: | 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO(2) |
| Cofactor(s): | Thiamine pyrophosphate lipoate, FAD, NAD, CoA |
| Enzyme Regulation: | Catabolite repressed |
| Medical/Biotechnological data | |
| Diseases: | Alpha-Ketoglutarate Dehydrogenase Deficiency |
| Database Links | |
| EC number: | 1.2.4.2 |
| Codes: | EntrezGene 4967; Online 'Mendelian Inheritance in Man' (OMIM) 203740; RefSeq NM_001003941; UniProt Q02218 |
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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 specific branched-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
Aldehyde/oxo oxidoreductases (EC 1.2) | |
|---|---|
| 1.2.1 - NAD or NADP acceptor | Aldehyde dehydrogenase - Acetaldehyde dehydrogenase (ALDH2) - Glyceraldehyde 3-phosphate dehydrogenase - Long-chain-aldehyde dehydrogenase |
| 1.2.4 - disulfide acceptor | Oxoglutarate dehydrogenase - Pyruvate dehydrogenase - Branched-chain alpha-keto acid dehydrogenase complex |
Metabolism: Citric acid cycle enzymes | |
|---|---|
| Cycle | Citrate synthase - Aconitase - Isocitrate dehydrogenase - Oxoglutarate dehydrogenase - Succinyl CoA synthetase Succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD) - Fumarase - Malate dehydrogenase |
| Anaplerotic | to acetyl-CoA: Pyruvate dehydrogenase complex (regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase)
to ketoglutaric acid: Glutamate dehydrogenase to succinyl-CoA: Methylmalonyl-CoA mutase to oxaloacetate: Pyruvate carboxylase - Aspartate transaminase |
Antigens: Autoantigens |
|---|
| Acetylcholine receptor - Actin - Apolipoprotein H - Branched-chain alpha-keto acid dehydrogenase complex - Cardiolipin - Centromere - Epidermal transglutaminase - gangliosides - Oxoglutarate dehydrogenase - Sp100 nuclear antigen - Pyruvate dehydrogenase - Thrombin - Tissue transglutaminase - Topoisomerase - Nucleoporins (Nucleoporin-62 - Nucleoporin-210) |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
