2-オキソグルタル酸デヒドロゲナーゼ
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/05 13:00:44」(JST)
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| oxoglutarate dehydrogenase |
| Identifiers |
| EC number |
1.2.4.2 |
| CAS number |
9031-02-1 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
|
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.
Contents
- 1 Units
- 2 Properties
- 2.1 Metabolic pathways
- 2.2 Kinetic properties
- 3 Citric acid cycle
- 3.1 Reaction
- 3.2 Regulation
- 4 Pathology
- 5 References
- 6 External links
Units
Much like pyruvate dehydrogenase complex (PDC), 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 |
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.
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):
- 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
Oxoglutarate dehydrogenase (α-Ketoglutarate dehydrogenase)
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
- ^ 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
External links
- Oxoglutarate dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Aldehyde/oxo oxidoreductases (EC 1.2)
|
|
| 1.2.1: NAD or NADP |
- Aldehyde dehydrogenase: Acetaldehyde dehydrogenase
- Long-chain-aldehyde dehydrogenase
- Glyceraldehyde 3-phosphate dehydrogenase
|
|
| 1.2.2: cytochrome |
- Formate dehydrogenase (cytochrome)
|
|
| 1.2.3: oxygen |
|
|
| 1.2.4: disulfide |
- Oxoglutarate dehydrogenase
- Pyruvate dehydrogenase
- Branched-chain alpha-keto acid dehydrogenase complex
|
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| 1.2.7: iron-sulfur protein |
|
|
- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
|
|
|
|
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Enzymes: multienzyme complexes
|
|
| Photosynthesis |
- Photosynthetic reaction center complex proteins
- Photosystem
|
|
| Dehydrogenase |
- Pyruvate dehydrogenase complex
- Oxoglutarate dehydrogenase
- Branched-chain alpha-keto acid dehydrogenase complex
|
|
| Other |
- CAD
- Carbamoyl phosphate synthase II
- Aspartate carbamoyltransferase
- Dihydroorotase
- Cholesterol side-chain cleavage enzyme
- Cytochrome b6f complex
- Electron transport chain
- Fatty acid synthetase complex
- Glycine decarboxylase complex
- Mitochondrial trifunctional protein
- Phosphoenolpyruvate sugar phosphotransferase system
- Polyketide synthase
- Sucrase-isomaltase complex
- Tryptophan synthase
|
|
|
Metabolism: Citric acid cycle enzymes
|
|
| Cycle |
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase
- Oxoglutarate dehydrogenase
- Succinyl CoA synthetase
- Succinate dehydrogenase (SDHA)
- Fumarase
- Malate dehydrogenase and ETC
|
|
| Anaplerotic |
|
to acetyl-CoA
|
- Pyruvate dehydrogenase complex (E1, E2, E3)
- (regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase)
|
|
|
to α-ketoglutaric acid
|
|
|
|
to succinyl-CoA
|
|
|
|
to oxaloacetate
|
- Pyruvate carboxylase
- Aspartate transaminase
|
|
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Mitochondrial
electron transport chain/
oxidative phosphorylation |
|
Primary
|
- Complex I/NADH dehydrogenase
- Complex II/Succinate dehydrogenase
- Coenzyme Q
- Complex III/Coenzyme Q - cytochrome c reductase
- Cytochrome c
- Complex IV/Cytochrome c oxidase
- Coenzyme Q10 synthesis: COQ2
- COQ3
- COQ4
- COQ5
- COQ6
- COQ7
- COQ9
- COQ10A
- COQ10B
- PDSS1
- PDSS2
|
|
|
Other
|
- Alternative oxidase
- Electron-transferring-flavoprotein dehydrogenase
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|
|
|
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
|
k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
|
m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
|
|
|
|
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Mitochondrial proteins
|
|
| Outer membrane |
| fatty acid degradation |
- Carnitine palmitoyltransferase I
- Long-chain-fatty-acid—CoA ligase
|
|
| tryptophan metabolism |
|
|
monoamine neurotransmitter
metabolism |
|
|
|
| Intermembrane space |
- Adenylate kinase
- Creatine kinase
|
|
| Inner membrane |
| oxidative phosphorylation |
- Coenzyme Q – cytochrome c reductase
- Cytochrome c
- NADH dehydrogenase
- Succinate dehydrogenase
|
|
| pyrimidine metabolism |
- Dihydroorotate dehydrogenase
|
|
| mitochondrial shuttle |
- Malate-aspartate shuttle
- Glycerol phosphate shuttle
|
|
| other |
- Glutamate aspartate transporter
- Glycerol-3-phosphate dehydrogenase
- ATP synthase
- Carnitine palmitoyltransferase II
- Uncoupling protein
|
|
|
| Matrix |
| citric acid cycle |
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase
- Oxoglutarate dehydrogenase complex
- 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 |
|
|
|
|
|
|
| Other/to be sorted |
| steroidogenesis |
- Cholesterol side-chain cleavage enzyme
- Steroid 11-beta-hydroxylase
- Aldosterone synthase
- Frataxin
|
|
- Mitochondrial membrane transport protein
- Mitochondrial permeability transition pore
- Mitochondrial carrier
|
|
|
| Mitochondrial DNA |
| Complex I |
- MT-ND1
- MT-ND2
- MT-ND3
- MT-ND4
- MT-ND4L
- MT-ND5
- MT-ND6
|
|
| Complex III |
|
|
| Complex IV |
|
|
| ATP synthase |
|
|
| tRNA |
- 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
|
|
|
|
see also mitochondrial diseases
B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)
|
|
|
Antigens: Autoantigens
|
|
| Dehydrogenase |
- Branched-chain alpha-keto acid dehydrogenase complex
- Oxoglutarate dehydrogenase
- Pyruvate dehydrogenase
|
|
| Transglutaminase |
- Epidermal transglutaminase
- Tissue transglutaminase
|
|
| Nucleoporins |
- NUP35
- NUP37
- NUP43
- NUP50
- NUP54
- NUP62
- NUP85
- NUP88
- NUP93
- NUP98
- NUP107
- NUP133
- NUP153
- NUP155
- NUP160
- NUP188
- NUP210
- NUP205
- NUP214
|
|
| Other |
- Acetylcholine receptor
- Actin
- Apolipoprotein H
- Cardiolipin
- Centromere
- Filaggrin (Citrullinate)
- Gangliosides
- Sp100 nuclear antigen
- Thrombin
- Topoisomerase
|
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cell/phys/auag/auab/comp, igrc
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UpToDate Contents
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English Journal
- The glyoxylate shunt is essential for CO2-requiring oligotrophic growth of Rhodococcus erythropolis N9T-4.
- Yano T1, Yoshida N, Yu F, Wakamatsu M, Takagi H.
- Applied microbiology and biotechnology.Appl Microbiol Biotechnol.2015 Jul;99(13):5627-37. doi: 10.1007/s00253-015-6500-x. Epub 2015 Mar 10.
- Rhodococcus erythropolis N9T-4 shows extremely oligotrophic growth requiring atmospheric CO2 and forms its colonies on an inorganic basal medium (BM) without any additional carbon source. Screening of a random mutation library constructed by a unique genome deletion method that we established indica
- PMID 25750047
- A new role for α-ketoglutarate dehydrogenase complex: regulating metabolism through post-translational modification of other enzymes.
- McKenna MC1, Rae CD2.
- Journal of neurochemistry.J Neurochem.2015 Jul;134(1):3-6. doi: 10.1111/jnc.13150. Epub 2015 Jun 4.
- This Editorial highlights a study by Gibson et al. published in this issue of JNeurochem, in which the authors reveal a novel role for the α-ketoglutarate dehydrogenase complex (KGDHC) in post-translational modification of proteins. KGDHC may catalyze post-translational modification of itself as w
- PMID 26052752
- Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines.
- Gibson GE1, Xu H1, Chen HL1, Chen W2, Denton TT3, Zhang S2.
- Journal of neurochemistry.J Neurochem.2015 Jul;134(1):86-96. doi: 10.1111/jnc.13096. Epub 2015 Apr 8.
- Reversible post-translation modifications of proteins are common in all cells and appear to regulate many processes. Nevertheless, the enzyme(s) responsible for the alterations and the significance of the modification are largely unknown. Succinylation of proteins occurs and causes large changes in
- PMID 25772995
Japanese Journal
- The effects of introduction of a fungal glutamate dehydrogenase gene (gdhA) on the photosynthetic rates, biomass, carbon and nitrogen contents in transgenic potato
- Changes in Enzyme Activities at the Pyruvate Node in Glutamate-Overproducing Corynebacterium glutamicum(MICROBIAL PHYSIOLOGY AND BIOTECHNOLOGY)
- Changes in Enzyme Activities at the Pyruvate Node in Glutamate-Overproducing Corynebacterium glutamicum
Related Links
- The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). It contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1 ...
- ... Frank RA, Price AJ, Northrop FD, Perham RN, Luisi BF. Crystal structure of the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex. J Mol Biol. 2007 May 4;368(3):639-51. Epub 2007 ↑ ...
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脱水素酵素 デヒドロゲナーゼ
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脱水素酵素 デヒドロゲナーゼ