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⁾:

• 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,
• 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

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.

External links

• MeSH Oxoglutarate+dehydrogenase

v • d • e 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

v • d • e Enzymes: multienzyme complexes

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 (HADHA, HADHB) - Oxoglutarate dehydrogenase - Phosphoenolpyruvate sugar phosphotransferase system - Photosynthetic reaction center complex proteins - Photosystem - Polyketide synthase - Pyruvate dehydrogenase complex (E1, E2, E3) - Sucrase-isomaltase complex -Tryptophan synthase

v • d • e 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

v • d • e Mitochondrial enzymes and transporters
Outer membrane	Long fatty acyl CoA synthetase - Kynureninase - Monoamine oxidase
Intermembrane space	Adenylate kinase - Creatine kinase
Inner membrane	Coenzyme Q - cytochrome c reductase -Cytochrome c - Dihydroorotate dehydrogenase -Glutamate aspartate transporter - Glycerol-3-phosphate dehydrogenase - NADH dehydrogenase - Succinate dehydrogenase
Matrix	Aconitase - Aspartate transaminase - ALDH2 - Carbamoyl phosphate synthase - Citrate synthase - Fumarase - Glutamate dehydrogenase - Isocitrate dehydrogenase - Malate dehydrogenase - Ornithine transcarbamoylase - Oxoglutarate dehydrogenase - Pyruvate dehydrogenase complex - Succinyl coenzyme A synthetase
Mitochondrial DNA	Complex I (7 units) - Complex III (1 unit) - Complex IV (3 units) - ATP synthase (2 units)

v • d • e 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)

it:Ossoglutarato deidrogenasi

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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 .