1.2.1.105: 2-oxoglutarate dehydrogenase system
This is an abbreviated version!
For detailed information about 2-oxoglutarate dehydrogenase system, go to the full flat file.
Word Map on EC 1.2.1.105
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1.2.1.105
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kgdhc
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dihydrolipoamide
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thiamin
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alpha-ketoacids
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2-oxoadipate
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transsuccinylase
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charcot-marie-tooth
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2-aminoadipic
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medicine
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thiokinase
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glutaryl-coa
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analysis
- 1.2.1.105
- kgdhc
- dihydrolipoamide
- thiamin
- alpha-ketoacids
- 2-oxoadipate
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transsuccinylase
- charcot-marie-tooth
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2-aminoadipic
- medicine
- thiokinase
- glutaryl-coa
- analysis
Reaction
Synonyms
2-OGDH2, 2-oxoglutarate dehydrogenase, 2-oxoglutarate dehydrogenase complex, alpha-KDE2, alpha-ketoglutarate dehydrogenase, alpha-ketoglutarate dehydrogenase complex, alpha-KGDH, At3g55410, At5g65750, DHTKD1, dihydrolipoyl succinyltransferase E2, E1a, E1k, E1o, E2, KGDH, KGDHC, More, MPA24.10, ODGH, ODGH1, ODGH2, ODH, OGDC, OGDH, OGDHC, OGDHL, OGHDC-E2, PDHC, SucA, SucB
ECTree
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Inhibitors
Inhibitors on EC 1.2.1.105 - 2-oxoglutarate dehydrogenase system
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((+/-)-2-[4-((3-chloro-5-(trifluoromethyl)-2-pyridyl)oxy)-phenoxy]propionic acid)
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i.e. haloxyfop, grass-specific herbicide
2-oxo-3-methyl-n-valeric acid
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inhibition of the 2-oxoglutarate dehydrogenase enzyme complex in vivo and in situ, after 40 min 25% inhibition at 10 mM, 46% at 20 mM, after 80 min 58% inhibition at 10 mM, 80% at 20 mM, inhibition does not affect the mitochondrial membrane potential
7-(1-hydroxy-2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid
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time-dependent inhibition of the 2-oxoglutarate dehydrogenase complex appears to be related to the oxidation of 7-(1-hydroxy-2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid, catalyzed by an unknown component of the inner mitochondrial membrane, to electrophilic intermediates which bind covalently to active site cysteinyl residues of the enzyme complex
7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid
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may be an endotoxin that contributes to the alpha-oxoglutarate dehydrogenase and complex I defects in Parkinsons disease, the inhibition of the 2-oxoglutarate dehydrogenase complex is dependent on the oxidation of 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid, catalyzed by an unknown constituent of the inner mitochondrial membrane, to an electrophilic o-quinone imine that covalently modifies active site sulfhydryl residues
ADP
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the Sa0.5 for ADP in the absence of Ca2+ decreases as ionic strength increases. In the presence of calcium and 0.2 M ionic strength, ADP has no effect on 2-oxoglutarate dehydrogenase complex activity
Ca2+
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0.01 mM, decreases the concentration of 2-oxoglutarate required for half-maximal activity, inhibition at higher concentrations
cisplatin
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treatment with 0.05 or 0.1 mM for 3 h, followed by removal of cisplatin from the medium for 24 h, results in a pronounced loss of activity, both in mitochondrial aspartate aminotransferase-transfected cells and control cells, exposure to 0.1 mM results in a significantly greater loss of activity in mitochondrial aspartate aminotransferase-transfected cells than in control cells
ethyl 4-[ethoxy(hydroxy)phosphoryl]-4-oxobutanoate
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only inhibitory after preincubation, release of charged groups by cellular esterases and activation in intact cells
hydrogen peroxide
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the E2 subunit of alpha-ketoglutarate dehydrogenase is reversibly glutathionylated and inhibited by 0.025 mM hydrogen peroxide, the enzyme is maximally inhibited (about 45%) 5.0 min after the addition of H2O2
Na2HPO4
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50 mM KCl, 38% inhibition of the 2-oxoglutarate dehydrogenase complex
Na2SO4
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50 mM KCl, 4.5% inhibition of the 2-oxoglutarate dehydrogenase complex
NEM
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prevents desuccinylation of the 2-oxoglutarate dehydrogenase complex
palmitoyl-CoA
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is 10-fold less potent than phytanoyl-CoA, no inhibitory effect up to 0.3 mM
phytanoyl-CoA
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is 10-fold more potent than palmitoyl-CoA, no inhibitory effect up to 0.3 mM
succinyl phosphonate carboxy ethyl ester
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potent, slow-binding inhibitor of the 2-oxoglutarate dehydrogenase complex, complete inhibition at 0.1 mM
succinyl phosphonate diethyl ester
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poor inhibitor of the 2-oxoglutarate dehydrogenase complex
succinyl phosphonate phosphono ethyl ester
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poor inhibitor of the 2-oxoglutarate dehydrogenase complex
triethyl ester of succinyl phosphonate
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only inhibitory after preincubation, release of charged groups by cellular esterases and activation in intact cells
Tris-HCl
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50 mM, 26% inhibition of the 2-oxoglutarate dehydrogenase complex
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0.01 mM completely inhibits even in the presence of a 200fold higher concentration of its substrate 2-oxoglutarate
4-oxo-4-phosphonobutanoic acid
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affects (1-13C)glucose and (U-13C)glutamate metabolism, phosphonoethyl and carboxy ethyl ester reduce the concentration of aspartate, alanine and gamma-aminobutyric acid, phosphonoethyl ester reduces gluthatione content, carboxy ethyl ester reduces the intracellular concentration of valine and leucine
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0.01 mM completely inhibits even in the presence of a 200fold higher concentration of its substrate 2-oxoglutarate
4-[(2-carboxyethoxy)(hydroxy)phosphoryl]-4-oxobutanoic acid
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0.01 mM produce 70% inhibition
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0.01 mM completely inhibits even in the presence of a 200fold higher concentration of its substrate 2-oxoglutarate
4-[ethoxy(hydroxy)phosphoryl]-4-oxobutanoic acid
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0.01 mM produce 70% inhibition
ATP
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the magnitude of inhibition by ATP is not influenced by changes in ionic strength in the absence of calcium. In the presence of Ca2+, increases in ionic strength lower the inhibitory effects of ATP. The S0.5 for ATP in both presence and absence of Ca2+ is not affected by changes in ionic strength in the range of 0.1-0.2 M
H2O2
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addition outside of cells reduces KGDHC activity in proportion to the increase in reactive oxygen species
H2O2
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inhibits lysate KGDHC in a concentration- and time-dependent manner, inhibitory effect reversed by addition of dithiothreitol
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myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vivo
hypochlorous acid
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inhibits at concentrations ca. 50 times less than the effective mono-N-chloramine concentrations; myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vitro
K+
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50 mM KCl, 63% inhibition of the 2-oxoglutarate dehydrogenase complex
KMV
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inhibits KGDHC in PC-12 cells and does not alter mitochondrial membrane potential, but is associated with the release of cytochrome-c from mitochondria into the cytosol, reduction in basal cytosolic Ca2+, and diminishing endoplasmic reticulum calcium stores
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myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vivo
mono-N-chloramine
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inhibits both lysate and in situ KGDHC activities in a concentration-dependent manner in three distinct phases
mono-N-chloramine
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inhibits in a time- and concentration-dependent manner; myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vitro
Na+
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50 mM NaCl, 34% inhibition of the 2-oxoglutarate dehydrogenase complex
NADH
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0.1 mM, 50% inhibition. 0.2 mM AMP completely overcomes the inhibition
NADH
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directly inhibits the partial reaction catalyzed by the resolved 2-oxoglutarate dehydrogenase component. Ca2+, ADP or NAD+ decrease NADH inhibition
NH4+
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3 mM NH4Cl, enzyme activity in nonsynaptic mitochondria: 21% decrease of Vmax, 35% decrease of Km for 2-oxoglutarate. In synaptic mitochondria thioacetamide-induced encephalopathy produces an 84% increase in Vmax and a 35% decrease of KM for 2-oxoglutarate
NH4+
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50 mM NH4Cl, 21% inhibition of the 2-oxoglutarate dehydrogenase complex
reactive oxygen species
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alpha-KGDH can generate reactive oxygen species during its catalytic function, which is regulated by the NADH/NAD+ ratio, formation by alpha-KGDH is attributed to the E3 subunit
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reactive oxygen species
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aconitase in the Krebs cycle is more vulnerable than alpha-KGDH to reactive oxygen species, alpha-KGDH can generate reactive oxygen species during its catalytic function, which is regulated by the NADH/NAD+ ratio, as long as alpha-KGDH is functional NADH generation in the Krebs cycle is maintained
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succinyl phosphonate
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specific inhibitor of cellular KGDHC, 20% inhibition at 0.2 mM
succinyl phosphonate
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potent, slow-binding inhibitor of the 2-oxoglutarate dehydrogenase complex, complete inhibition at 0.1 mM
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specific inhibitor of cellular KGDHC, 44% inhibition at 0.5 mM
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rapid inhibition, 87.7% reduced activity at 0.1 mM, inhibition is blocked by reduced glutathione or cysteine at large molar excess, ascorbate protects partially, inhibition is not affected by catalase and superoxide dismutase
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may play a role in the inhibition of alpha-KGDH during ischemia or reperfusion, is present in elavated concentrations in such cells
Zn2+
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inhibition of the 2-oxoglutarate dehydrogenase complex requires enzyme cycling and is reversed by EDTA. Reversibility is inversely related to the duration of exposure and the concentration of Zn2+. Physiological free Zn2+ may modulate hepatic mitochondrial respiration by reversible inhibition of the 2-oxoglutarate dehydrogenase complex
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ethyl 4-[ethoxy(hydroxy)phosphoryl]-4-oxobutanoate and triethyl esters of succinyl phosphonate are ineffective
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additional information
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inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation
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additional information
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enzyme activity is reduced by 40% in PC12 cells treated with doxycyclin, which is reversible by deprenyl, monoamine oxidase-B-mediated enzyme inhibition, Ca2+ levels influence the NADH/NAD+ pool, which influences the enzyme
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additional information
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the enzyme is targeted for ubiquitination-dependent degradation in mitochondria by binding of Siah2, the RING finger ubiquitin-protein isopeptide ligase 2, encoded by gene siah2
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additional information
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desuccinylation of the enzyme by SIRT5 inhibits the activity of the enzyme complex
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