1.1.1.42: isocitrate dehydrogenase (NADP+)
This is an abbreviated version!
For detailed information about isocitrate dehydrogenase (NADP+), go to the full flat file.
Word Map on EC 1.1.1.42
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1.1.1.42
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glioma
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glioblastoma
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astrocytomas
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dehydrogenases
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malate
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leukemia
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myeloid
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glucose-6-phosphate
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resect
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oncometabolite
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oligodendrogliomas
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d-2-hydroxyglutarate
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anaplastic
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malic
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idh1-mutant
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tricarboxylic
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hypermethylation
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multiforme
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high-grade
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progression-free
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temozolomide
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2-oxoglutarate
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radiotherapy
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codeletion
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neomorphic
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alpha-ketoglutarate
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6-phosphogluconate
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nadph-generating
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cholangiocarcinomas
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o6-methylguanine-dna
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gliomagenesis
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aconitase
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oligodendroglial
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lgg
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chondrosarcoma
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lower-grade
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oligoastrocytomas
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medicine
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nadp-malic
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supratentorial
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biotechnology
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nadph-producing
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analysis
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diagnostics
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nadp-me
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radiomics
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pilocytic
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karnofsky
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proneural
- 1.1.1.42
- glioma
- glioblastoma
- astrocytomas
- dehydrogenases
- malate
- leukemia
- myeloid
- glucose-6-phosphate
-
resect
-
oncometabolite
- oligodendrogliomas
- d-2-hydroxyglutarate
-
anaplastic
-
malic
-
idh1-mutant
-
tricarboxylic
-
hypermethylation
- multiforme
-
high-grade
-
progression-free
- temozolomide
- 2-oxoglutarate
-
radiotherapy
-
codeletion
-
neomorphic
- alpha-ketoglutarate
- 6-phosphogluconate
-
nadph-generating
- cholangiocarcinomas
-
o6-methylguanine-dna
-
gliomagenesis
- aconitase
-
oligodendroglial
- lgg
- chondrosarcoma
-
lower-grade
- oligoastrocytomas
- medicine
-
nadp-malic
-
supratentorial
- biotechnology
-
nadph-producing
- analysis
- diagnostics
- nadp-me
-
radiomics
-
pilocytic
-
karnofsky
-
proneural
Reaction
Synonyms
AbIDH1, AfIDH, CgIDH, cICDH, CtIDP1, CtIDP2, cytosolic isocitrate dehydrogenase 1, cytosolic NADP(+)-dependent isocitrate dehydrogenase, cytosolic NADP+-dependent isocitrate dehydrogenase, cytosolic NADP-dependent isocitrate dehydrogenase, cytosolic NADPH-dependent isocitrate dehydrogenase, DpIDH, EcIDH, HICDH, ICD, ICD1, ICD2, icdA, ICDH, ICDH-1, IDH, IDH-90, IDH-I, IDH-IIa, IDH-IIb, IDH1, IDH2, IDH3, IDHP, IDP, IDP1, IDP2, IDP3, IDPA, IDPc, IDPm, isocitrate dehydrogenase, isocitrate dehydrogenase (NADP), isocitrate dehydrogenase (NADP-dependent), isocitrate dehydrogenase (nicotinamide adenine dinucleotide phosphate), isocitrate dehydrogenase 1, isocitrate dehydrogenase 2, isocitrate dehydrogenase-1, isocytrate deyhdrogenase, mICDH, mitochondrial NADP+-dependent isocitrate dehydrogenase, NAD+-dependent isocitrate dehydrogenase, NADP isocitric dehydrogenase, NADP+ dependent isocitrate dehydrogenase, NADP+-dependent Ds-threo-isocitrate dehydrogenase, NADP+-dependent Ds-threo-isocitrate:NADP+ oxidoreductase, NADP+-dependent ICDH, NADP+-dependent IDH, NADP+-dependent isocitrate dehydrogenase, NADP+-ICDH, NADP+-IDH, NADP+-isocitrate dehydrogenase, NADP+-linked isocitrate dehydrogenase, NADP+-specific ICDH, NADP+-specific IDH, NADP+-specific isocitrate dehydrogenase, NADP-dependent IDH, NADP-dependent isocitrate dehydrogenase, NADP-dependent isocitric dehydrogenase, NADP-ICDH, NADP-IDH, NADP-IDH Idp1p, NADP-isocitrate dehydrogenase, NADP-linked isocitrate dehydrogenase, NADP-specific isocitrate dehydrogenase, NADPH-dependent isocitrate dehydrogenase, NADPH-IDH, oxalosuccinate decarboxylase, oxalsuccinic decarboxylase, perICDH, PS-NADP-IDH, TaIDH, TM1148, YlIDP
ECTree
1.1.1.42 isocitrate dehydrogenase (NADP+)Advanced search results
results (
results (Inhibitors
Inhibitors on EC 1.1.1.42 - isocitrate dehydrogenase (NADP+)
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(+)-ML309
reversible binding analysis and mechanism, detailed overview. The reversible inhibitor binds to IDH1 R132H competitively with respect to 2-oxoglutarate and uncompetitively with respect to NADPH. ML309 competes with 2-oxoglutarate but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-hydroxyglutarate levels. The rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active, whereas the (-) isomer is over 400fold less active for IDH1 R132H inhibition. IDH1 R132C is similarly inhibited by (-)-ML309. ML309 is also able to inhibit 2-hydroxyglutarate production in a glioblastoma cell line and had minimal cytotoxicity. In the presence of racemic ML309, 2-hydroxyglutarate levels drop rapidly
(-)-ML309
reversible binding analysis and mechanism, detailed overview. The reversible inhibitor binds to IDH1 R132H competitively with respect to 2-oxoglutarate and uncompetitively with respect to NADPH. ML309 competes with 2-oxoglutarate but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-hydroxyglutarate levels. The rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active, whereas the (-) isomer is over 400fold less active for IDH1 R132H inhibition. IDH1 R132C is similarly inhibited by (-)-ML309. Wild-type IDH1 is largely unaffected by (+)-ML309. ML309 is also able to inhibit 2-hydroxyglutarate production in a glioblastoma cell line and had minimal cytotoxicity. In the presence of racemic ML309, 2-hydroxyglutarate levels drop rapidly
(5aS,6S,9aR)-2-benzoyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile
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(5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile
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(6aS,7S,10aR)-2-anilino-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
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(6aS,7S,10aR)-7,10a-dimethyl-8-oxo-2-(phenylamino)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
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(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-[(pyridin-3-yl)amino]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
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(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
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(6aS,7S,10aS)-2-anilino-7-methyl-10a-phenyl-5,6a,7,10a-tetrahydrobenzo[h]quinazolin-8(6H)-one
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(7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1R)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide
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3-morpholinosydnonimine
44% inhibition at 5 mM of leaf and root enzymes
3-[(5aS,6S,9aR)-8-cyano-6-methyl-7-oxo-2,4,5,5a,6,7-hexahydro-9aH-benzo[g]indazol-9a-yl]benzoic acid
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3-[(6aS,7S,10aR)-2-anilino-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid
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4-hydroxynonenal
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50% inhibition at 37°C, after 1 h at 0.5 mM, lipid peroxidation product, enzyme becomes susceptible to oxidative damage leading to structural alterations, carbonylation
Fe2+
the inhibitory effect of the Fe2+ and H2O2 mixture associated with the generation of hydroxyl radicals is lower in enzyme from ischemic heart compared to enzyme from normoxic heart
glutathione disulfide
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incubation with 5 mM glutathione disulfide for 30 min completely eliminates activity
glyoxalate
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20% inhibition at 1 mM, presence of 1 mM oxaloacetate results in 50% inhibition
GSH
inhibits the leaf enzyme by 40% at 5 mM, but not the root enzyme
GSSG
increasing GSSG concentrations progressively inhibit the enzyme activity, almost complete inhibition at 1 mM
lipid hydroperoxide
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50% inhibition at 37°C, after 1 h at 0.05 mM, lipid peroxidation product, enzyme becomes susceptible to oxidative damage leading to structural alterations, carbonylation
liposome
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ICDH activity is enhanced with liposomes at 5 mol% cardiolipin, but inhibited at 30 mol% cardiolipin. 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine liposomes do not affect the activity of ICDH
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malondialdehyde
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50% inhibition at 37°C, after 1 h at 5 mM, lipid peroxidation product, enzyme becomes susceptible to oxidative damage leading to structural alterations, carbonylation
Mn2+
the specific activity of purified enzyme is increased by Mn2+ in the micromolar range
NaCl
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isoform ICD-2, increase in activity in up to 200 mM NaCl. Isoform ICD-1, no influence of NaCl. Above 200 mM, NaCl is inhibitory
NaHS
2 and 10 mM NaHS used as H2S donors result in a decrease in enzyme activity of up to 36% and 45%, respectively
nitrosoglutathione
increasing nitrosoglutathione concentrations progressively inhibit the enzyme activity, complete inhibition at 2 mM
S-nitrosoglutathione
70.5% inhibition at 5 mM of the leaf enzyme, 37.3% of the root enzyme
2-oxoglutarate
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50% inhibition of the forward reaction at 1.5 mM, 99% inhibition at 15 mM
2-oxoglutarate
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50% inhibition of the forward reaction at 1.5 mM, 95% inhibition at 15 mM
2-oxoglutarate
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isozymes ICDH2 and ICDH1, isozyme ICDH2 is more sensitive to negative feedback inhibition by 2-oxoglutarate
Ca2+
in the presence of Mn2+, Ca2+ strongly inhibits the activity of the enzyme (28.52% residual activity)
Cd2+
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inhibits the purified enzyme and the enzyme in cells, NADP+ does not protect. No inhibition of IDPc mutant S269S. DNA fragmentation is enhanced in IDPc siRNA-transfected HEK293 cells compared to control cells upon exposure to cadmium
Cd2+
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coadministration with oxalomalate results in inhibition of enzyme and glutaredoxin and enhanced susceptibility to apoptosis
Cd2+
above 0.1 mM, the enzyme loses activity, and at 2 mM Cd2+ most of the activity has disappeared. Chelation of Cd2+ by dithiothreitol cannot recover the lost enzyme activity. Inactivation of the enzyme by Cd2+ is less effective when the enzyme is activated with Cd2+ than Mg2+, More than 50% of the activity of the enzyme activated with 0.05 mM Cd2+ remains in the presence of 1 mM GSH
Cd2+
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binds to C379 of enzyme, resulting in loss of activity and structural alterations. Loss of glutaredoxin activity in cells treated with Cd2+ is more pronounced when cells are transfected with enzyme antisense cDNA
Cu2+
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enzyme is completely inhibited at 5 mM in presence of 5 mM Mg2+, organism is a copper-tolerant basidiomycete
glutathione
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oxidized glutathione leads to enzyme inactivation with simultaneous formation of a mixed disulfide between glutathione and the cysteine residues of enzyme. Enzymical reactivation by glutaredoxin2 in presence of reduced glutathione
glyoxylate
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18% inhibition at 5 mM, mixed type inhibition together with oxaloacetate, completely at 5 mM each
H2O2
affects the root enzyme slightly but not the enzyme from leaves
H2O2
the inhibitory effect of the Fe2+ and H2O2 mixture associated with the generation of hydroxyl radicals is lower in enzyme from ischemic heart compared to enzyme from normoxic heart
HOCl
i.e. hypochlorous acid, the HOCl-mediated damage to NADP+-dependent isocitrate dehydrogenase mayesult in perturbation of the cellular antioxidant defense mechanism and subsequently lead to a pro-oxidant condition
isocitrate
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50% inhibition of the reverse reaction at 0.1 mM, 97% inhibition at 1.2 mM
isocitrate
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70% inhibition of the reverse reaction at 0.1 mM, 99% inhibition at 1.2 mM
manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
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a superoxide dismutase mimic, ICD is inactivated by superoxide, but the inactivated enzyme is replaced by de novo protein synthesis
manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
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a superoxide dismutase mimic
NADPH
product inhibition competitive versus NADP+ and noncompetitive versus isocitrate
oxaloacetate
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competitive, inhibits the reverse reaction, over 50% inhibition at 1 mM, synergistically with glyoxylate
oxaloacetate
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41% inhibition at 5 mM, mixed type inhibition together with glyoxylate, completely at 5 mM each
oxaloacetate
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25% inhibition at 1 mM, presence of 1 mM glyoxalate results in 50% inhibition
Oxalomalate
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competitive, coadministration with CD2+ results in inhibition of enzyme and glutaredoxin and enhanced susceptibility to apoptosis
peroxynitrite
causes a 26% inhibition in enzyme activity with 5 mM SIN-1
peroxynitrite
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ethanol toxicity is mediated by peroxynitrite and the peroxynitrite-mediated damage to NADP+-dependent isocitrate dehydrogenase and superoxide dismutase may be resulting in the perturbation of the cellular antioxidant defense systems and subsequently lead to a pro-oxidant condition
phosphoenolpyruvate
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allosteric inhibition. Phosphoenolpyruvate enhances the uncompetitive inhibition of isocitrate lyase by increasing isocitrate, which protects isocitrate dehydrogenase from the inhibition, and contributes to the control through the tricarboxylic acid cycle and glyoxylate shunt
Zn2+
in the presence of Mn2+, Zn2+ strongly inhibits the activity of the enzyme (42.59% residual activity)
additional information
increasing concentrations of H2O2 hardly affect the enzyme activity
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additional information
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increasing concentrations of H2O2 hardly affect the enzyme activity
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additional information
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no inhibition of carboxylation by citrate, pyruvate, succinate, fumarate, malate, glyoxylate, ATP, and ADP
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additional information
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AMP is a no inhibitor, no inhibition by glutamate, pyruvate and succinate
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additional information
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transfection of HeLa cells with an IDPc small interfering RNA decreases activity of IDPc by 80%, enhancing the susceptibility of staurosporine-induced apoptosis reflected by DNA fragmentation, cellular redox status and the modulation of apoptotic marker proteins
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additional information
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5 mM glutathione does not noticeably inhibit IDPc activity
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additional information
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tumor-derived mutant IDH1 dominantly inhibits the wild-type IDH1 by forming a catalytically inactive heterodimer, resulting in a decrease of cellular 2-oxoglutarate
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additional information
the enzyme is unaffected by the addition of 5 mM L-glutamate, L-glutamine, 2-oxoglutarate, oxaloacetate, cis-aconitate, citrate, pyruvate, malate, fumarate, succinate, CoA, AcCoA, NADH, and NADPH or 2 mM ADP and AMP
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additional information
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ischemia-reperfusion significantly reduces IDPc expression and activity
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additional information
ischemia-reperfusion reduces IDH2 expression and activity in both Idh2+/+ and Idh2-/- kidneys
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additional information
product inhibition patterns for ICDH-1, overview
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additional information
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product inhibition patterns for ICDH-1, overview
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additional information
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poor inhibition of the forward reaction by 2-oxoglutarate, no inhibition by CO2
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additional information
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enzyme is not affected by gamma-aminobutyric acid and succinate
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additional information
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activity is not affected by the nonspecific binding of the mitochondrial isozyme, not the cytosolic one, to 5'-untranslated regions of yeast mitochondrial mRNAs
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additional information
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no inhibition by phosphoenolpyruvate, fructose 1,6-bisphosphate, and pyruvate
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