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Information on EC 1.1.1.42 - isocitrate dehydrogenase (NADP+) and Organism(s) Rattus norvegicus and UniProt Accession P56574

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IUBMB Comments
Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+), oxalosuccinate can be used as a substrate. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP+-linked enzyme that is found in both mitochondria and cytoplasm . The enzyme from some species can also use NAD+ but much more slowly [6,7].
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This record set is specific for:
Rattus norvegicus
UNIPROT: P56574
Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
isocitrate dehydrogenase 1, nadp-isocitrate dehydrogenase, nadp-dependent isocitrate dehydrogenase, nadp-icdh, nadp-idh, isocitrate dehydrogenase-1, nadp-linked isocitrate dehydrogenase, nadp+-dependent isocitrate dehydrogenase, nadp-specific isocitrate dehydrogenase, nadp+-specific isocitrate dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cICDH
276034
-
CtIDP1
-
-
-
0
CtIDP2
-
-
-
0
ICDH
276034
-
IDH
-
-
-
0
IDP
-
-
-
0
IDPm
283908
-
isocitrate dehydrogenase (NADP)
-
-
-
0
isocitrate dehydrogenase (NADP-dependent)
-
-
-
0
isocitrate dehydrogenase (nicotinamide adenine dinucleotide phosphate)
-
-
-
0
mICDH
276034
-
NADP isocitric dehydrogenase
-
-
-
0
NADP+-dependent isocitrate dehydrogenase
NADP+-linked isocitrate dehydrogenase
-
-
-
0
NADP+-specific ICDH
-
-
-
0
NADP-dependent isocitrate dehydrogenase
NADP-dependent isocitric dehydrogenase
-
-
-
0
NADP-ICDH
283908
-
NADP-isocitrate dehydrogenase
283908
-
NADP-linked isocitrate dehydrogenase
-
-
-
0
NADP-specific isocitrate dehydrogenase
-
-
-
0
oxalosuccinate decarboxylase
-
-
-
0
oxalsuccinic decarboxylase
-
-
-
0
PS-NADP-IDH
-
-
-
0
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
0
oxidative decarboxylation
-
-
-
0
reductive carboxylation
-
-
-
0
SYSTEMATIC NAME
IUBMB Comments
isocitrate:NADP+ oxidoreductase (decarboxylating)
Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+), oxalosuccinate can be used as a substrate. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP+-linked enzyme that is found in both mitochondria and cytoplasm [6]. The enzyme from some species can also use NAD+ but much more slowly [6,7].
CAS REGISTRY NUMBER
COMMENTARY hide
9028-48-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
r
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-
isocitrate dehydrogenase is an important NADPH-generating enzyme in the endoplasmic reticulum
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
Km-value: 0.42 mM for enzyme from normoxic heart, 0.15 mM for enzyme from ischemic heart
Mg2+
-
absolute requirement for divalent cations
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-oxoglutarate
-
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
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
2-oxoglutarate
-
desferroxamine
-
-
Diethylenetriaminepentaacetic acid
-
-
manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
-
a superoxide dismutase mimic
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017 - 0.045
isocitrate
0.046
NADP+
0.017 - 0.045
DL-isocitrate
0.046
NADP+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.08 - 0.25
2-oxoglutarate
0.159 - 0.28
citrate
0.05
Fe2+
0.15
glutathione
pH 7.8, 25°C, enzyme from normoxic heart
0.45 - 1.63
H2O2
0.08 - 0.25
2-oxoglutarate
0.159 - 0.28
citrate
0.05
Fe2+
0.15
glutathione
enzyme from normoxic heart, pH 7.8, 25°C
0.45 - 1.63
H2O2
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
enzyme from ischemic heart
50
enzyme from normoxic heart
22
assay at room temperature
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 50
25°C: about 50% of maximal activity, 50°C: about 70% of maximal activity, enzyme from ischemic heart
35 - 70
35°C: about 45% of maximal activity, 70°C: about 60% of maximal activity, enzyme from normoxic heart
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
pancreatic islet beta-cell, suppression of enzyme activity by small interfering RNA results in impairment of glucose-stimulated insulin secretion, attenuates glucose-induced increments in pyruvate cycling activity and in NADPH levels, and causes increases in lactate production
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
86% of total activity in the cell, main factor for synthesis of 2-oxoglutarate. Enzyme and cytoplasmic aspartate aminotransferase are regulated oppositely and the catalytic activity of one enzyme can be stimulated concurrently with a decrease in the activity of the other
Manually annotated by BRENDA team
-
isozyme ICD1, minor appearance
Manually annotated by BRENDA team
-
isoyzme ICD2
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
transfection of H9c2 clonal myoblastic cells with small interfering RNA (siRNA) specific for IDPm markedly attenuates IDPm expression and substantially induces apoptosis, senescence, and hypertrophy as indicated by increased atrial natriuretic peptide gene expression, a marker of cardiomyocyte hypertrophy, and a larger cell size. Knockdown of IDPm expression results in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. The suppression of IDP expression by siRNA induces apoptosis and hypertrophy of cultured cardiomyocytes through the disruption of cellular redox balance. IDPm knockdown alters cellular redox status and induces oxidative damage. Apoptosis induced by IDPm knockdown is ROS-mediated. Substantially increased desmin and vimentin abundance is observed in IDPm siRNA-transfected H9c2 cells compared to the control cells. Mitochondrial fission and fusion involve enzymatic reactions mediated by large dynamin-associated GTPases. IDPm knockdown induces mitochondrial damage by altering the redox status
physiological function
mitochondrial NADP+s-dependent isocitrate dehydrogenase (IDPm) functions as an antioxidant and antiapoptotic protein by supplying NADPH to antioxidant systems
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
IDHP_RAT
452
0
50967
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45000
-
x * 45000, isozyme ICD1, SDS-PAGE
47000
x * 47000, approximately, cytosolic and mitochondrial isozymes, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
knockdown of IDPm by siRNA in H9c2 cells, the suppression of IDPm expression by siRNA induces apoptosis and hypertrophy of cultured cardiomyocytes through the disruption of cellular redox balance, phenotype, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
NADP-isocitrate dehydrogenase from the normoxic and ischemic rat myocardium
native isozymes, partially
partially, isozyme ICD1
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene of mitochondrial isozyme, DNA and amino acid sequence determination and analysis, subcellular RT-PCR analysis of brain cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sechi, S.; Parmalee, D.; Roller, P.P.; Jennings, G.T.
Structural characterization of cytosolic NADP(+)-dependent isocitrate dehydrogenase from rat ovary
Enzyme Protein
48
27-36
1994
Rattus norvegicus
Manually annotated by BRENDA team
Haraguchi, C.M.; Mabuchi, T.; Yokota, S.
Localization of a mitochondrial type of NADP-dependent isocitrate dehydrogenase in kidney and heart of rat: an immunocytochemical and biochemical study
J. Histochem. Cytochem.
51
215-226
2003
Rattus norvegicus
Manually annotated by BRENDA team
Minich, T.; Yokota, S.; Dringen, R.
Cytosolic and mitochondrial isoforms of NADP+-dependent isocitrate dehydrogenases are expressed in cultured rat neurons, astrocytes, oligodendrocytes and microglial cells
J. Neurochem.
86
605-614
2003
Rattus norvegicus (P41562)
Manually annotated by BRENDA team
Rakhmanova, T.I.; Popova, T.N.
Regulation of 2-oxoglutarate metabolism in rat liver by NADP-isocitrate dehydrogenase and aspartate aminotransferase
Biochemistry (Moscow)
71
211-217
2006
Rattus norvegicus
Manually annotated by BRENDA team
Ronnebaum, S.M.; Ilkayeva, O.; Burgess, S.C.; Joseph, J.W.; Lu, D.; Stevens, R.D.; Becker, T.C.; Sherry, A.D.; Newgard, C.B.; Jensen, M.V.
A pyruvate cycling pathway involving cytosolic NADP-dependent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion
J. Biol. Chem.
281
30593-30602
2006
Rattus norvegicus (P41562)
Manually annotated by BRENDA team
Popova, T.; Carvalho, M.A.; Matasova, L.; Medvedeva, L.
Regulation of mitochondrial NADP-isocitrate dehydrogenase in rat heart during ischemia
Mol. Cell. Biochem.
294
97-105
2006
Rattus norvegicus, Rattus norvegicus (P56574)
Manually annotated by BRENDA team
Margittai, E.; Banhegyi, G.
Isocitrate dehydrogenase: A NADPH-generating enzyme in the lumen of the endoplasmic reticulum
Arch. Biochem. Biophys.
471
184-190
2008
Rattus norvegicus
Manually annotated by BRENDA team
Batinic-Haberle, I.; Benov, L.T.
An SOD mimic protects NADP+-dependent isocitrate dehydrogenase against oxidative inactivation
Free Radic. Res.
42
618-624
2008
Escherichia coli, Rattus norvegicus
Manually annotated by BRENDA team
Lee, J.H.; Park, J.W.
Attenuated mitochondrial NADP+-dependent isocitrate dehydrogenase activity induces apoptosis and hypertrophy of H9c2 cardiomyocytes
Biochimie
99
110-118
2014
Rattus norvegicus (P56574)
Manually annotated by BRENDA team
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