Information on EC 1.1.1.42 - isocitrate dehydrogenase (NADP+)

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.1.1.42
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RECOMMENDED NAME
GeneOntology No.
isocitrate dehydrogenase (NADP+)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
oxalosuccinate = 2-oxoglutarate + CO2
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidative decarboxylation
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redox reaction
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reductive carboxylation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
ethylene biosynthesis V (engineered)
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L-glutamine biosynthesis III
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methylaspartate cycle
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mixed acid fermentation
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NAD/NADP-NADH/NADPH cytosolic interconversion (yeast)
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partial TCA cycle (obligate autotrophs)
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reductive TCA cycle I
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TCA cycle I (prokaryotic)
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TCA cycle IV (2-oxoglutarate decarboxylase)
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TCA cycle V (2-oxoglutarate:ferredoxin oxidoreductase)
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TCA cycle VII (acetate-producers)
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TCA cycle VIII (helicobacter)
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citric acid cycle
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Citrate cycle (TCA cycle)
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Glutathione metabolism
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Carbon fixation pathways in prokaryotes
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Microbial metabolism in diverse environments
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Biosynthesis of antibiotics
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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
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
from 3 different altitudes of a stream of 700-1920 m, 2 polymorphic isozymes IDHP-A and IDHP-B, isozymes show allelic variants in populations belonging to different living heights in the stream, overview
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
gene NADP-ICDH
UniProt
Manually annotated by BRENDA team
gene NADP-ICDH
UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
and strain 124A
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Manually annotated by BRENDA team
and strain 124A
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
gene Rv3339c
UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Pinus spp.
Scots pine
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Manually annotated by BRENDA team
i.e. Rhodobacter sphaeroides
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Manually annotated by BRENDA team
duck weed, isozymes ICDH1 and ICDH2
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
PCC 6803
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Thermus thermophilus HB8 / ATCC 27634 / DSM 579
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UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Q6C2Y4
UniProt
Manually annotated by BRENDA team
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Q6C2Y4
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2R,3S)-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
(2R,3S)-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
3-fluoroisocitrate + NADP+
3-fluoro-2-oxoglutarate + NADPH + CO2
show the reaction diagram
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?
3-hydroxyisocitrate + NADP+
3-hydroxy-2-oxoglutarate + NADPH + CO2
show the reaction diagram
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?
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
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?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
Ds-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
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?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
isocitrate + NAD+
2-oxoglutarate + NADH + H+
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + CO2
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + H+
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
show the reaction diagram
isocitrate + NADP+
oxalosuccinate + NADPH + H+
show the reaction diagram
isopropylmalate + NADP+
?
show the reaction diagram
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?
oxalosuccinate
2-oxoglutarate + CO2
show the reaction diagram
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r
threo-Ds-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
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?
additional information
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
Q9SRZ6
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?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
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?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + CO2
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + H+
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
show the reaction diagram
isocitrate + NADP+
oxalosuccinate + NADPH + H+
show the reaction diagram
oxalosuccinate
2-oxoglutarate + CO2
show the reaction diagram
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r
additional information
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
activates slightly, 10.18% activity compared to Mn2+
KCl
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the activity of the enzyme is markedly dependent on the concentration of NaCl or KC1 in the Tris/EDTA/Mg2+ buffer, being maximal in 0.5 M NaCl or KCl. The stimulatory effect of KCl is greater than that of NaCl
NaCl
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the activity of the enzyme is markedly dependent on the concentration of NaCl or KC1 in the Tris/EDTA/Mg2+ buffer, being maximal in 0.5 M NaCl or KCl. The stimulatory effect of KCl is greater than that of NaCl
Rb+
activates slightly, 20.67% activity compared to Mn2+
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(+)-ML309
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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
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(-)-ML309
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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
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2',5'-ADP
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2,3-Butanedione
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2-mercaptoethanol
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2-oxoglutarate
3-morpholinosydnonimine
44% inhibition at 5 mM of leaf and root enzymes
3-phosphoglycerate
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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
5'-ADP
adenosine-3',5'-cyclic monophosphate
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cis-aconitate
citrate
Citric acid
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50% inhibition at 1 mM
desferroxamine
Diamide
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Diethylenetriaminepentaacetic acid
Diphenylchloroarsine
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dithiothreitol
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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
glutamate
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80% inhibition of isozyme ICDH2 at 2 mM
glutathione
glutathione disulfide
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incubation with 5 mM glutathione disulfide for 30 min completely eliminates activity
glyceraldehyde-3-phosphate
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glyoxalate
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20% inhibition at 1 mM, presence of 1 mM oxaloacetate results in 50% inhibition
glyoxylate
GSH
inhibits the leaf enzyme by 40% at 5 mM, but not the root enzyme
GTP
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10% inhibition at 1 mM
isocitrate
Itaconate
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18% inhibition at 5 mM
Li+
slight inhibition
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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malate
noncompetitive versus NADP+ and isocitrate