Information on EC 1.1.1.41 - isocitrate dehydrogenase (NAD+)

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY hide
1.1.1.41
-
RECOMMENDED NAME
GeneOntology No.
isocitrate dehydrogenase (NAD+)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
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oxidative decarboxylation
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-
-
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redox reaction
-
-
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reduction
-
-
-
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reductive carboxylation
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
citric acid cycle
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Citrate cycle (TCA cycle)
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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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TCA cycle II (plants and fungi)
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TCA cycle III (animals)
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L-glutamine biosynthesis III
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SYSTEMATIC NAME
IUBMB Comments
isocitrate:NAD+ oxidoreductase (decarboxylating)
Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.42, isocitrate dehydrogenase (NADP+), oxalosuccinate cannot 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 [7]. The enzyme from some species can also use NADP+ but much more slowly [9].
CAS REGISTRY NUMBER
COMMENTARY hide
9001-58-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain ON107
SwissProt
Manually annotated by BRENDA team
Landsberg
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
pigeon
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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
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UniProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
strain H37Rv
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-
Manually annotated by BRENDA team
strain H37Rv
-
-
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
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
W 6
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-
Manually annotated by BRENDA team
W 6
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-
Manually annotated by BRENDA team
Sarcophaga barbata
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-
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Manually annotated by BRENDA team
gene SlIDH1
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
waterbug
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-
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Manually annotated by BRENDA team
citrate-overproducing yeast, strain BKM Y-2373
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
ssp. mobiliss
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Manually annotated by BRENDA team
ssp. mobiliss
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-
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
8-(4-bromo-2,3-dioxobutylthio)-NAD+ + isocitrate
2-oxoglutarate + CO2 + 8-(4-bromo-2,3-dioxobutylthio)-NADH
show the reaction diagram
-
-
-
-
?
D-homoisocitrate + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-
very low activity
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
threo-Ds-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
additional information
?
-
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 + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
threo-Ds-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Rb+
activates, 11.0% activity compared to Mg2+ for OlIDH
Zn2+
-
less effective than Mn2+ or Mg2+
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
130-nucleotide transcript containing the 5'-untranslated regions of the yeast mitochondrial COX2 mRNA
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inhibition with a 50% reduction in activity observed with 40 nM mRNA
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2-hydroxyethylamine-N,N-diacetate
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2-oxoglutarate
2-Oxopropane-1,1,3-tricarboxylate
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only in presence of ADP
beta-mercapto-alpha-ketoglutarate
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inhibition in presence and absence of AMP, competitive inhibition
bilirubin
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Chicago sky blue
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-
citrate
Congo red
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D,L-hibiscusate
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with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, D,L-hibiscusate is an activator
D,L-threo-alpha-methylisocitrate
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inhibition in presence and absence of AMP, competitive inhibition
D-malate
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inhibition only in absence of AMP
D-Tartrate
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inhibition only in absence of AMP
Diamide
EDTA
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EGTA
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fluorescein
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halogenated derivatives
Fluorocitrate
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with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, fluorocitrate is an activator
fumarate
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inhibition only in absence of AMP
gamma-aminobutyric acid
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slight inhibition
glutamate
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slight inhibition
glyoxylate
homocitrate
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inhibition only in absence of AMP
L-garciniate
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inhibition in presence and absence of AMP
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L-glutamate
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L-hibiscusate
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with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, L-hibiscusate is an activator
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L-malate
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inhibition only in absence of AMP, competitive inhibition
L-Tartrate
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inhibition only in absence of AMP
Maleate
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inhibition only in absence of AMP
malonate
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inhibition only in absence of AMP
Mg2+
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free form
mitochondrial COX2 UTR RNA
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molybdate
mRNA
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enzyme specifically binds to 5'-untranslated regions of yeast mitochondrial mRNAs, and transcripts containing these regions allosterically inhibit the enzyme, which can be relieved by activator AMP in presence of isocitrate, complex formation, overview
NADPH
nitrilotriacetate
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oxaloacetate
p-hydroxymercuribenzoate
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pyruvate
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with oxaloacetate, concomitantly added, less effective than glyoxylate + oxaloacetate
succinate
Succinic semialdehyde
Sulfobromophthalein
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Thiocyanate
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tributyltin
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TBT, active in NT2/D1 carcinoma cells, overview. At nanomoler concentrations, tributyltin actions are mediated by genomic pathways via peroxisome proliferator-activated receptor gamma/retinoid X receptor, PPAR/RXR. Binding and in silico docking simulation analysis, overview
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
DTT
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; decreases disulfide content of the enzyme, kinetics of enzyme mutants in presence or absence of DTT, overview
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03 - 0.45
D,L-isocitrate
0.09 - 62.2
D-isocitrate
0.075 - 0.385
DL-isocitrate
0.0183
homoisocitrate
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6fold His-tagged enzyme, at 70°C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2, 1mM NAD+
0.0164 - 41
isocitrate
0.22 - 0.39
Mn2+
0.004 - 20.65
NAD+
0.0082 - 8.2
NADP+
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.27 - 73
D-isocitrate
1.5 - 124
DL-isocitrate
13.7
homoisocitrate
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6fold His-tagged enzyme, at 70°C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2, 1 mM NAD+
0.27 - 36.8
isocitrate
0.27 - 115
NAD+
1.4 - 168
NADP+
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000004 - 0.00165
DL-isocitrate
0.000002 - 1567
NAD+
0.000002 - 836
NADP+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.063 - 0.18
NADH
0.26
NADPH
-
pH 7.5
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.084
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mitochondria from green leaves, forward reaction
0.092
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partially purified enzyme, idh-II mutant
0.096
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mitochondria from etiolated leaves, forward reaction
0.15
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enzyme extract of cells in exponential growth phase
0.16
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enzyme extract of cells in stationary growth phase
0.169
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partially purified enzyme, wild-type
0.17
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enzyme extract of cells in growth phase with acid synthesis
0.2
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D234C, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
1.4
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D230C, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
2.2
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purified recombinant mutant gamma-R97Q
2.9
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-
3.7
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D215N, gamma-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
3.8
purified recombinant His6-tagged enzyme, pH 7.5, 25°C, with NADP+
8.7
purified recombinant His6-tagged enzyme, pH 7.5, 25°C, with NADP+
13.5
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purified recombinant mutant beta-R99Q
21.7
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purified recombinant wild-type enzyme
27 - 31
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29
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D206N, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
50.5
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with 0.12 mM NADP+ and 2 mM D-isocitrate
53.2
purified recombinant His6-tagged enzyme, pH 7.5, 25°C, with NAD+
72.3
purified recombinant His6-tagged enzyme, pH 7.5, 25°C, with NAD+
75.5
-
with 0.12 mM NADP+ and 2 mM D-isocitrate
120
purified native enzyme
additional information
-
no activity on 3-isopropylmalate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8.6
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6 - 8.5
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6 - 8
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6.5 - 8.5
6.5 - 10
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activity range, profile overview
7.2 - 9.2
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activity range, profile overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
70
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assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12 - 37
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20 - 32
activity range, profile overview
25 - 55
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activity range, profile overview
25 - 60
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and above, activity range, profile overview
80 - 95
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activity at 80°C is about 50% compared to the activity at 90°C