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
-
-
-
-
oxidative decarboxylation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive carboxylation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
Citrate cycle (TCA cycle)
-
-
L-glutamine biosynthesis III
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
TCA cycle II (plants and fungi)
-
-
TCA cycle III (animals)
-
-
citric acid cycle
-
-
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
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain ON107
SwissProt
Manually annotated by BRENDA team
Landsberg
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
pigeon
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain H37Rv
-
-
Manually annotated by BRENDA team
strain H37Rv
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
W 6
-
-
Manually annotated by BRENDA team
W 6
-
-
Manually annotated by BRENDA team
Sarcophaga barbata
-
-
-
Manually annotated by BRENDA team
gene SlIDH1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
waterbug
-
-
-
Manually annotated by BRENDA team
citrate-overproducing yeast, strain BKM Y-2373
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
ssp. mobiliss
-
-
Manually annotated by BRENDA team
ssp. mobiliss
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
metabolism
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
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
-
the enzyme is also active with NADP+ and NADPH, cf. EC 1.1.1.42
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
-
inhibition with a 50% reduction in activity observed with 40 nM mRNA
-
2-hydroxyethylamine-N,N-diacetate
-
-
2-oxoglutarate
2-Oxopropane-1,1,3-tricarboxylate
-
only in presence of ADP
beta-mercapto-alpha-ketoglutarate
-
inhibition in presence and absence of AMP, competitive inhibition
bilirubin
-
-
Chicago sky blue
-
-
citrate
Congo red
-
-
D,L-hibiscusate
-
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
-
inhibition in presence and absence of AMP, competitive inhibition
D-malate
-
inhibition only in absence of AMP
D-Tartrate
-
inhibition only in absence of AMP
Diamide
EDTA
-
-
EGTA
-
-
fluorescein
-
halogenated derivatives
Fluorocitrate
-
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, fluorocitrate is an activator
fumarate
-
inhibition only in absence of AMP
gamma-aminobutyric acid
-
slight inhibition
glutamate
-
slight inhibition
glyoxylate
homocitrate
-
inhibition only in absence of AMP
L-garciniate
-
inhibition in presence and absence of AMP
-
L-glutamate
-
-
L-hibiscusate
-
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, L-hibiscusate is an activator
-
L-malate
-
inhibition only in absence of AMP, competitive inhibition
L-Tartrate
-
inhibition only in absence of AMP
Maleate
-
inhibition only in absence of AMP
malonate
-
inhibition only in absence of AMP
Mg2+
-
free form
mitochondrial COX2 UTR RNA
-
-
-
molybdate
mRNA
-
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
-
-
oxaloacetate
p-hydroxymercuribenzoate
-
-
pyruvate
-
with oxaloacetate, concomitantly added, less effective than glyoxylate + oxaloacetate
succinate
Succinic semialdehyde
Sulfobromophthalein
-
-
Thiocyanate
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
DTT
-
; 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
-
6fold His-tagged enzyme, at 70C 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 - 4.7
NAD+
0.017 - 8.2
NADP+
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.27 - 73
D-isocitrate
1.5 - 124
DL-isocitrate
13.7
homoisocitrate
Pyrococcus horikoshii
-
6fold His-tagged enzyme, at 70C 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 - 112
NAD+
14 - 168
NADP+
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000004 - 0.00165
DL-isocitrate
849
0.000002 - 1567
NAD+
7
0.000002 - 821
NADP+
10
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
-
mitochondria from green leaves, forward reaction
0.092
-
partially purified enzyme, idh-II mutant
0.096
-
mitochondria from etiolated leaves, forward reaction
0.15
-
enzyme extract of cells in exponential growth phase
0.16
-
enzyme extract of cells in stationary growth phase
0.169
-
partially purified enzyme, wild-type
0.17
-
enzyme extract of cells in growth phase with acid synthesis
0.2
-
D234C, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
1.4
-
D230C, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
2.2
-
purified recombinant mutant gamma-R97Q
2.9
-
-
3.7
-
D215N, gamma-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
13.5
-
purified recombinant mutant beta-R99Q
21.7
-
purified recombinant wild-type enzyme
27 - 31
-
-
29
-
D206N, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
50.5
-
with 0.12 mM NADP+ and 2 mM D-isocitrate
75.5
-
with 0.12 mM NADP+ and 2 mM D-isocitrate
120
purified native enzyme
additional information
-
no activity on 3-isopropylmalate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
-
-
7 - 7.2
-
-
7.2
-
assay at
8.1 - 8.3
-
-
8.1
-
vertebrate muscle
8.4
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8.6
-
-
6 - 8.5
-
-
6 - 8
-
-
6.5 - 8.5
6.5 - 10
-
activity range, profile overview
7.2 - 9.2
-
activity range, profile overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
70
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12 - 37
-
-
25 - 55
-
activity range, profile overview
25 - 60
-
and above, activity range, profile overview
80 - 95
-
activity at 80C is about 50% compared to the activity at 90C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
malignant
Manually annotated by BRENDA team
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multiple
Manually annotated by BRENDA team
At4g35650 is not expressed in vegetative organs but is mainly expressed in the pollen
Manually annotated by BRENDA team
apex; apex; apex; apex
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32850
IDH IV, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
35910
IDH III, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
36040
IDH VI, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
36200
IDH V, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
36340
-
4 * 36340, the clasp-like domain of McIDH is a likely site for tetramerization, calculated from sequence
36810
IDH II, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
37000
-
2 * 37000, 1 * 39000, 1 * 39000
37500
-
IDH2, SDS-PAGE
38900
IDH I, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
39590
IDH II, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
39630
IDH I, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
39960
IDH III, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
40500
-
alpha8, 8 * 40500, SDS PAGE, ICDH-1 and ICDH-2
40580
IDH VI, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
40620
IDH V, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
41000
-
alphabeta, 1 * 39000 + 1 * 41000, SDS-PAGE
44300
-
2 * 44300, calculated from sequence
46000
-
2 * 46000, recombinant His6-tagged enzyme, SDS-PAGE
52000
-
8 * 52000, SDS-PAGE
74000
-
recombinant His6-tagged enzyme, gel filtration
83181
-
3 * 83181, calculated from amino acid sequence
90000
gel filtration and native PAGE
123000
-
disulfide bonded form of subunit IDH2, nonreducing PAGE
145000
-
gel filtration
191800
-
gel filtration
224000
-
ultracentrifugation
238000
-
gel filtration
245000
-
sedimentation equilibrium analysis
250000
-
Superose 6 gel filtration
260000
-
dynamic light scattering
290000
-
Superdex 200 gel filtration
300000 - 340000
-
gel filtration
303000
-
sequence calculation
315000
-
about, recombinant wild-type and mutant enzymes, gel filtration
320000
335000
gel filtration; wild-type enzyme, gel filtration; wild-type enzyme, gel filtration
338000
-
gel filtration
412000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterotetramer
homodimer
monomer
octamer
tetramer
trimer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
-
phosphoprotein
-
catalytically important phosphorylation site at Ser102
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant isocitrate dehydrogenase complexed with NAD+ and citrate solved to a resolution of 1.9 A, hanging drop vapor diffusion method
-
crystallization in artificial mother liquor supplemented with 100 mM NAD+
-
sitting drop vapour diffusion method, using 3-5% (w/v) PEG 20000, 0.1 M MES pH 5.7 and 0.2 M CaCl2
-
hanging drop vapor diffusion method
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8.5
-
-
286757
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0
-
full loss in activity in a few hours
42
-
10 min, 50% loss in activity
50
-
purified recombinant enzyme, inactivation
102
-
the apparent melting temperature is 102.3C, mutant enzyme D328K
103
-
the apparent melting temperature is 102.9C, mutant enzyme D328K/I329Y
additional information
-
thermal denaturation is an irreversible process
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
20 h in medium containing ADP
20% glycerol stabilizes during storage
-
ICDH-2 is more stable to urea than ICDH-1
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, partially purified enzyme, several months, stable
-
-90C, no loss of activity after 6 weeks
4C, glycerol 20%, 35-40% of original activity after 96 h, membrane-associated ICDH
-
4C, recombinant wild-type enzyme, in affinity elution buffer containing 50 mM sodium phosphate, pH 7.5, 300 mM NaCl, and 200 mM imidazole, stable for several weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
129fold to homogeneity by ammonium sulfate fractionation, hydrophobic chromatography on an octyl resin, and gel filtration
-
ammonium sulfate fractionation and gel filtration
-
gel filtration
-
Hi-Trap chelating column chromatography and Superdex 200 gel filtration
-
Hi-Trap chelating HP column chromatography
-
mitochondrial preparation
-
multi-step purification of the native enzyme, 520fold to homogeneity, partial purification of the recombinant enzyme from Escherichia coli
Ni-NTA column chromatography
-
Ni2+-affinity chromatography
Ni2+-nitrilotriacetate (Ni2+-NTA) column chromatography
Ni2+-nitrilotriacetic acid resin chromatography
-
Ni2+-nitrilotriacetic acid superflow resin chromatography
-
partially by mitochondrion isolation in a Percoll gradient, and ammonium sulfate precipitation in the 60-80% fraction, DEAE cellulose chromatography, and desalting
-
recombinant His-tagged enzyme from Escherichia coli strain BL21-Gold(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from strain IDH12DELTAL by nickel affinity chromatography
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21 (DE3)
-
recombinant wild-type and mutant enzymes from Escherichia coli
recombinant wild-type and mutant NAD-IDHs from Escherichia coli by ammonium sulfate fractionation, anion exchange chromatography, ultrafiltration, and gel filtration
-