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Information on EC 4.2.1.3 - aconitate hydratase and Organism(s) Rattus norvegicus and UniProt Accession Q9ER34
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4.2.1.3 aconitate hydrataseIUBMB Comments
Besides interconverting citrate and cis-aconitate, it also interconverts cis-aconitate with isocitrate and, hence, interconverts citrate and isocitrate. The equilibrium mixture is 91% citrate, 6% isocitrate and 3% aconitate. cis-Aconitate is used to designate the isomer (Z)-prop-1-ene-1,2,3-tricarboxylate. An iron-sulfur protein, containing a [4Fe-4S] cluster to which the substrate binds.
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- 4.2.1.3
-
iron-sulfur
- transferrin
-
tricarboxylic
- dismutase
- fe-s
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- tca
- malate
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citric
- cardiac
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rna-binding
- neurodegenerative
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krebs
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iron-dependent
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-
stem-loops
- fluorocitrate
-
bioenergetics
-
ferroportin
-
county
- hepcidin
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- mnsod
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-
georgia
-
cluster-containing
-
iron-deficient
- iscu
-
iron-replete
-
iron-induced
-
iron-mediated
- alabama
-
kennedy
-
itaconic
-
ferrochelatase
- cubane
-
desulfurase
-
nadp-isocitrate
-
rna-protein
-
iron-related
-
soxrs
- l-ferritin
- isopropylmalate
- medicine
- environmental protection
- synthesis
- biotechnology
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
aconitase, iron regulatory protein, irp-1, ire-bp, macon, iron regulatory protein 1, aconitate hydratase, cytoplasmic aconitase, aconitase a, c-aconitase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aconitase
Aconitate hydratase
cis-aconitase
-
-
-
-
citrate hydro-lyase
-
-
-
-
Ferritin repressor protein
-
-
-
-
hydratase, aconitate
-
-
-
-
IP210
-
-
-
-
IRE-BP
-
-
-
-
Iron regulatory protein
-
-
-
-
iron-responsive element binding protein
-
-
-
-
IRP
-
-
-
-
IRP1
Major iron-containing protein
-
-
-
-
MICP
-
-
-
-
aconitase
-
-
-
-
Aconitate hydratase
-
-
-
-
IRP1
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
citrate(isocitrate) hydro-lyase (cis-aconitate-forming)
Besides interconverting citrate and cis-aconitate, it also interconverts cis-aconitate with isocitrate and, hence, interconverts citrate and isocitrate. The equilibrium mixture is 91% citrate, 6% isocitrate and 3% aconitate. cis-Aconitate is used to designate the isomer (Z)-prop-1-ene-1,2,3-tricarboxylate. An iron-sulfur protein, containing a [4Fe-4S] cluster to which the substrate binds.
CAS REGISTRY NUMBER
COMMENTARY
9024-25-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
regulation of mitochondrial aconitase activity by protein kinase C-dependent phosphorylation, augmented phosphorylation of mitochondrial aconitase in diabetic hearts is associated with an increase in its reverse activity, converting isocitrate to aconitate, while the rate of the forward activity is unchanged, overview
-
-
?
additional information
?
-
-
Mn2+ exposure leads to a region-specific alteration in total aconitase: 48.5% reduction of the enzyme activity in frontal cortex, 33.7% in striatum and 20.6% in substantia nigra. This leads to the disruption of mitochondrial energy production and cellular Fe metabolism in the brain
-
-
?
additional information
?
-
-
the enzyme is involved in the assimilation of Fe and excess dietary Zn can result in negative interactions
-
-
?
additional information
?
-
-
effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia, overview
-
-
?
additional information
?
-
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
-
IRP shows RNA-binding activity, which is affected by some hormones and growth factors, e.g. thyroid, erythropoietin, and epidermal growth factor
-
-
?
additional information
?
-
IRP shows RNA-binding activity, which is affected by some hormones and growth factors, e.g. thyroid, erythropoietin, and epidermal growth factor
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
regulation of mitochondrial aconitase activity by protein kinase C-dependent phosphorylation, augmented phosphorylation of mitochondrial aconitase in diabetic hearts is associated with an increase in its reverse activity, converting isocitrate to aconitate, while the rate of the forward activity is unchanged, overview
-
-
?
additional information
?
-
-
Mn2+ exposure leads to a region-specific alteration in total aconitase: 48.5% reduction of the enzyme activity in frontal cortex, 33.7% in striatum and 20.6% in substantia nigra. This leads to the disruption of mitochondrial energy production and cellular Fe metabolism in the brain
-
-
?
additional information
?
-
-
the enzyme is involved in the assimilation of Fe and excess dietary Zn can result in negative interactions
-
-
?
additional information
?
-
-
effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia, overview
-
-
?
additional information
?
-
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
additional information
?
-
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
additional information
Fe2+
required, binding structure in the [4Fe-4S] cluster, mechanism of activation of the enzyme by Fe2+, overview
additional information
IRP1 is a cytosolic isozyme devoid of labile Fe2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S(1,1,2,2)-tetrafluoroethyl-L-cysteine
inhibition of renal aconitase activity both in vivo and in vitro is a functional consequence of difluorothioamidyl-L-lysine formation by S(1,1,2,2)-tetrafluoroethyl-L-cysteine
citrate
citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation
H2O2
-
H2O2 does not exert its inhibitory effects by acting directly on the enzyme, rather inactivation appears to result from interactions between aconitase and a mitochondrial membrane component responsive to H2O2. Prolonged exposure of mitochondria to steady-state levels of H2O2 or O2- results in disassembly of the [4Fe-4S]2+ cluster, carbonylation, and protein degradation
indomethacin
-
a non-steroidal anti-inflammatory drug, carbonylation of aconitase and release of iron along with the loss of activity in vivo after indomethacin treatment, activation of mitochondrial death pathway by indomethacin, overview
Mn2+
-
inhibition of enzyme, resulting in up to 90% increase in intracellular citrate. Mitochondrial isoform is significantly more sensitive to Mn2+ than cytosolic isoform. Inhibition leads to conversion of enzyme to iron regulatory protein IRP 1 and increases the abundance of IRP2, leading to reduced H-ferritin expression, inreased transferrin receptor expression, and increased uptake of transferrin. IRP2 has a dominant role in Mn2+-induced alteration of iron homeostasis over aconitase/IRP1
peroxynitrite
-
i.e. ONOO-. 0.03-3 mM L-Cys, 0.03-3 mM glutathione, or 0.1-3 mM N-(2-mercaptopropionyl)glycine protects. 1 mM FeSO4 markedly enhances the protection provided by L-Cys, but not by glutathione or N-(2-mercaptopropionyl)glycine
Zn2+
-
competitive, the inhibitory effect is specific for the citrate to cis-aconitate reaction
additional information
-
enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues
-
additional information
enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lipoic acid
-
causes an increase in cardiac enzyme activity at doses of 35 and 70 mg/kg of 1.3 and 2.4fold in the animals
additional information
-
the maximal activity requires the presence of sulfhydryl compounds in the medium
-
additional information
the maximal activity requires the presence of sulfhydryl compounds in the medium
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
Fluorocitrate
Rattus norvegicus
-
pH 7.4, temperature not specified in the publication, tissue: brain
0.012
Fluorocitrate
Rattus norvegicus
-
pH 7.4, temperature not specified in the publication, tissue: heart
0.024
Fluorocitrate
Rattus norvegicus
-
pH 7.4, temperature not specified in the publication, tissue: kidney
0.024
Fluorocitrate
Rattus norvegicus
-
pH 7.4, temperature not specified in the publication, tissue: liver
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.011 - 0.06
-
aconitate hydratase in blood serum of control rats and rats subjected to myocardial ischemia and treatment with lipoic acid, overview
0.068 - 0.198
-
aconitate hydratase in myocardium of control rats and rats subjected to myocardial ischemia and treatment with lipoic acid, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
mitochondrial aconitase is over-expressed in primary mesencephalic cultures
-
activity is significantly higher in bone marrow of rats treated with N-nitro-L-arginine methylester
-
undifferentiated neonatal cardiomyocyte. In heat-shocked cells aconitase activity is reduced
-
activity is significantly higher in spleen of rats treated with N-nitro-L-arginine methylester
inactive isozyme mAH multimers occur in rat brain in a model of Huntingtons disease
-
aconitase-specific activity increases by 42% at 2% O2 compared to 21% O2
-
changes in enzyme activity in myocardial ischemia are coupled to accumulation of citrate, overview
-
aconitase-specific activity increases by 12% at 2% O2 compared to 21% O2
-
activity is significantly higher in liver of rats treated with N-nitro-L-arginine methylester
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
particulate-bound mitochondrial enzyme, the soluble mitochondrial enzyme is released from the mitochondria by freezing and thawing
-
24 h after intraperitoneal administration of endotoxin, there is a 28% reduction in mitochondrial respiration and a 24% reduction in aconitase activity. Functional activity of the electron transport chain is unaffected
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
it is investigated if oxidative inactivation of mitochondrial aconitase results in the release of redox-active iron and hydrogen peroxide and whether this contributes to cell death. Using an adenoviral construct mitochondrial aconitase is over-expressed in primary mesencephalic cultures. Oxidative inactivation of m-aconitase over-expressing cultures results in exacerbation of H2O2 production, Fe2+ accumulation and increased neuronal death. Increased cell death in m-aconitase overexpressing cultures is attenuated by addition of catalase and/or a cell permeable iron chelator suggesting that neuronal death occurred in part via astrocyte-derived H2O2
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ACON_RAT
780
0
85433
Swiss-Prot
Mitochondrion (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
peptide mapping, mass spectrometry analysis, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphorylation of mitochondrial aconitase by PKCbeta2 has regulatory function, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center
additional information
naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pickworth Glusker, J.
Aconitase
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
5
413-439
1971
Aspergillus niger, Bacillus subtilis, Bos taurus, Saccharomyces cerevisiae, Oryctolagus cuniculus, Glycine max, Rattus norvegicus, Rheum sp., Salmonella enterica subsp. enterica serovar Typhimurium, Sinapis alba, Solanum tuberosum, Sus scrofa
-
Guarriero-Bobyleva, V.; Volpi-Becchi, M.A.; Masini, A.
Parallel partial purification of cytoplasmic and mitochondrial aconitate hydratases from rat liver
Eur. J. Biochem.
34
455-458
1973
Rattus norvegicus
Zheng, W.; Ren, S.; Graziano, J.H.
Manganese inhibits mitochondrial aconitase: a mechanism of manganese neurotoxicity
Brain Res.
799
334-342
1998
Rattus norvegicus
Costello, L.C.; Liu, Y.; Franklin, R.B.; Kennedy, M.C.
Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells
J. Biol. Chem.
272
28875-28881
1997
Bos taurus, Rattus norvegicus, Sus scrofa
Cheung, P.Y.; Danial, H.; Jong, J.; Schulz, R.
Thiols protect the inhibition of myocardial aconitase by peroxynitrite
Arch. Biochem. Biophys.
350
104-108
1988
Rattus norvegicus
Ho, K.P.; Xiao, D.S.; Ke, Y.; Qian, Z.M.
Exercise decreases cytosolic aconitase activity in the liver, spleen, and bone marrow in rats
Biochem. Biophys. Res. Commun.
282
264-267
2001
Rattus norvegicus
James, E.A.; Gygi, S.P.; Adams, M.L.; Pierce, R.H.; Fausto, N.; Aebersold, R.H.; Nelson, S.D.; Bruschi, S.A.
Mitochondrial aconitase modification, functional inhibition, and evidence for a supramolecular complex of the TCA cycle by the renal toxicant S-(1,1,2,2-tetrafluoroethyl)-L-cysteine
Biochemistry
41
6789-6797
2002
Rattus norvegicus (Q9ER34), Rattus norvegicus Male Fischer 344 (Q9ER34)
Bulteau, A.L.; Ikeda-Saito, M.; Szweda, L.I.
Redox-dependent modulation of aconitase activity in intact mitochondria
Biochemistry
42
14846-14855
2003
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Ilangovan, G.; Venkatakrishnan, C.D.; Bratasz, A.; Osinbowale, S.; Cardounel, A.J.; Zweier, J.L.; Kuppusamy, P.
Heat shock-induced attenuation of hydroxyl radical generation and mitochondrial aconitase activity in cardiac H9c2 cells
Am. J. Physiol.
290
C313-324
2006
Rattus norvegicus
Sreedhar, B.; Nair, K.M.
Iron dependence and zinc inhibition of duodenal cytosolic aconitase of rat
Indian J. Biochem. Biophys.
41
250-253
2004
Rattus norvegicus
Mason, K.E.; Stofan, D.A.
Endotoxin challenge reduces aconitase activity in myocardial tissue
Arch. Biochem. Biophys.
469
151-156
2008
Rattus norvegicus
Crooks, D.R.; Ghosh, M.C.; Braun-Sommargren, M.; Rouault, T.A.; Smith, D.R.
Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells
J. Neurosci. Res.
85
1797-1809
2007
Rattus norvegicus
Makeeva, A.V.; Popova, T.N.; Matasova, L.V.; Yama, I.N.
Effects of lipoic acid on citrate content, aconitate hydratase activity, and oxidative status during myocardial ischemia in rats
Biochemistry (Moscow)
73
76-79
2008
Rattus norvegicus
Matasova, L.V.; Popova, T.N.
Aconitate hydratase of mammals under oxidative stress
Biochemistry (Moscow)
73
957-964
2008
Homo sapiens, Homo sapiens (P21399), Mus musculus, Mus musculus (P28271), Rattus norvegicus, Rattus norvegicus (Q63270)
Lin, G.; Brownsey, R.W.; Macleod, K.M.
Regulation of mitochondrial aconitase by phosphorylation in diabetic rat heart
Cell. Mol. Life Sci.
66
919-932
2009
Rattus norvegicus (Q9ER34)
Maity, P.; Bindu, S.; Dey, S.; Goyal, M.; Alam, A.; Pal, C.; Mitra, K.; Bandyopadhyay, U.
Indomethacin, a non-steroidal anti-inflammatory drug, develops gastropathy by inducing reactive oxygen species-mediated mitochondrial pathology and associated apoptosis in gastric mucosa: a novel role of mitochondrial aconitase oxidation
J. Biol. Chem.
284
3058-3068
2009
Rattus norvegicus
Cantu, D.; Schaack, J.; Patel, M.
Oxidative inactivation of mitochondrial aconitase results in iron and H2O2-mediated neurotoxicity in rat primary mesencephalic cultures
PLoS ONE
4
e7095
2009
Rattus norvegicus (Q9ER34)
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