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Literature summary extracted from

  • Matasova, L.V.; Popova, T.N.
    Aconitate hydratase of mammals under oxidative stress (2008), Biochemistry (Moscow), 73, 957-964.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
4.2.1.3 additional information the maximal activity requires the presence of sulfhydryl compounds in the medium Mus musculus
4.2.1.3 additional information the maximal activity requires the presence of sulfhydryl compounds in the medium Rattus norvegicus

Protein Variants

EC Number Protein Variants Comment Organism
4.2.1.3 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 Rattus norvegicus
4.2.1.3 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 Mus musculus
4.2.1.3 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 Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
4.2.1.3 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 Homo sapiens
4.2.1.3 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 Mus musculus
4.2.1.3 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 Rattus norvegicus
4.2.1.3 fructose-6-phosphate
-
 Homo sapiens
4.2.1.3 fructose-6-phosphate
-
 Mus musculus
4.2.1.3 fructose-6-phosphate
-
 Rattus norvegicus
4.2.1.3 additional information superoxide inactivates the mRNA-binding activity through direct chemical attack, enzyme competitive inhibition by di- and tricarboxylic acids and inactivation due to modification of cysteine and tyrosine residues, e.g. S-glutathionylation Homo sapiens
4.2.1.3 additional information superexpression of mitochondrial ferritin in mouse cells leads to iron deficiency in the cytosol, decrease in the level of cytosolic ferritin, and inhibition of cAH and mAH isozyme activities. Enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues Mus musculus
4.2.1.3 additional information enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues; enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues Rattus norvegicus
4.2.1.3 Oxalomalate inhibition of the enzyme by oxalomalate reduces glutamate secretion and eliminates the effect of iron ions on the latter Homo sapiens
4.2.1.3 oxalosuccinate
-
 Homo sapiens
4.2.1.3 oxalosuccinate
-
 Mus musculus
4.2.1.3 oxalosuccinate
-
 Rattus norvegicus
4.2.1.3 peroxynitrite inactivation due to the release of iron from the Fe-S cluster, other nitric oxide sources decrease the activity of the mitochondrial isozyme Homo sapiens
4.2.1.3 superoxide anion radical
-
 Mus musculus
4.2.1.3 superoxide anion radical
-
 Rattus norvegicus
4.2.1.3 trans-aconitate a competitive inhibitor of the enzyme with respect to cis-aconitate and a non-competitive inhibitor with respect to citrate and isocitrate Homo sapiens
4.2.1.3 Zn2+ a specific inhibitor of mitochondrial isozyme Mus musculus
4.2.1.3 Zn2+ a specific inhibitor of mitochondrial isozyme Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
4.2.1.3 cytosol cytosolic isozyme cAH Mus musculus 5829
-
4.2.1.3 cytosol cytosolic isozyme cAH Rattus norvegicus 5829
-
4.2.1.3 cytosol cytosolic isozyme cAH, IRP1 is a cytosolic isozyme devoid of labile Fe2+ Homo sapiens 5829
-
4.2.1.3 cytosol IRP1 is a cytosolic isozyme devoid of labile Fe2+ Rattus norvegicus 5829
-
4.2.1.3 cytosol IRP1 is a cytosolic isozyme devoid of labile Fe2+ Mus musculus 5829
-
4.2.1.3 mitochondrion mitochondrial isozyme mAH Mus musculus 5739
-
4.2.1.3 mitochondrion mitochondrial isozyme mAH Rattus norvegicus 5739
-
4.2.1.3 mitochondrion mitochondrial isozyme mAH Homo sapiens 5739
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
4.2.1.3 Fe2+ required Homo sapiens
4.2.1.3 Fe2+ required, binding structure in the [4Fe-4S] cluster, mechanism of activation of the enzyme by Fe2+, overview Rattus norvegicus
4.2.1.3 Fe2+ required, binding structure in the [Fe-S] cluster, mechanism of activation of the enzyme by Fe2+, overview Mus musculus
4.2.1.3 Fe2+ required, both isoenzymes have an [4Fe-4S] iron-sulfur cluster bound with cysteine residues Cys437, Cys503, and Cys506, under the action of reductants, the active enzyme form is produced with a complex cation of the [3Fe–3S]2+ type, structure, and mechanism of activation of the enzyme by Fe2+, overview Homo sapiens
4.2.1.3 additional information IRP1 is a cytosolic isozyme devoid of labile Fe2+ Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.2.1.3 additional information Rattus norvegicus 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 ?
-
 ?
4.2.1.3 additional information Rattus norvegicus 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 ?
-
 ?
4.2.1.3 additional information Mus musculus role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview ?
-
 ?
4.2.1.3 additional information Homo sapiens role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Blocking of isozyme mAH expression and activity by 40-60% causes a decrease in ATP biosynthesis, increase in citrate secretion, and reduction of the rate of proliferation of human prostate carcinoma cells. extracellular H2O2 strongly induces IRP1 through a signal cascade, introduction of a source of iron ions enhances glutamate secretion in cultivated lens cells and neurons through an increase in cAH activity and intensification of isocitrate formation. The maximal activity requires the presence of sulfhydryl compounds in the medium ?
-
 ?
4.2.1.3 additional information Homo sapiens role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. A decrease in enzyme activity is observed in some neurodegenerative diseases associated with the development of oxidative stress, in particular, Parkinson’s and Alzheimer’s diseases. Regulation, overview. Extracellular H2O2 strongly induces IRP1 through a signal cascade ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
4.2.1.3 Homo sapiens
-
-
-
4.2.1.3 Homo sapiens P21399 IRP1
-
4.2.1.3 Mus musculus
-
-
-
4.2.1.3 Mus musculus P28271
-
-
4.2.1.3 Rattus norvegicus
-
-
-
4.2.1.3 Rattus norvegicus Q63270 IRP1
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
4.2.1.3 phosphoprotein mechanism controlling IRP1 activity at the level of its stability can be phosphorylation of Ser138, Ser138, Ser711, and flanking sequences are highly conserved Homo sapiens

Purification (Commentary)

EC Number Purification (Comment) Organism
4.2.1.3 native IRP1 from liver Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
4.2.1.3 A-549 cell
-
 Homo sapiens
-
4.2.1.3 brain inactive isozyme mAH multimers occur in rat brain in a model of Huntington’s disease Rattus norvegicus
-
4.2.1.3 heart
-
 Homo sapiens
-
4.2.1.3 HEK-293 cell
-
 Homo sapiens
-
4.2.1.3 hepatoma cell
-
 Mus musculus
-
4.2.1.3 kidney
-
 Homo sapiens
-
4.2.1.3 liver
-
 Mus musculus
-
4.2.1.3 liver
-
 Homo sapiens
-
4.2.1.3 liver
-
 Rattus norvegicus
-
4.2.1.3 additional information isozymes cAH and mAH are present in all tissues, and are most active in the heart, kidney, and liver Homo sapiens
-
4.2.1.3 PC-12 cell
-
 Rattus norvegicus
-
4.2.1.3 prostate gland mitochondrial isozyme plays the key role in the bioenergetic theory of malignant transformation of the prostate Homo sapiens
-
4.2.1.3 prostate gland cancer cell line
-
 Homo sapiens
-
4.2.1.3 umbilical vein endothelial cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.2.1.3 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 Rattus norvegicus ?
-
 ?
4.2.1.3 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 Rattus norvegicus ?
-
 ?
4.2.1.3 additional information role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview Mus musculus ?
-
 ?
4.2.1.3 additional information role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Blocking of isozyme mAH expression and activity by 40-60% causes a decrease in ATP biosynthesis, increase in citrate secretion, and reduction of the rate of proliferation of human prostate carcinoma cells. extracellular H2O2 strongly induces IRP1 through a signal cascade, introduction of a source of iron ions enhances glutamate secretion in cultivated lens cells and neurons through an increase in cAH activity and intensification of isocitrate formation. The maximal activity requires the presence of sulfhydryl compounds in the medium Homo sapiens ?
-
 ?
4.2.1.3 additional information role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. A decrease in enzyme activity is observed in some neurodegenerative diseases associated with the development of oxidative stress, in particular, Parkinson’s and Alzheimer’s diseases. Regulation, overview. Extracellular H2O2 strongly induces IRP1 through a signal cascade Homo sapiens ?
-
 ?
4.2.1.3 additional information IRP shows RNA-binding activity, which is affected by some hormones and growth factors, e.g. thyroid, erythropoietin, and epidermal growth factor Rattus norvegicus ?
-
 ?

Subunits

EC Number Subunits Comment Organism
4.2.1.3 ? x * 95000-100000, IRP1, SDS-PAGE Rattus norvegicus
4.2.1.3 More depending on the conditions, the enzyme can associate to dimer, trimer, and tetramer forms, followed by the loss of enzyme activity Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
4.2.1.3 aconitase
-
 Mus musculus
4.2.1.3 aconitase
-
 Homo sapiens
4.2.1.3 aconitase
-
 Rattus norvegicus
4.2.1.3 Aconitate hydratase
-
 Mus musculus
4.2.1.3 Aconitate hydratase
-
 Homo sapiens
4.2.1.3 Aconitate hydratase
-
 Rattus norvegicus
4.2.1.3 IRP1
-
 Rattus norvegicus
4.2.1.3 IRP1
-
 Mus musculus
4.2.1.3 IRP1
-
 Homo sapiens