Reaction participants Show >> << Hide
- Name help_outline cis-aconitate Identifier CHEBI:16383 Charge -3 Formula C6H3O6 InChIKeyhelp_outline GTZCVFVGUGFEME-IWQZZHSRSA-K SMILEShelp_outline [O-]C(=O)C\C(=C\C([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 5 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CO2 Identifier CHEBI:16526 (Beilstein: 1900390; CAS: 124-38-9) help_outline Charge 0 Formula CO2 InChIKeyhelp_outline CURLTUGMZLYLDI-UHFFFAOYSA-N SMILEShelp_outline O=C=O 2D coordinates Mol file for the small molecule Search links Involved in 980 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline itaconate Identifier CHEBI:17240 (Beilstein: 3904702; CAS: 2964-00-3) help_outline Charge -2 Formula C5H4O4 InChIKeyhelp_outline LVHBHZANLOWSRM-UHFFFAOYSA-L SMILEShelp_outline C(C(CC([O-])=O)=C)([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:15253 | RHEA:15254 | RHEA:15255 | RHEA:15256 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Cloning and functional characterization of the cis-aconitic acid decarboxylase (CAD) gene from Aspergillus terreus.
Kanamasa S., Dwiarti L., Okabe M., Park E.Y.
A filamentous fungus Aspergillus terreus produces itaconic acid, which is predicted to be derived from cis-aconitic acid via catalysis by cis-aconitic acid decarboxylase (CAD) in the carbon metabolism of the fungus. To clarify the enzyme's function and a pathway for itaconic acid biosynthesis, we ... >> More
A filamentous fungus Aspergillus terreus produces itaconic acid, which is predicted to be derived from cis-aconitic acid via catalysis by cis-aconitic acid decarboxylase (CAD) in the carbon metabolism of the fungus. To clarify the enzyme's function and a pathway for itaconic acid biosynthesis, we cloned a novel gene encoding the enzyme. The open reading frame of this gene (CAD1) consists of 1,529 bp encoding 490 amino acids and is interrupted by a single intron. Among the identified proteins in the database, the primary structure of the protein encoded by CAD1 shared high identity with the MmgE/PrpD family of proteins, including a number of 2-methylcitrate dehydratases of bacteria. The cloned gene excluding an intron was introduced into the expression plasmid pAUR-CAD1 controlled by the ADH1 promoter. The CAD activity in Saccharomyces cerevisiae was confirmed by directly detecting itaconic acid as a product from cis-aconitic acid as a substrate. This result reveals for the first time that this gene encodes CAD, which is essential for itaconic acid production in A. terreus. << Less
Appl. Microbiol. Biotechnol. 80:223-229(2008) [PubMed] [EuropePMC]
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Biosynthesis of itaconic acid in Aspergillus terreus. III. The properties and reaction mechanism of cis-aconitic acid decarboxylase.
BENTLEY R., THIESSEN C.P.
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Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production.
Michelucci A., Cordes T., Ghelfi J., Pailot A., Reiling N., Goldmann O., Binz T., Wegner A., Tallam A., Rausell A., Buttini M., Linster C.L., Medina E., Balling R., Hiller K.
Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylati ... >> More
Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis-aconitate, a tricarboxylic acid cycle intermediate. Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found Irg1 expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect. We purified IRG1 protein and identified its cis-aconitate decarboxylating activity in an enzymatic assay. Itaconic acid is an organic compound that inhibits isocitrate lyase, the key enzyme of the glyoxylate shunt, a pathway essential for bacterial growth under specific conditions. Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as Salmonella enterica and Mycobacterium tuberculosis. Furthermore, Irg1 gene silencing in macrophages resulted in significantly decreased intracellular itaconic acid levels as well as significantly reduced antimicrobial activity during bacterial infections. Taken together, our results demonstrate that IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production. << Less
Proc. Natl. Acad. Sci. U.S.A. 110:7820-7825(2013) [PubMed] [EuropePMC]