Itaconic acid is a mammalian metabolite induced during macrophage activation

Cheryl L. Strelko, Wenyun Lu, Fay J. Dufort, Thomas N. Seyfried, Thomas C. Chiles, Joshua D. Rabinowitz, Mary F. Roberts

Research output: Contribution to journalArticlepeer-review

254 Scopus citations


Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and 13C-labeling, we have detected ITA in both macrophage-like VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased ITA production and secretion. Crude cell extracts synthesize ITA via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.

Original languageEnglish (US)
Pages (from-to)16386-16389
Number of pages4
JournalJournal of the American Chemical Society
Issue number41
StatePublished - Oct 19 2011

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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