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Itaconic acid is a mammalian metabolite induced during macrophage activation.

ABSTRACT: Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and (13)C-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-? 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.

SUBMITTER: Strelko CL

PROVIDER: S-EPMC3216473 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Itaconic acid is a mammalian metabolite induced during macrophage activation.

Strelko Cheryl L CL Lu Wenyun W Dufort Fay J FJ Seyfried Thomas N TN Chiles Thomas C TC Rabinowitz Joshua D JD Roberts Mary F MF

Journal of the American Chemical Society 20110927 41

Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and (13)C-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 ...[more]

PMID: 21919507

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