Itaconic Acid Is a Mammalian Metabolite Induced during Macrophage Activation

作者：Strelko Cheryl L; Lu Wenyun; Dufort Fay J; Seyfried Thomas N; Chiles Thomas C; Rabinowitz Joshua D; Roberts Mary F^*

来源：Journal of the American Chemical Society, 2011, 133(41): 16386-16389.

DOI：10.1021/ja2070889

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-gamma 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 bio-synthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.

• 出版日期2011-10-19