Itaconic Acid is a Mammalian Metabolite Induced During Macrophage Activation

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2011 Sep 17

PMID 21919507

Citations 181

Authors

Cheryl L Strelko

Wenyun Lu

Fay J Dufort

Thomas N Seyfried

Thomas C Chiles

Joshua D Rabinowitz

Mary F Roberts

Affiliations

Soon will be listed here.

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-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.

Citing Articles

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