Document Detail

Itaconic acid is a mammalian metabolite induced during macrophage activation.
MedLine Citation:
PMID:  21919507     Owner:  NLM     Status:  MEDLINE    
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.
Cheryl L Strelko; Wenyun Lu; Fay J Dufort; Thomas N Seyfried; Thomas C Chiles; Joshua D Rabinowitz; Mary F Roberts
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-09-27
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  133     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-12     Completed Date:  2012-02-03     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16386-9     Citation Subset:  IM    
Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, USA.
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MeSH Terms
Cell Line, Tumor
Interferon-gamma / pharmacology
Lipopolysaccharides / pharmacology
Macrophages / drug effects,  metabolism*
Succinates / analysis,  metabolism*
Grant Support
1RC1 CA147961/CA/NCI NIH HHS; RC1 CA147961-02/CA/NCI NIH HHS
Reg. No./Substance:
0/Lipopolysaccharides; 0/Succinates; 82115-62-6/Interferon-gamma; 97-65-4/itaconic acid

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