Effect of IDH1 mutations on the cellular metabolome

A chemical similarity network visualization of how  point mutations R132 and R172 in IDH1 and IDH2 are affecting the cellular metabolome in cultured cells ?. 

 

Red means : higher in mutants 

Blue means : higher in wild type

no label : significant (p<0.05) but fold was less than 0.50 (+/-)

Node size reflect ; fold change

highest fold change was 160 ; 2HG

http://www.pnas.org/content/early/2011/02/01/1019393108.abstract 

Abstract:- 

Point mutations of the NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream effects of mutant IDH1 and IDH2 proteins or of 2HG on cellular metabolism are unknown. We profiled >200 metabolites in human oligodendroglioma (HOG) cells to determine the effects of expression of IDH1 and IDH2 mutants. Levels of amino acids, glutathione metabolites, choline derivatives, and tricarboxylic acid (TCA) cycle intermediates were altered in mutant IDH1- and IDH2-expressing cells. These changes were similar to those identified after treatment of the cells with 2HG. Remarkably, N-acetyl-aspartyl-glutamate (NAAG), a common dipeptide in brain, was 50-fold reduced in cells expressing IDH1 mutants and 8.3-fold reduced in cells expressing IDH2 mutants. NAAG also was significantly lower in human glioma tissues containing IDH mutations than in gliomas without such mutations. These metabolic changes provide clues to the pathogenesis of tumors associated with IDH gene mutations.

Around 55 metabolites were could not be mapped into the network graphs because they could not be associated with any PubChem cid which is essential for generating the similarity matrix underlying these network graphs.