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. 2020 Oct 21;8:23. doi: 10.1186/s40170-020-00229-2

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — a Simplified representation of the TCA cycle and its link with IDH1 enzyme and glutamine. b ¹H NMR representative spectrum of an IDH1^mut glioma cell line after 10 μM AGI5198 treatment for 72 h (black) or DMSO (gray). The 2HG chemical structure is displayed (upper left insert) with carbon atom numbering included. Boxed areas denote regions for the two protons linked to C4 and one to the C3 (Hb) group, since the remaining one (Ha) is overlaid by the larger proline resonance centered at 1.98 ppm. c 2HG, d glutamine, and e glutamate intensities normalized to protein content from polar extracts of IDH1^mut cell lines after 10, 25, and 50 μM AGI5198 treatment for 72 h or DMSO obtained by LCMS analysis. Bar plots depicting the normalized intensities from n = 3 samples per experiment. *p < 0.05; **p < 0.005; ***p < 0.001 from a one-way ANOVA followed by Tukey’s HSD test for multiple comparisons. f Contribution of glucose and glutamine to 2HG formation obtained by LCMS analysis from 2 independent experiments involving the aforementioned ¹³C probes. Bar plots displaying mean ± SD from adjusted percentages (n = 3)