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Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome
Open accessAbstract
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.
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“a portion of the succinate that accumulates during ischemia and inflammation is released from the cell into the extracellular environment through poorly defined processes. This occurs following IR injury158,159, inflammation10, or cold exposure160.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [159]
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Items 201–300 of 451
Lazović, J., Soto, H., Piccioni, D. E., Ru, J. R. L., Li, S., Mirsadraei, L., Yong, W. H., Prins, R. M., Liau, L. M., Ellingson, B. M., et al. (2012) · Neuro-Oncology · doi:10.1093/neuonc/nos258 · Cited by 42
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BackgroundMutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression
Pirozzi, C. J., Carpenter, A. B., Waitkus, M. S., Wang, C. Y., Zhu, H., Hansen, L. J., Chen, L. H., Greer, P. K., Feng, J., Wang, Y., et al. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0485 · Cited by 42
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“(40), it is possible that decreased nuclear PKM2 levels in IDH1-R132H cells also contribute to the altered metabolic profile observed for these tumors (41).”
BackgroundProteomics and metabolomics approach in adult and pediatric glioma diagnostics
Pienkowski, T., Kowalczyk, T., Garcia‐Romero, N., Ayuso‐Sacido, Á., & Ciborowski, M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188721 · Cited by 41
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“This depletion of Glu(18,32) might additionally result in elevated conversion of Gln to Glu by glutaminase resulting also in decreased Gln levels in IDH-mutant tumors.(18) Overall, our findings are consistent with an elevated flux from Gln via Glu to a-KG due to IDH-induced conversion of a-KG.”
BackgroundResultMutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity
Chittaranjan, S., Chan, S. Y., Yang, C. P., Yang, K., Chen, V., Moradian, A., Firme, M. R., Song, J., Go, N. E., Blough, M. D., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2401 · Cited by 44
“com/oncotarget was previously determined not to harbour 1p19q codeletions or mutations in the IDH1 or IDH2 genes [35, 36].”
BackgroundJuratli, T. A., Peitzsch, M., Geiger, K. D., Schackert, G., Eisenhofer, G., & Krex, D. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not006 · Cited by 40
Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells
Smolková, K., Dvořák, A., Zelenka, J., Vı́tek, L., & Ježek, P. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.05.012 · Cited by 39
“Heterozygous IDH mutations have been found typically in grade 2 and 3 gliomas (Chou et al., 2012; Ichimura, 2012; Jenkins et al., 2012), secondary glioblastomas (Krell et al., 2011; Reitman et al., 2011; Ward et al., 2011), or acute myeloid leukemia (Patel et al., 2011; Shih et al., 2012).”
BackgroundVolumetric spiral chemical shift imaging of hyperpolarized [2‐13c]pyruvate in a rat c6 glioma model
Park, J. M., Josan, S., Jang, T., Merchant, M. J., Watkins, R., Hurd, R. E., Recht, L. D., Mayer, D., & Spielman, D. M. (2015) · Magnetic Resonance in Medicine · doi:10.1002/mrm.25766 · Cited by 39
“For example, glutamate production can be affected by upregulated isocitrate dehydrogenase (IDH) (32,33) activity or Myc-associated increase of glutamine uptake and glutaminase activity in several types of glioma (34,35).”
BackgroundMetabolomic effects in HepG2 cells exposed to four TiO 2 and two CeO 2 nanomaterials
Kitchin, K. T., Grulke, E. A., Robinette, B. L., & Castellon, B. T. (2014) · Environmental Science Nano · doi:10.1039/c4en00096j · Cited by 39
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“The IDHs include IDH1 in the cytoplasm and IDH2 in the mitochondria, which catalyze an identical reaction [17] (Additional file 1: Figure S1).”
BackgroundMagnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics
Varoquaux, A. D., Fur, Y. L., Impériale, A., Reyre, A., Montava, M., Fakhry, N., Namer, I. J., Moulin, G., Pacák, K., Guye, M., et al. (2015) · Endocrine Related Cancer · doi:10.1530/erc-15-0246 · Cited by 39
“Maturing right behind genomics, transcriptomics, and proteomics, metabolomics is the comprehensive analysis of small molecule metabolites (Reitman et al. 2011).”
Zhu, H., Zhang, Y., Chen, J., Qiu, J., Huang, K., Wu, M., & Xia, C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169038 · Cited by 39
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“(Durham, NC) for metabolomic profiling analysis as described previously (54).”
Beyond the Influence of IDH Mutations: Exploring Epigenetic Vulnerabilities in Chondrosarcoma
Venneker, S., Kruisselbrink, A. B., Baranski, Z., Palubeckaitė, I., Bruijn, I. H. B., Oosting, J., French, P. J., Danen, E. H. J., & Bovée, J. V. M. G. (2020) · Cancers · doi:10.3390/cancers12123589 · Cited by 39
“Due to the high structural similarity between α-KG and its antagonist D-2-HG, α-KG dependent enzymes are inhibited by the high levels of the oncometabolite [10,11], causing widespread changes in the metabolic state, DNA damage repair mechanisms, and growth signaling pathways [12,13].”
BackgroundMolecular Imaging of Metabolic Reprograming in Mutant IDH Cells
Viswanath, P., Chaumeil, M. M., & Ronen, S. M. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00060 · Cited by 38
“From a metabolic perspective, mutations in IDH1 and IDH2 lead not only to the loss of wild-type enzyme activity [interconversion of isocitrate to α-ketoglutarate (α-KG)] but also to a gain-of-function that results in the conversion of α-KG to the “oncometabolite” 2-hydroxyglutarate (2-HG) (43).”
MethodInfluentialOizel, K., Gratas, C., Nadaradjane, A., Oliver, L., Vallette, F. M., & Pecqueur, C. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.13 · Cited by 38
“Indeed, besides being an inhibitor of LDH, oxamate also inhibits AAT.33,34 In our study, oxamate did not decrease lactate secretion as predicted by its LDH inhibitory action but instead prevented the mitochondrial respiratory reserve loss only in mutant IDH-overexpressing cells.”
BackgroundClinical aggressiveness of malignant gliomas is linked to augmented metabolism of amino acids
Panosyan, E. H., Lasky, J. L., Lin, H. J., Lai, A., Yang, H. Y., Guo, X., Quinn, M. A., Nelson, S. F., Cloughesy, T. F., & Nghiemphu, P. L. (2016) · Journal of Neuro-Oncology · doi:10.1007/s11060-016-2073-5 · Cited by 36
“Because isocitrate dehydrogenase (IDH) status varies in molecular subclasses of gliomas and glioblastomas [13], it may also be reasonable to expect IDH status to be associated with different patterns of amino acid metabolism [7, 14].”
BackgroundFrom Laboratory Studies to Clinical Trials: Temozolomide Use in IDH-Mutant Gliomas
Sun, X., & Turcan, Ş. (2021) · Cells · doi:10.3390/cells10051225 · Cited by 38
“IDH is a central enzyme of the TCA cycle; therefore, many studies have sought to understand the unique metabolic profiles reprogrammed by mutant IDH1 to therapeutically exploit these metabolic vulnerabilities [16] (Figure 2).”
BackgroundMostafavi, S., Zalpoor, H., & Hassan, Z. M. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-022-00356-2 · Cited by 41
“Its function as an oncometabolites was established by involving the inhibition of alpha-ketoglutarate-dependent dioxygenases [135].”
BackgroundMutant IDH1 expression is associated with down-regulation of monocarboxylate transporters
Viswanath, P., Najac, C., Izquierdo-García, J. L., Pankov, A., Hong, C., Eriksson, P., Costello, J., Pieper, R. O., & Ronen, S. M. (2016) · Oncotarget · doi:10.18632/oncotarget.9006 · Cited by 35
“also found reduced levels of phosphocholine (PC) and increased levels of glycerophosphocholine (GPC) in mutant IDH1 glioma cells relative to wild-type cells [22] and these results were in line with a subsequent study by Esmaeili et al.”
Kim, H., Kim, S., Lee, H. H., & Heo, H. (2016) · Korean Journal of Radiology · doi:10.3348/kjr.2016.17.5.620 · Cited by 36
Venneker, S., Kruisselbrink, A. B., Bruijn, I. H. B., de Jong, Y., van Wijnen, A. J., Danen, E. H. J., & Bovée, J. V. M. G. (2019) · Cancers · doi:10.3390/cancers11121918 · Cited by 36
“Furthermore, mutations in IDH1 or IDH2 (collectively referred to as IDH) cause alterations in cell metabolism, cell growth signalling pathways, and the DNA damage response [9,10].”
BackgroundOptical Analysis of Glioma: Fourier-Transform Infrared Spectroscopy Reveals the IDH1 Mutation Status
Uckermann, O., Juratli, T. A., Galli, R., Conde, M., Wiedemuth, R., Krex, D., Geiger, K. D., Temme, A., Schackert, G., Koch, E., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1795 · Cited by 36
“This is consistent with variations of amino acid levels in IDH1-mutated cell lines and tumor tissue that have been reported by others: IDH1-mutated cell lines showed elevated levels of glycine, serine, threonine, asparagine, phenylalanine, tyrosine, tryptophan, and methionine, whereas aspartate was decreased (40).”
BackgroundResult2-Hydroxyglutarate as a Magnetic Resonance Biomarker for Glioma Subtyping
Esmaeili, M., Vettukattil, R., & Bathen, T. F. (2013) · Translational Oncology · doi:10.1593/tlo.12424 · Cited by 35
“Kalinina et al. [28] investigated whether the presence of 2-HG in glioma cohorts was reflected as a consequence of IDH1/IDH2 mutations across the subtypes and grades including nontumorous controls.”
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Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer
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“Moreover, growth factor-mediated phosphorylation of pyruvate kinase isoform 2 (PKM2) [14] and mutations of genes in IDH1/2 [15] in the metabolic pathways such as glycolysis and the TCA cycle respectively have been identified that support growth of the rapidly proliferating cells and survive metabolic stress [16,17].”
Self-citationJiménez‐Morales, S., Pérez-Amado, C. J., Langley, E., & Hidalgo‐Miranda, A. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4468 · Cited by 34
“Notably, it has been observed that tumors carrying IDH mutations have few or no somatic mtDNA mutations (79).”
Zorofchian, S., Iqbal, F., Rao, M., Aung, P. P., Esquenazi, Y., & Ballester, L. Y. (2018) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2018-205414 · Cited by 33
“91 IDH1 (isocitrate dehydrogenase 1) is an enzyme located in the cytosol and peroxisome and converts isocitrate to α -keto- glutarate.”
Miyata, S., Tominaga, K., Sakashita, E., Urabe, M., Onuki, Y., Gomi, A., Yamaguchi, T., Mieno, M., Mizukami, H., Kume, A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-46217-5 · Cited by 33
Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin
Biedermann, J., Preussler, M., Conde, M., Peitzsch, M., Richter, S., Wiedemuth, R., Abou‐El‐Ardat, K., Krüger, A., Meinhardt, M., Schackert, G., et al. (2019) · Cancers · doi:10.3390/cancers11122028 · Cited by 36
“While there is one in vivo study reporting no change in TCA cycle metabolites in tissues from IDH1‐mutant gliomas compared to wildtype tumors [28], our results are in line with other in vitro data [29] and a recently published in vivo study showing that TCA metabolites were reduced in IDH1‐mutant patient‐derived xenog…”
ResultEffects of cellular senescence on metabolic pathways in non-immune and immune cells
Frasca, D., Saada, Y. B., Garcia, D., & Friguet, B. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111428 · Cited by 35
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NADP+-dependent IDH1R132 mutation and its relevance for glioma patient survival
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Radiomics, Metabolic, and Molecular MRI for Brain Tumors
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MR-detectable metabolic biomarkers of response to mutant IDH inhibition in low-grade glioma
Molloy, A. R., Najac, C., Viswanath, P., Lakhani, A., Subramani, E., Batsios, G., Radoul, M., Gillespie, A. M., Pieper, R. O., & Ronen, S. M. (2020) · Theranostics · doi:10.7150/thno.47317 · Cited by 32
“Beyond 2-HG detection, investigations of glioma cell models, tumor samples ex vivo, and patients in vivo have all demonstrated broad reprogramming of cellular metabolism that is associated with the IDH mutation [35-47].”
BackgroundResultCrispo, F., Pietrafesa, M., Condelli, V., Maddalena, F., Bruno, G., Piscazzi, A., Sgambato, A., Esposito, F., & Landriscina, M. (2020) · Molecules · doi:10.3390/molecules25163754 · Cited by 32
“, some amino acids, glutathione metabolites, choline derivatives, and TCA cycle intermediates) for which the 2-HG production by IDH1R132H neomorphic activity was not the unique factor responsible [105], but α-KG and NADPH availability became crucial in the rewiring of the metabolic landscape of cells carrying the muta…”
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“While amino acid metabolism has been investigated in either Hs683 or HOG cells [31,34], the effects of Gln deprivation have never been studied in these cells models.”
BackgroundPavlova, O., Fraitag, S., & Hohl, D. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.07.015 · Cited by 30
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Sirtuin activation targets IDH-mutant tumors
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“as previously described [25,26].”
Self-citationNicholas, D., Tang, H., Zhang, Q., Rudra, J. S., Xu, F., Langridge, W. H. R., & Zhang, K. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.035089 · Cited by 27
“Bioinformatic Analysis—Multivariate statistics analysis using the “R” program has previously been utilized for metabolic profiling (12).”
MethodIsocitrate dehydrogenase gene variants in cancer and their clinical significance
Cadoux-Hudson, T. A. D., Schofield, C. J., & McCullagh, J. (2021) · Biochemical Society Transactions · doi:10.1042/bst20210277 · Cited by 28
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A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy
Shen, X., Voets, N., Larkin, S. J., de Pennington, N., Stacey, R. J., Plaha, P., McCullagh, J., Schofield, C. J., Clare, S., Jezzard, P., et al. (2019) · Metabolites · doi:10.3390/metabo9020035 · Cited by 26
“This observation is consistent with an in vitro study showing a 20% increase in myo-Inositol level in IDH2 compared to IDH1 [26].”
ResultPotential role of Marine Bioactive Compounds in cancer signaling pathways: A review
Manoharan, S., & Perumal, E. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175330 · Cited by 27
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Keßler, J., Hohmann, T., Güttler, A., Petrenko, M., Ostheimer, C., Hohmann, U., Bache, M., Dehghani, F., & Vordermark, D. (2019) · Cancers · doi:10.3390/cancers11060889 · Cited by 28
“Under physiological conditions, IDH enzymes regulate a number of cellular functions and play an essential role in cellular protection as well as response to energetic and oxidative stress [29,31,36,70,71].”
BackgroundHamon, M., Ahmed, E. K., Baraibar, M. A., & Friguet, B. (2019) · PROTEOMICS · doi:10.1002/pmic.201800421 · Cited by 26
The Association between Whole‐Brain MR Spectroscopy and IDH Mutation Status in Gliomas
Goryawala, M., Lavi, E. S., Nagornaya, N., Heros, D. O., Komotar, R. J., & Maudsley, A. A. (2019) · Journal of Neuroimaging · doi:10.1111/jon.12685 · Cited by 25
Tan, J., Wang, H.-L., Yang, J., Liu, Q., Li, C., Wang, Y.-Q., Fu, L., Gao, Q., Chen, Y., & Fang, J. (2020) · Theranostics · doi:10.7150/thno.38087 · Cited by 25
“The metabolomic analysis was performed by Metabolon (Durham, NC, USA) using their previously described methods [13].”
MethodSelf-citationGlutathione biosynthesis is upregulated at the initiation of MYCN‐driven neuroblastoma tumorigenesis
Carter, D. R., Sutton, S. K., Pajic, M., Murray, J. E., Sekyere, E. O., Fletcher, J. I., Beckers, A., Preter, K. D., Speleman, F., George, R. E., et al. (2016) · Molecular Oncology · doi:10.1016/j.molonc.2016.02.004 · Cited by 25
Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes
Pathmanapan, S., Ilkayeva, O., Martin, J. T., Loe, A. K. H., Zhang, H., Zhang, G., Newgard, C. B., Wunder, J. S., & Alman, B. A. (2021) · Cancer & Metabolism · doi:10.1186/s40170-021-00247-8 · Cited by 25
“While findings in gliomas show depletion of the late-stage TCA cycle intermediates, fumarate and malate [49], we did not observe this in chondrosarcoma.”
BackgroundResultInfluentialFennessey, C. M., Ivie, S. E., & McClain, M. S. (2012) · Molecular BioSystems · doi:10.1039/c2mb25142f · Cited by 25
Long, P. M., Tighe, S. W., Driscoll, H. E., Moffett, J. R., Namboodiri, A. M. A., Viapiano, M. S., Lawler, S. E., & Jaworski, D. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080714 · Cited by 25
“Therefore, it would be intriguing to assess whether ASPA protein levels, ASPA subcellular localization, or GTA-mediated growth arrest are altered in cells bearing IDH1/2 mutations.”
BackgroundInfluentialGarrett-Bakelman, F. E., & Melnick, A. M. (2016) · Epigenomics · doi:10.2217/epi-2016-0008 · Cited by 25
Extracellular glutamate and IDH1R132H inhibitor promote glioma growth by boosting redox potential
Tiburcio, P. D. B., Gillespie, D. L., Jensen, R. L., & Huang, E. L. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-019-03359-w · Cited by 25
Illuminating the cross-talk between tumor metabolism and immunity in IDH-mutated cancers
Leca, J., Fortin, J., & Mak, T. W. (2020) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2020.11.013 · Cited by 23
Tang, H. R., Mirshahidi, S., Senthil, M., Kazanjian, K. K., Chen, C.-S., & Zhang, K. (2014) · Cancer Biomarkers · doi:10.3233/cbm-140409 · Cited by 24
“Multivariate statistical analysis using the “R” program has previously been utilized for metabolic profiling [35].”
Umelo, I. A., Costanza, B., & Castronovo, V. (2018) · Cancer and Metastasis Reviews · doi:10.1007/s10555-017-9710-0 · Cited by 23
“ed with a unique metabolic signature [104].”
Chitneni, S. K., Yan, H., & Zalutsky, M. R. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00478 · Cited by 24
Self-citationEarly Noninvasive Metabolic Biomarkers of Mutant IDH Inhibition in Glioma
Radoul, M., Hong, D., Gillespie, A. M., Najac, C., Viswanath, P., Pieper, R. O., Costello, J., Luchman, H. A., & Ronen, S. M. (2021) · Metabolites · doi:10.3390/metabo11020109 · Cited by 24
“The increase in Glu observed both in cells and in vivo reflects a reversal of metabolic changes previously reported to be associated with the IDH mutation by our group and others in cell models [37,44] and in patient samples [45].”
Branzoli, F., & Marjańska, M. (2020) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000833 · Cited by 23
“Illustration of IDH function change with indicate exchange of a metabolite between the cation [7].”
BackgroundInfluentialExploiting Metabolic Differences in Glioma Therapy
Galeffi, F., & Turner, D. A. (2012) · Current Drug Discovery Technologies · doi:10.2174/157016312803305906 · Cited by 23
“The other mitochondrial isoform of this enzyme (NADHdependent IDH 3) specifically catalyzes the oxidative decarboxylation of isocitrate to α-KG in the TCA cycle, and is critical for TCA cycle function [91].”
BackgroundKudryashova, T. V., Goncharov, D. A., Pena, A. Z., Ihida‐Stansbury, K., DeLisser, H. M., Kawut, S. M., & Goncharova, E. A. (2015) · Pulmonary Circulation · doi:10.1086/683810 · Cited by 23
“Metabolomic profiling was performed by Metabolon (Durham, NC), as previously described.(10) Briefly, cell pellets were subjected to a series of organic and aqueous extractions, divided into two fractions, frozen, and dried under vacuum, and liquid chromatography– and gas chromatography–based mass spectrometry were per…”
MethodGLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells
Santos-Jiménez, J. D. L., Campos-Sandoval, J. A., Alonso, F. J., Márquez, J., & Matés, J. M. (2024) · Antioxidants · doi:10.3390/antiox13060745 · Cited by 25
“…is considered an oncometabolite capable of inhibiting the branched-chain amino acid aminotransferases 1 and 2 (BCAT1/2), which use AKG and branched-chain amino acids as substrates to produce Glu and the corresponding branched-chain alpha-ketoacid, in a reversible amino group transfer reaction [78].”
Calvo, X., Nomdedéu, M., Navarro, A., Tejero, R., Costa, D., Muñoz, C., Pereira, A., Peña, O. D. R., Risueño, R. M., Monzó, M., et al. (2014) · Leukemia Research · doi:10.1016/j.leukres.2014.04.015 · Cited by 23
Duan, Y., Yu, J., Chen, M., Lu, Q., Ning, F., Gan, X., Liu, H., Ye, Y., Lu, S., & Lash, G. E. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-023-01156-8 · Cited by 22
“Isocitrate dehydrogenase mutations in cancer promote the development of a neomorphic enzyme that converts isocitrate into D-2-hydroxyglutarate, a metabolite with oncogenic effects and epigenetic regulation [42].”
BackgroundProgress on molecular biomarkers and classification of malignant gliomas
Zhang, C., Bao, Z., Zhang, W., & Jiang, T. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0267-1 · Cited by 21
MicroRNAs: Novel Mechanism Involved in the Pathogenesis of Microwave Exposure on Rats’ Hippocampus
Zhao, L., Sun, C., Xiong, L., Yang, Y., Gao, Y., Wang, L., Zuo, H., Xu, X., Dong, J., Zhou, H., et al. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0289-4 · Cited by 20
“Moreover, IDH1 and PDHB, which modulated tricarboxylic acid cycle and energy metabolism to regulate ischemia-induced hippocampal injury, were predicted as the targets of mir-181a (Prasad et al. 2011; Reitman et al. 2011).”
BackgroundExploration of the chondrosarcoma metabolome; the mTOR pathway as an important pro-survival pathway
Addie, R. D., de Jong, Y., Alberti, G., Kruisselbrink, A. B., Que, I., Baelde, H. J., & Bovée, J. V. M. G. (2019) · Journal of bone oncology · doi:10.1016/j.jbo.2019.100222 · Cited by 20
Clément, A., Zaragori, T., Filosa, R., Ovdiichuk, O. V., Beaumont, M., Collet, C., Roeder, E., Martin, B., Maskali, F., Barberi‐Heyob, M., et al. (2022) · Cancer Imaging · doi:10.1186/s40644-022-00454-6 · Cited by 19
“This IDH1 mutation leads to an intracytoplasmic accumulation of 2-hydroxyglutarate (2-HG) [5] which alters overall tumor metabolism [6].”
BackgroundLiu, Y., Wang, M., Guo, Y., Wang, L., & Guo, W. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112067 · Cited by 21
Zhu, J., Cui, G., Chen, M., Xu, Q., Wang, X., Zhou, D., Lv, S., Fu, L., Wang, Z., & Zuo, J. (2012) · Journal of Molecular Neuroscience · doi:10.1007/s12031-012-9890-6 · Cited by 20
“Our data were in line with the findings that mutant IDH1 expressing cells exhibited increases in acetyl-CoA and phospholipid precursors (Reitman et al. 2011).”
In vivo Metabolic Profiles as Determined by 31P and short TE 1H MR-Spectroscopy
Wenger, K. J., Hattingen, E., Franz, K., Steinbach, J. P., Bähr, O., & Pilatus, U. (2017) · Clinical Neuroradiology · doi:10.1007/s00062-017-0630-8 · Cited by 20
RNA-Binding Protein HuR Regulates Both Mutant and Wild-Type IDH1 in IDH1-Mutated Cancer
Zarei, M., Lal, S., Gohar, A. V., O’Hayer, K., Gunda, V., Singh, P. K., Brody, J. R., & Winter, J. M. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0557 · Cited by 20
“IDH1 should specifically diminish 2HG and glutamate levels (43, 44).”
BackgroundKatz, L., Tata, A., Woolman, M., & Zarrine‐Afsar, A. (2021) · Metabolites · doi:10.3390/metabo11100660 · Cited by 22
Liu, Y., Gilbert, M. R., Kyprianou, N., Rangnekar, V. M., & Horbinski, C. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1334-7 · Cited by 20
“1e, 2b–d) is within the range of what has been reported for endogenous mutant IDH1 gliomas in patients [18], and is also similar to that used by other groups [46].”
Chitneni, S. K., Reitman, Z. J., Gooden, D. M., Yan, H., & Zalutsky, M. R. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.04.066 · Cited by 20
“As a result, such detection assays, A C C E P T E D M A N U S C R I P T”
Self-citationCystathionine-γ-lyase drives antioxidant defense in cysteine-restricted IDH1-mutant astrocytomas
Cano-Galiano, A., Oudin, A., Fack, F., Allega, M. F., Sumpton, D. P., Martínez-García, E., Dittmar, G., Hau, A., Falco, A. D., Herold‐Mende, C. C., et al. (2021) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdab057 · Cited by 19
Hundal, B. K., Lutfi, E., Sigholt, T., Rosenlund, G., Liland, N. S., Glencross, B. D., & Sissener, N. H. (2022) · Metabolites · doi:10.3390/metabo12020159 · Cited by 19
“Analysis of metabolites was performed by Metabolon (Durham, NC, USA), as previously described [76,77], on liver samples collected from fish fed diets 1.”
MethodFalco, P. D., Lazzarino, G., Felice, F., Desideri, E., Castelli, S., Salvatori, I., Ciccarone, F., & Ciriolo, M. R. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102585 · Cited by 20
“Reduced levels of NAA were described in pancreatic cancer [48], IDH1-mutated gliomas [49], human and a mouse model of glioblastoma [50,51].”
BackgroundPrognostic role of mitochondrial pyruvate carrier in isocitrate dehydrogenase–mutant glioma
Karsy, M. J., Guan, J., & Huang, E. L. (2018) · Journal of neurosurgery · doi:10.3171/2017.9.jns172036 · Cited by 20
IDH1 mutation-associated long non-coding RNA expression profile changes in glioma
Zhang, X., Kiang, K. M. Y., Wang, Y., Pu, J. K.-S., Ho, A. S.-W., Cheng, S. Y., Lee, D., Zhang, P., Chen, J., Lui, W., et al. (2015) · Journal of Neuro-Oncology · doi:10.1007/s11060-015-1916-9 · Cited by 19
Grelli, K. N., Palubinsky, A. M., Kale, A. C., Lizama, B. N., Stankowski, J. N., Milne, G. L., Singer, R. J., & McLaughlin, B. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113129990062 · Cited by 18
“Though the mechanism of 2HG action is unclear, some have hypothesized that 2-HG plays a role in increasing ROS damage and competitively inhibiting metabolic enzymes including N-acetyl-aspartyl-glutamate [67, 68] and prolyl hydroxylases based on their structural similarity to α-KG [69].”
BackgroundLi, T., Cox, C. D., Ozer, B. H., Nguyen, N. T., Nguyen, H. N., Lai, T. J., Li, S., Liu, F., Kornblum, H. I., Liau, L. M., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0367 · Cited by 18
“IDH1 mutation causes multiple metabolic abnormalities independent of D-2-HG, such as inactivation of NADPH-dependent reductive carboxylation (40), stimulation of glutamine metabolism under hypoxia (41), inhibition of ATP synthase (42), and alteration of glutathione and TCA cycle metabolite levels (43).”
BackgroundFeng, S., & Liu, Y. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51652-9_18 · Cited by 18
Micro RNA ‐661 modulates redox and metabolic homeostasis in colon cancer
de Cedrón, M. G., Acín‐Pérez, R., Sánchez‐Martínez, R., Molina, S., Herránz, J., Feliú, J., Reglero, G., Enríquez, J. A., & de Molina, A. R. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12142 · Cited by 17
“DLD1-miR661 and DLD1-Control cells were prepared as indicated by Metabolon Inc. for global metabolomic analysis (Reitman et al., 2011).”
MethodZhou, Y., Wang, L., Wang, C., Wu, Y., Chen, D., & Lee, T. H. (2020) · Archives of Pharmacal Research · doi:10.1007/s12272-020-01205-6 · Cited by 19
Metadata
- Authors
- Reitman, Z. J., Jin, G., Karoly, E. D., Spasojevic, I., Yang, J., Kinzler, K. W., He, Y., Bigner, D. D., Vogelstein, B., & Yan, H.
- Affiliations
- Duke University (US)
- Metabolon (United States) (US)
- Duke Comprehensive Cancer Center,
- The Ludwig Center and
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-02-02
- Volume
- 108
- Issue
- 8
- Pages
- 3270-3275
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3044380
- OpenAlex
- W2171026968
- Cited by
- 449
- References
- 31
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 12 · 2023: 24 · 2022: 20 · 2021: 21 · 2020: 23 · 2019: 25 · 2018: 38 · 2017: 34 · 2016: 29 · 2015: 38 · 2014: 45 · 2013: 42 · 2012: 48
- FWCI
- 24.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Association for Cancer Research
- Pediatric Brain Tumor Foundation
- Virginia and D.K. Ludwig Fund for Cancer Research
- National Institutes of Health
- National Cancer Institute (CA43460, 5P30-CA-014236-36, R37CA043460, R01CA140316, P30CA014236)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- isocitrate dehydrogenase, IDH1 mutation, IDH2 mutation, 2-hydroxyglutarate, glioma, oligodendroglioma, N-acetylaspartylglutamate, glutathione metabolism, choline derivatives, TCA cycle intermediates, amino acids, cancer metabolism
- MeSH terms
- Dipeptides, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Mutation, Oligodendroglioma, Cell Line, Tumor, Metabolome
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