PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 31139406-3 2019 We hypothesized that inhibition of glutamate processing with the pleiotropic GLUD-inhibitor epigallocatechin-3-gallate (EGCG) would not only hamper D-2-HG production, but also decrease NAD(P)H and alpha-KG synthesis in IDH mut cancers, resulting in increased metabolic stress and increased sensitivity to radiotherapy. Glutamic Acid 35-44 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 219-222 31139406-6 2019 Results: Significant amounts of 13C from glutamate accumulate in D-2-HG in HCT116-IDH1 wt/R132H but not in HCT116-IDH1 wt/wt . Glutamic Acid 41-50 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 82-86 31139406-7 2019 Preventing glutamate processing in HCT116-IDH1 wt/R132H cells with EGCG resulted in reduction of D-2-HG production. Glutamic Acid 11-20 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-46 31139406-10 2019 Conclusions: This work shows that glutamate can be directly processed into D-2-HG and that reduction of glutamatolysis may be an effective and promising new treatment option for IDH mut cancers. Glutamic Acid 34-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 178-181 29662077-5 2018 Importantly, inhibition of mutant IDH1 may lead to the reprogramming of tumor metabolism, suggested by simultaneous changes in glutathione, glutamine, glutamate, and lactate. Glutamic Acid 151-160 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 29076421-3 2017 The epilepsy is related to elevated extracellular glutamate stimulating NMDAand AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Glutamic Acid 141-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 154-158 27154922-0 2016 Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. Glutamic Acid 20-29 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 93-97 27154922-8 2016 Interestingly, glutamate levels were significantly decreased in IDH1 mutant gliomas. Glutamic Acid 15-24 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 64-68 27154922-10 2016 Conventional MRS detection of glutamate and 2HG resulted in a high diagnostic accuracy (sensitivity 72%, specificity 96%) for IDH1 mutant glioma. Glutamic Acid 30-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 126-130 27154922-11 2016 CONCLUSIONS: IDH1 mutations alter glutamate metabolism. Glutamic Acid 34-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 27154922-12 2016 Combining glutamate levels optimizes the 2HG-based monitoring of IDH1 mutations via MRS and represents a reliable clinical application for diagnosing IDH1 mutant gliomas. Glutamic Acid 10-19 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 65-69 27154922-12 2016 Combining glutamate levels optimizes the 2HG-based monitoring of IDH1 mutations via MRS and represents a reliable clinical application for diagnosing IDH1 mutant gliomas. Glutamic Acid 10-19 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 150-154 24903073-3 2014 The IDH1 mutation leads to the accumulation of 2-hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. Glutamic Acid 130-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-8 26970248-6 2016 RESULTS: The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish alpha-ketoglutarate lost by conversion to 2HG. Glutamic Acid 262-271 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 138-141 26045167-6 2015 (13)C-MRS also revealed a reduction in glucose flux to glutamate in IDH1 mutant cells. Glutamic Acid 55-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 68-72 25706986-11 2015 Specifically, a significant drop in the concentration of glutamate, lactate and phosphocholine as well as the expected elevation in 2-hydroxyglutarate were observed in mutant IDH1 cells when compared to their wild-type counterparts. Glutamic Acid 57-66 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 175-179 26478444-2 2015 Presence of IDH1 mutation is frequently associated with seizures in oligodendrogliomas, next to alterations of glutamate and GABA metabolism in the origin of glioma-associated epilepsy. Glutamic Acid 111-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 25398942-0 2014 Response to "Tumor cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas". Glutamic Acid 39-48 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 107-111 25908561-2 2015 However, in isocitrate dehydrogenase (IDH)-mutant gliomas, (13)C labeling is obscured in oncometabolite 2-hydroxyglutaric acid (2 HG) by glutamate and glutamine, prompting development of a simple method to resolve the metabolites. Glutamic Acid 137-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-36 25908561-2 2015 However, in isocitrate dehydrogenase (IDH)-mutant gliomas, (13)C labeling is obscured in oncometabolite 2-hydroxyglutaric acid (2 HG) by glutamate and glutamine, prompting development of a simple method to resolve the metabolites. Glutamic Acid 137-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-41 25074540-0 2014 Tumor cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas. Glutamic Acid 26-35 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 94-98 25225364-3 2014 We report here that IDH1(R132H) exhibits a growth-inhibitory effect that is abrogated in the presence of glutamate dehydrogenase 2 (GLUD2), a hominoid-specific enzyme purportedly optimized to facilitate glutamate turnover in human forebrain. Glutamic Acid 105-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 25225364-8 2014 These findings suggest that specialization of human neocortex for high glutamate neurotransmitter flux creates a metabolic niche conducive to growth of IDH1 mutant tumors. Glutamic Acid 71-80 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 152-156 24590270-12 2014 Intriguingly, in gliomas with IDH1-R132H, glutamine and glutamate levels were significantly reduced which implies replenishment of alpha-KG by glutaminolysis. Glutamic Acid 56-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 24747768-8 2014 In this review we present a novel hypothesis which links IDH1 and IDH2 mutations to glutamate metabolism, possibly explaining the specific biological behavior of diffuse glioma. Glutamic Acid 84-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 57-61 24876103-9 2014 Hyperpolarized [1-(13)C] glutamate could thus inform on multiple mutant IDH1-associated metabolic events that mediate reduced glutamate production. Glutamic Acid 25-34 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 72-76 24876103-9 2014 Hyperpolarized [1-(13)C] glutamate could thus inform on multiple mutant IDH1-associated metabolic events that mediate reduced glutamate production. Glutamic Acid 126-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 72-76 32958546-0 2020 Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment. Glutamic Acid 0-9 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-54 23090985-7 2012 IDH1 mutant tumors demonstrated significantly reduced glutamate by in vivo MRS. Glutamic Acid 54-63 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 23090985-9 2012 The IDH1(R132) mutation results in 2-HG resonance at 2.25 ppm and a reduction of glutamate levels as determined by MRS. Our results establish a model system where 2-HG can be monitored noninvasively, which should be helpful in validating 2-HG levels as a prognostic and/or predictive biomarker in glioma. Glutamic Acid 81-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-13 35128264-2 2022 Subsequent studies led to the discovery of a panel of enzymes mainly involved in glutamate anaplerosis and aerobic glycolysis that change in abundance as a result of the IDH1 mutation. Glutamic Acid 81-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 170-174 35128264-6 2022 Results confirmed increased glutamate use and decreased aerobic glycolysis in resected IDH1 R132H glioma tissue samples. Glutamic Acid 28-37 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 87-91 11087384-5 2000 Random mutants targeted the IDH active site at positions 113 (substituted with glutamate), 115, and 116 (both randomized) and were screened for activity toward isopropylmalate. Glutamic Acid 79-88 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-31 34610989-2 2021 IDH1/2 mutations are thought to be associated with seizures owing to the structural similarity between D2HG and glutamate. Glutamic Acid 112-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 33846339-6 2021 However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamic Acid 34-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-64 32958546-9 2020 SIGNIFICANCE: These findings show that glutamate can be used as a noninvasive, imageable metabolic marker for early assessment of tumor response to temozolomide, with the potential to improve treatment strategies for mutant IDH1 patients. Glutamic Acid 39-48 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 224-228 31960518-4 2020 We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism, and the TCA cycle in IDH1 mut gliomas. Glutamic Acid 92-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 135-139 31960518-5 2020 Specifically, the enzymes involved in the metabolism of glutamate, lactate, and enzymes involved in the conversion of alpha-ketoglutarate were increased in IDH1 mut gliomas. Glutamic Acid 56-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 156-160 31960518-7 2020 We also found that enzymes that convert proline, valine, leucine, and isoleucine into glutamate were increased in IDH1 mut glioma. Glutamic Acid 86-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 114-118 31960518-8 2020 We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA-cycle activity in IDH1 mut gliomas. Glutamic Acid 90-99 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 31960518-8 2020 We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA-cycle activity in IDH1 mut gliomas. Glutamic Acid 90-99 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 135-139 31504231-6 2019 By taking into consideration a large body of findings in the literature, this article analyzes how different approaches have led to opposing conclusions and proffers a counterintuitive hypothesis that IDH1 mutation is intrinsically tumor suppressive in glioma but functionally undermined by the glutamate-rich cerebral environment, inactivation of tumor-suppressor genes and IDH1 copy-number alterations. Glutamic Acid 295-304 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 201-205