Metabolism of Glioblastoma

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The IDH1 gene encodes for the enzyme isocitrate dehydrogenase 1 and is uncommonly mutated in glioblastoma (number one GBM: 5%, secondary GBM >80%). By generating very high concentrations of the "oncometabolite" D-2-hydroxyglutarate and dysregulating the characteristic of the wild-kind IDH1 enzyme, it induces profound changes to the metabolism of IDH1-mutated glioblastoma, as compared with IDH1 wild-kind glioblastoma or healthful astrocytes. Among others, it increases the glioblastoma cells' dependence on glutamine or glutamate as an strength supply. IDH1-mutated glioblastomas are notion to have a very high call for for glutamate and use this amino acid and neurotransmitter as a chemotactic sign. Since healthful astrocytes excrete glutamate, IDH1-mutated glioblastoma cells do not favor dense tumor structures, but as a substitute migrate, invade, and disperse into healthful parts of the brain where glutamate concentrations are better. This may additionally provide an explanation for the invasive conduct of those IDH1-mutated glioblastoma.