Glutamate and α-ketoglutarate: key players in glioma metabolism

Amino Acids. 2017 Jan;49(1):21-32. doi: 10.1007/s00726-016-2342-9. Epub 2016 Oct 17.


Glioblastoma multiforme (GBM), or grade IV astrocytoma, is the most common type of primary brain tumor. It has a devastating prognosis with a 2-year-overall survival rate of only 26 % after standard treatment, which includes surgery, radiation, and adjuvant chemotherapy with temozolomide. Also lower grade gliomas are difficult to treat, because they diffusely spread into the brain, where extensive removal of tissue is critical. Better understanding of the cancer's biology is a key for the development of more effective therapy approaches. The discovery of isocitrate dehydrogenase (IDH) mutations in leukemia and glioma drew attention to specific metabolic aberrations in IDH-mutant gliomas. In the center of the metabolic alterations is α-ketoglutarate (αKG), an intermediate metabolite in the tricarboxylic acid (TCA) cycle, and the associated amino acid glutamate (Glu). This article highlights the role of these metabolites in glioma energy and lipid production and indicates possible weak spots of IDH-mutant and IDH-wt gliomas.

Keywords: Alpha-ketoglutarate; Branched chain amino acids; Glioma; Glutamate; Isocitrate dehydrogenase.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Citric Acid Cycle / genetics
  • Gene Expression
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glutamic Acid / metabolism*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism*
  • Ketoglutaric Acids / metabolism*
  • Mutation
  • Neoplasm Grading
  • Reactive Oxygen Species / metabolism


  • Antimetabolites, Antineoplastic
  • Ketoglutaric Acids
  • Reactive Oxygen Species
  • Glutamic Acid
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human