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

Glutamate and α-ketoglutarate: key players in glioma metabolism.

Author information

1
Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
2
University of Gottingen, Gottingen, Germany.
3
Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. gj.peters@vumc.nl.

Abstract

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

PMID:
27752843
PMCID:
PMC5241329
DOI:
10.1007/s00726-016-2342-9
[Indexed for MEDLINE]
Free PMC Article

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