Abstract
The most common malignant brain tumors are those of astrocytic origin, gliomas, with the most aggressive glioblastoma (WHO grade IV) among them. Despite efforts, medicine has not made progress in terms of the prognosis and life expectancy of glioma patients. Behind the malignant phenotype of gliomas lies multiple genetic mutations leading to reprogramming of their metabolism, which gives those highly proliferating cells an advantage over healthy ones. The so-called glutamine addiction is a metabolic adaptation that supplements oxidative glycolysis in order to secure neoplastic cells with nutrients and energy in unfavorable conditions of hypoxia. The present review aims at presenting the research and clinical attempts targeting the different metabolic pathways involved in glutamine metabolism in gliomas. A brief description of the biochemistry of glutamine transport, synthesis, and glutaminolysis, etc. will forego a detailed comparison of the therapeutic strategies undertaken to inhibit glutamine utilization by gliomas.
Highlights
The metabolism of neoplasms has evolved to meet the demands of their high proliferative activity and growth in adverse conditions of hypoxia, nutrient shortage, and immunological pressure of the host
Both of those metabolic aberrations are present in gliomas [3,4,5], and are coupled [6,7], the present review focuses on glutamine addiction, and the Warburg effect will not be discussed
2-HG production from glutamine-derived α-KG and increased citrate production from the tricarboxylic acid (TCA) cycle. These results revealed that GLUD2 promotes the growth of IDH1R132H glioma cells in a manner that is not duplicated by overexpression of GLUD1 [121]
Summary
The metabolism of neoplasms has evolved to meet the demands of their high proliferative activity and growth in adverse conditions of hypoxia, nutrient shortage, and immunological pressure of the host. The reprogrammed metabolism of neoplasms, eventually adapting them to specific growth requirements and conditions, involves addiction to glucose (the Warburg effect, oxidative glycolysis) and/or glutamine. High but energetically futile glycolytic rates cannot compensate for high ATP demands; neoplasms, including gliomas, generate it via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation [1,2]. Both of those metabolic aberrations are present in gliomas [3,4,5], and are coupled [6,7], the present review focuses on glutamine addiction, and the Warburg effect will not be discussed
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