Fig. 6.

Metabolic reprogramming in brain cancer cell as compared with the normal cell. Brain tumor cell depends on glycolysis for glucose oxidation instead of oxidative phosphorylation and uses more glutamine. Cancer cells predominantly convert glucose into lactate even in the abundance of oxygen; this is referred to as aerobic glycolysis or the Warburg effect. The lactate aids in acidifying the tumor microenvironment and endorses invasion. Glioma cells also utilize glutamine as a substrate to enter the TCA involving IDH. Mutation of the IDH gene potentiates the formation of oncogenic 2-HG from α-KG. The metabolic reprogramming is executed by activation suppression of several transcription factors. Red arrows indicate downstream events and red lines indicate inhibition. 2-HG, 2-hydroxyglutarate; Akt, protein kinase B; ATP, adenosine triphosphate; HIF-1α, hypoxia-inducible factor 1-alpha; HK2, hexokinase 2; HK2, hexokinase 2; IDH, isocitrate dehydrogenase; LDH5, lactate dehydrogenase 5; LDHA, lactate dehydrogenase A; mTOR, mammalian target of rapamycin; PDK1, pyruvate dehydrogenase kinase 1; PI3K, phosphatidylinositide 3-kinases; PTEN, phosphatase and tensin homolog; TCA, tricarboxylic acid; VEGF, vascular endothelial growth factor; α-KG, α-ketoglutarate