Role of Glutamine in Cancer: Therapeutic and Imaging Implications

Glutamine metabolism in cancer cells and its regulation by oncogenes and tumor suppressors. After glutamine is imported into cell through surface transporters such as ASCT1 or SN2, most of it either donates nitrogen to macromolecules or is deamidated by glutaminases, which remove γ-nitrogen to form glutamate (Glu). Glu can be used for biosynthesis of glutathione (GSH) or processed further in mitochondria, where removal of α-nitrogen by aminotransferases or glutamate dehydrogenase (GDH) produces α-ketoglutarate (α-KG). Expression of glutaminases (GLS, GLS2) is upregulated by c-Myc and p53, respectively. Expression of glutamine synthetase (GS) is driven by β-catenin (β-cat). Ac-CoA = acetyl-coenzyme A; ALT = alanine aminotransferase; AST = aspartate aminotransferase; Cit = citrate; OAA = oxaloacetate; Pyr = pyruvate; TCA = tricarboxylic acid.