fig1

Figure 1. Different uses of glutamine in cancer cells. Glutamine enters the cells through transporters such as SLC1A5. Once inside the cell, glutamine can contribute to nucleotide biosynthesis directly (through CAD for example) or is converted to glutamate by GLS. Moreover, it can also be exported outside of the cell for the import of leucine, a coactivator of GDH. Then, glutamate can be converted to α-KG by GDH. Glutamate can contribute to the synthesis of glutathione through the activity of different enzymes, such as GCL. Amino acid synthesis is supported by the aminotransferases (such as GOT) which converts glutamate to α-KG. Glutamine-derived α-KG can enter the TCA cycle to produce energy for the cell or proceed backwards via the reductive carboxylation to provide an alternative source of lipid synthesis. Moreover, α-KG is a co-substrate of dioxygenase enzymes (such as JHMD and TED) in the regulation of histone and DNA methylation. α-KG: α-ketoglutarate; CAD: carbamoyl-phosphate synthetase 2 aspartate transcarbamylase, and dihydroorotase; CTP: CTP synthetase; GCL: glutamate-cysteine ligase; GLS: glutaminase; GDH: glutamate dehydrogenase; GOT: glutamate-oxaloacetate transaminase; JHMD: Jumonji C histone demethylases; TED: TET DNA demethylases