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. 2021 Jul 22;53(8):1169–1179. doi: 10.1007/s00726-021-03052-1

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — The role of glutamine in cancer. Glutamine enables rapidly proliferating cells to meet increased energy demands in addition to its utilisation in protein synthesis. Glutamine enters the cell via the amino acid transporter SLC1A5 and is converted to glutamate in the mitochondria via a deamination reaction catalysed by GLS. Glutamate is further converted to the TCA cycle intermediate α-ketoglutarate. α-ketoglutarate is a critical metabolite involved in both ATP production and replenishing TCA cycle intermediates (anaplerosis). Cytosolic glutamate is critical for maintaining redox homeostasis through the production of GSH which protects against oxidative stress. Glutamine efflux via the SLC7A5 amino acid transporter allows leucine to enter the cell and activate mTORC1-mediated cell growth. Abbreviations: AST aspartate transaminase; ATP adenosine triphosphate; GDH glutamate dehydrogenase; GLS glutaminase; GSH S-glutathione; mTORC1 mammalian target of rapamycin complex 1; NADP ± nicotinamide adenine dinucleotide phosphate; RAS rat sarcoma GTPase; SLC1A5 solute carrier family 1 member 5; SLC7A5 solute carrier family 7 member 5; TCA tricarboxylic acid. Adapted in Biorender from Choi and Park (2018); Hensley et al. (2013); Martinez-Outschoorn et al. (2017)