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. 2023 Sep 13;8:345. doi: 10.1038/s41392-023-01569-3

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© The Author(s) 2023

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Glutamine and BCAA metabolism. BCAAs can be absorbed by the cell through L-type amino acid transporter (LATs), and L-type amino acid transporter 1(LAT1) can also exchange intracellular glutamine with extracellular leucine. In cells, BCAAs are catalyzed to formα-ketoisocaproate (KIC), α-ketoisovalerate (KIV), and α-keto-β-methylvalerate (KMV). The three substances are collectively known as branched alpha-ketoacids (BCKAs). Further, BCKAs produce acetyl-CoA through an irreversible rate-limiting reaction catalyzed by branched alpha-ketoate dehydrogenase (BCKDH) and subsequent reactions. Acetyl-CoA may be involved in the TCA cycle or other amino acid synthesis. Glutamine can be transported by SLC1A5 (ASCT2), LAT1 (L-type amino acid transporter), and xCT (SLC7A11). Glutamine is involved in glutathione (GSH) synthesis and cell REDOX homeostasis regulation in cytoplasm. In the mitochondria, glutamine produces Glutamate through a reaction catalyzed by glutaminase (GLS), which participates in the TCA cycle by producing α-KG by aminotransferase (ATs) and Glutamate dehydrogenase (GLUD). Created with BioRender.com. (The red blunt line represents inhibition)