L-glutamine metabolism

L-glutamine metabolism is a complex biochemical process involving the synthesis, transport, and catabolism of the amino acid glutamine, which serves as a critical nutrient for both healthy and malignant cells. In the context of oncology, many tumors exhibit "glutamine addiction," where they overexpress transporters like SLC1A5 and enzymes like glutaminase (GLS) to fuel the tricarboxylic acid (TCA) cycle and support rapid biosynthesis (Altman et al., 2016, PMID: 26890604). This pathway is also essential for maintaining redox balance through the production of glutathione, protecting cells from oxidative stress (Matés et al., 2019, PMID: 31103743). Therapeutic strategies targeting L-glutamine metabolism include small-molecule inhibitors of GLS, such as telaglenastat, and inhibitors of glutamine transporters or downstream enzymes (Cluntun et al., 2017, PMID: 28856334). However, because glutamine is a precursor for the neurotransmitter glutamate and is vital for T-cell activation, systemic inhibition of this pathway poses risks of neurotoxicity and immunosuppression (Jin et al., 2016, PMID: 26751371). Consequently, drug development in this area requires careful consideration of the therapeutic window and potential for metabolic compensation by cancer cells.

Other names

GlutaminolysisGlutamine metabolic pathwayGlutamine-glutamate cycle

Inhibition of glutaminase (GLS1) activity; Blockade of neutral amino acid transporter SLC1A5; Competitive inhibition of glutamine-dependent amidotransferases.