Glutamine-dependent cellular metabolism

Glutamine-dependent cellular metabolism, primarily known as glutaminolysis, is a series of biochemical reactions where the amino acid glutamine is deaminated to glutamate and further converted into alpha-ketoglutarate to enter the tricarboxylic acid (TCA) cycle (Altman et al., 2016, Nature Reviews Cancer). This pathway serves as a crucial source of carbon and nitrogen for the biosynthesis of nucleotides, amino acids, and glutathione, which maintains cellular redox balance (Jin et al., 2023, Signal Transduction and Targeted Therapy). In many malignant tumors, oncogenic drivers like MYC upregulate this pathway, leading to a state of "glutamine addiction" where cells rely on high levels of glutamine for proliferation and survival (Cluntun et al., 2017, Annual Review of Cancer Biology). Pharmacological intervention typically targets specific nodes within this metabolism, such as the enzyme glutaminase (GLS) or transporters like SLC1A5 (ASCT2) (Jin et al., 2023, Signal Transduction and Targeted Therapy). While drugs like Telaglenastat have entered clinical trials, challenges remain regarding the potential for systemic toxicity, particularly affecting the central nervous system and the immune response, as glutamine is vital for T-cell activation and neurotransmitter synthesis (Altman et al., 2016, Nature Reviews Cancer).

Other names

GlutaminolysisGlutamine metabolismGln metabolismGlutamine-dependent pathway

Inhibition of glutaminase (GLS) enzymes, blockade of glutamine transporters (e.g., SLC1A5/ASCT2), or competitive antagonism of glutamine-utilizing enzymes to disrupt carbon and nitrogen supply in proliferating cells.