Glutamine-utilizing metabolic enzymes

Glutamine-utilizing metabolic enzymes represent a diverse group of enzymes that utilize glutamine as a nitrogen donor for the biosynthesis of essential cellular components, including nucleotides, amino acids, and hexosamines (ResearchGate, 2025). Key members of this class include glutaminase (GLS), which initiates glutaminolysis, and various amidotransferases such as phosphoribosylpyrophosphate amidotransferase (PPAT) and asparagine synthetase (ASNS) (NIH, 2020). In many malignancies, cancer cells exhibit 'glutamine addiction,' where they rely heavily on these enzymes to support rapid proliferation, energy production, and redox homeostasis (Frontiers in Oncology, 2024). Consequently, these enzymes have become significant therapeutic targets in oncology. Broad-spectrum glutamine antagonists, such as 6-diazo-5-oxo-L-norleucine (DON), inhibit multiple enzymes within this class simultaneously, though their clinical utility has historically been limited by systemic toxicities (NIH, 2019). Recent drug development efforts focus on more selective inhibitors, such as telaglenastat for GLS, or tumor-targeted prodrugs like sirpiglenastat to improve the therapeutic index (Johns Hopkins, 2019). Monitoring biomarkers like GLS expression or MYC amplification can help identify patients most likely to benefit from these metabolic interventions.

Other names

Glutamine-utilizing metabolic enzymes – general metabolismGlutamine-dependent enzymesGlutamine amidotransferasesGlutamine-utilizing enzymesGlutamine-dependent metabolic enzymes

Inhibition of glutamine-dependent biosynthetic pathways by acting as glutamine mimetics or competitive inhibitors, thereby depleting essential metabolites like nucleotides and glutamate.