Glutamine-utilizing metabolic enzyme

Glutamine-utilizing metabolic enzymes are a functional class of proteins responsible for the processing and utilization of glutamine in various biosynthetic and bioenergetic pathways. The most prominent member of this group is glutaminase (GLS), which converts glutamine into glutamate to fuel the tricarboxylic acid (TCA) cycle and support the production of the antioxidant glutathione [1, 2]. Other members include glutamine-dependent amidotransferases, which are essential for the de novo synthesis of purine and pyrimidine nucleotides [3]. Many cancer types exhibit an increased reliance on these enzymes, a state often referred to as "glutamine addiction," which is frequently driven by the MYC oncogene [1]. Consequently, these enzymes are targeted by therapeutic agents such as the GLS inhibitor telaglenastat and the pan-glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) [3, 4]. Clinical development of these inhibitors must account for potential safety concerns, including neurotoxicity and gastrointestinal effects, given the vital role of glutamine in the central nervous system and systemic nitrogen balance [2, 3]. Monitoring biomarkers such as GLS expression levels and MYC status is often employed to identify patients most likely to benefit from these therapies [1, 4].

Other names

Glutamine metabolic enzymesGlutaminolysis enzymesGlutamine-dependent enzymesGlutamine amidotransferases

Inhibition of glutaminase activity to prevent glutaminolysis or competitive inhibition of glutamine-dependent amidotransferases to block nucleotide and amino acid biosynthesis [1, 3].