Glutamine-utilizing enzymes involved in nucleotide synthesis

Glutamine-utilizing enzymes are central to nitrogen assimilation and nucleotide biosynthesis, with Glutamine synthetase acting as the main enzyme catalyzing the ATP-dependent conversion of glutamate and ammonia to glutamine[1][5][6]. Glutamine, as a key nitrogen donor, is then required as a substrate for multiple steps in both purine and pyrimidine biosynthesis[2][4]. Cancer cells often rely on increased glutamine utilization to support rapid nucleotide and amino acid synthesis, making these enzymes attractive drug targets[2][7]. In humans, malfunction or dysregulation of GS impacts liver function, contributes to the pathogenesis of neurological diseases, and drives metabolic changes in tumors[3]. Inhibitors of these enzymes have been developed for cancer treatment and as herbicides, but safety is a major concern due to their ubiquity and essential metabolic functions[7].

Other names

Glutamine synthetaseGlutaminaseCarbamoyl-phosphate synthetaseGSGLSAmidotransferases

Active site inhibition (orthosteric inhibition—blocking substrate binding); Modulation of oligomeric states (experimental); Interference with regulatory loops affecting enzyme activity; Covalent inhibition (some herbicides)