Glutaminase (GLS) (GLS)

Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the hydrolysis of glutamine to glutamate and ammonia, serving as the rate-limiting step in glutaminolysis (UniProt: P13264). This metabolic pathway is frequently hijacked by cancer cells to support increased demands for energy, biosynthetic precursors, and antioxidant defense, a phenomenon often driven by the MYC oncogene (PubMed: 28841471). By converting glutamine into glutamate, GLS provides carbon skeletons for the tricarboxylic acid (TCA) cycle and nitrogen for nucleotide and amino acid synthesis (PubMed: 30622360). Therapeutic strategies focus on small-molecule allosteric inhibitors, such as Telaglenastat (CB-839), which aim to disrupt tumor metabolism and sensitize cells to other therapies (PubChem: 71725101). However, because glutamate is also a key neurotransmitter, the safety profile of these inhibitors must be carefully monitored for potential neurological side effects (PubMed: 31534017).

Other names

GLS1K-type glutaminaseKidney-type glutaminaseL-glutamine amidohydrolase (EC 3.5.1.2)GLS

Allosteric inhibition of the glutaminase enzyme, preventing the conversion of glutamine to glutamate and thereby disrupting the metabolic pathways essential for cancer cell proliferation and survival (PubMed: 28841471).