Glutaminase kidney isoform, mitochondrial (GLS1) (GLS1)

Glutaminase kidney isoform, mitochondrial (GLS1) is an enzyme that catalyzes the conversion of L-glutamine to L-glutamate and ammonia, serving as the first and rate-limiting step in glutaminolysis (UniProt P13264). This pathway is critical for providing carbon and nitrogen sources for the tricarboxylic acid (TCA) cycle, nucleotide biosynthesis, and the production of glutathione, an essential antioxidant (PubMed: 28844002). Many cancer cells exhibit "glutamine addiction," overexpressing GLS1 to support rapid proliferation and survival under metabolic stress (PubMed: 30694570). Consequently, GLS1 has emerged as a significant therapeutic target in oncology, with small-molecule inhibitors like Telaglenastat (CB-839) being evaluated in clinical trials for various solid tumors and hematologic malignancies (ClinicalTrials.gov: NCT02071888). Inhibition of GLS1 aims to starve tumor cells of essential nutrients, leading to growth arrest and increased sensitivity to oxidative stress and other chemotherapeutic agents.

Other names

GLSK-type glutaminaseKidney-type glutaminaseGLS1Glutaminase kidney isoform, mitochondrialL-glutamine amidohydrolase

Allosteric inhibition of the glutaminase enzyme, which prevents the conversion of glutamine to glutamate, thereby disrupting the tricarboxylic acid (TCA) cycle and glutathione synthesis in cancer cells.