Other glutamine-utilizing enzymes

Other glutamine-utilizing enzymes is a collective term for a group of enzymes, primarily glutamine amidotransferases, that utilize the amide nitrogen of glutamine for various biosynthetic processes. This group includes critical enzymes such as CTP synthase (CTPS), asparagine synthetase (ASNS), and amidophosphoribosyltransferase (PPAT), which are essential for the synthesis of nucleotides, amino acids, and amino sugars. In many cancers, these pathways are upregulated to support rapid cell proliferation, a phenomenon known as glutamine addiction. While glutaminase (GLS) is the most well-known target in this pathway, other enzymes in the group are also vital for tumor survival and metabolic plasticity. Broad-spectrum glutamine antagonists, such as 6-diazo-5-oxo-L-norleucine (DON) and its prodrugs (e.g., JHU-083), act by irreversibly binding to the conserved glutamine-binding domains of these enzymes. However, the lack of selectivity often leads to significant systemic toxicities, particularly in the gastrointestinal tract and bone marrow, which has historically limited their clinical development.

Other names

Glutamine amidotransferasesGlutamine-dependent enzymesPan-glutamine targets

Irreversible competitive inhibition of glutamine-binding sites in multiple amidotransferases.