Asparagine synthetase (glutamine-hydrolyzing) (ASNS)

Asparagine synthetase (glutamine-hydrolyzing), abbreviated ASNS, is an enzyme that catalyzes the ATP-dependent conversion of aspartate and glutamine to asparagine and glutamate, playing a central role in amino acid metabolism. ASNS is essential for supplying asparagine for cellular needs, especially for protein biosynthesis and N-linked glycosylation. The reaction occurs via two domains: the N-terminal domain hydrolyzes glutamine to produce ammonia, which is then channeled to the C-terminal synthetase domain for the formation of asparagine from aspartate. In humans, ASNS is the sole source of asparagine synthesis in the brain due to the inability of asparagine to cross the blood-brain barrier. Clinical significance includes ASNS deficiency, resulting in severe neurodevelopmental disorders, and its role as a cancer target, as many tumor cells depend on asparagine to proliferate and survive. Pharmacologically, ASNS is targeted indirectly by L-asparaginase in leukemia and by direct inhibitors in preclinical cancer therapy development. ASNS expression also serves as a biomarker for therapy selection and resistance.

Other names

Asparagine synthetase BGlutamine-dependent asparagine synthetaseASAS-BL-aspartate:L-glutamine amido-ligase (AMP-forming)

Competitive inhibition of the ASNS enzyme active site (for ASNS inhibitors). Depletion of asparagine levels (by L-asparaginase, exploits tumor reliance on asparagine synthesis).