Asparagine synthetase [glutamine-hydrolyzing]

Asparagine synthetase [glutamine-hydrolyzing] (ASNS) is a metabolic enzyme that catalyzes the ATP-dependent synthesis of asparagine from aspartate and glutamine, playing a central role in amino acid biosynthesis (UniProt: P08243). The protein is widely distributed across tissues and is particularly important in cells with high biosynthetic demands. Mutations in ASNS cause asparagine synthetase deficiency (ASNSD; MIM 615574), a rare inborn error of metabolism characterized by severe neurologic manifestations including microcephaly, developmental delay, progressive encephalopathy, and seizures (UniProt: P08243).

In Alzheimer's disease, ASNS expression is significantly reduced in human post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change −0.53; Chaparral AD proteomics). This downregulation was observed in TMT-labeled quantitative proteomics analysis across multiple subcellular fractions, suggesting decreased asparagine biosynthetic capacity in the diseased brain. The reduced ASNS levels may reflect broader metabolic dysregulation characteristic of neurodegeneration, although the functional consequences of diminished asparagine synthesis in AD pathogenesis remain to be clarified.