Asparagine depletion

Asparagine depletion is a therapeutic strategy and cellular condition whereby the amino acid asparagine is removed or rendered unavailable, either through dietary restriction or drug intervention (most commonly with L-asparaginase). Asparagine is a nonessential amino acid for humans but can be essential for certain cancer cells (such as acute lymphoblastic leukemia) lacking sufficient asparagine synthetase (ASNS) activity; these cells depend on external asparagine and undergo apoptosis if deprived. Depletion of asparagine can modulate metabolic stress responses, enhance or impair immune cell function (notably T cell activation and effector activities), and trigger adaptations including activation of the integrated stress response via ATF4 and changes in mitochondrial function. Disease applications include cancer therapy and investigation into metabolic vulnerabilities of infection and rare metabolic diseases (such as ASNS deficiency). Asparagine depletion is not a discrete molecular target (e.g., receptor, enzyme, transporter) but a metabolic state, making it an unconventional therapeutic target; this is an important caveat when mapping structured data about drug targets.

Other names

Asparagine deprivationAsn depletionAsparagine restriction

Enzymatic depletion of extracellular asparagine, leading to suppression of protein synthesis and induction of apoptosis in cells unable to synthesize asparagine