Arginine Depletion (Arg Depletion)

Arginine depletion refers to the reduction or elimination of arginine levels in the cellular environment. This strategy is employed therapeutically to target cancers that are auxotrophic for arginine, meaning they cannot synthesize it themselves and rely on external sources. Arginine depletion can be achieved through enzymatic degradation using agents like ADI-PEG20 or arginases. In genetic disorders like arginase deficiency, impaired arginine metabolism leads to hyperammonemia and neurological complications. Arginine depletion affects several key pathways, including protein synthesis, nitric oxide production, the urea cycle, and polyamine synthesis, and suppresses T-cell function.

Other names

Arginine StarvationArginine RestrictionArginine Metabolism Inhibition

Enzymatic degradation of extracellular arginine, leading to depletion of intracellular arginine pools in arginine auxotrophic cells. This induces autophagy and apoptosis in cancer cells lacking the ability to synthesize arginine endogenously. In arginase deficiency, accumulation of arginine and ammonia leads to neurological dysfunction.