Arginase-2, mitochondrial (Arginase II (ARG2))

Arginase-2, mitochondrial is a manganese-dependent hydrolase located principally in mitochondria. Unlike cytosolic arginase I, which drives the hepatic urea cycle, arginase-2 has a broader tissue distribution (notably kidney, immune cells, vascular endothelium), and is crucial for extrahepatic arginine metabolism. By regulating local arginine availability, it competes with nitric oxide synthase, influencing production of NO and thereby impacting immune responses, vascular tone, and cell survival. Dysregulated arginase-2 activity fosters immunosuppressive environments (notably in tumors), exacerbates cardiac aging and inflammation, and influences systemic metabolic processes. Emerging therapeutic strategies target arginase-2 to reverse immune suppression in cancer, abate inflammation, and address metabolic and cardiovascular disorders. Inhibitors like C0021158 modulate enzyme activity via allosteric mechanisms, restoring T cell function and anti-tumor immunity.

Other names

Arginase IIKidney-type arginaseNon-hepatic arginaseType II arginaseAII type II arginaseMitochondrial arginase

Enzymatic inhibition (competitive or noncompetitive, including allosteric inhibitors like C0021158) Allosteric modulation leading to conformational changes that impair substrate binding and enzyme activity Restoration of T cell proliferation by reversing immunosuppression Indirect modulation of NO production and vascular/immune effects