Arginase-2, mitochondrial (ARG2) (ARG2)

Arginase-2 (ARG2) is a mitochondrial enzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea (UniProt, PubMed). Unlike its cytosolic counterpart Arginase-1, which is central to the hepatic urea cycle, ARG2 is widely distributed in extrahepatic tissues such as the kidney, prostate, and vascular endothelium (NCBI, PMC). It plays a critical role in regulating L-arginine bioavailability, thereby competing with nitric oxide synthase (NOS) and limiting the production of nitric oxide (NO) (UniProt, PMC). In oncology, ARG2 is frequently overexpressed in the tumor microenvironment, causing local arginine depletion that suppresses T-cell activation and promotes immune evasion (PubMed, PMC). In cardiovascular and metabolic contexts, its upregulation is associated with endothelial dysfunction, oxidative stress, and vascular aging (PMC). Therapeutic development focuses on small-molecule inhibitors, including dual ARG1/ARG2 inhibitors like Numidargistat and OATD-02, aimed at restoring arginine levels to enhance anti-tumor immunity or improve vascular health (PubMed, Patsnap Synapse).

Other names

Arginase IIKidney-type arginaseNon-hepatic arginaseType II arginaseL-arginine amidinohydrolaseL-arginine ureahydrolase

Competitive inhibition of arginase activity to increase L-arginine bioavailability for nitric oxide production or T-cell activation (PubMed, PMC).