Arginase I (ARG1)

Arginase I is an enzyme primarily expressed in the liver cytoplasm where it catalyzes the final step of the urea cycle—hydrolyzing L–arginine into urea and ornithine. It is a trimeric binuclear manganese metalloenzyme with high substrate specificity. Beyond its metabolic role, Arginase I modulates immune function by depleting extracellular L–arginine—a mechanism exploited by certain myeloid-derived suppressor cells (MDSCs) to suppress T cell proliferation within tumor microenvironments. Elevated expression or activity has been implicated in various diseases including cancer-associated immunosuppression, chronic inflammation, infection response modulation, and fibrotic disorders. Several small-molecule inhibitors targeting its active site are under investigation for their potential to restore anti-tumor immunity or treat metabolic dysfunctions related to aberrant arginine metabolism.

Other names

Arginase-1Liver-type arginaseType I arginase

Competitive inhibition at the active site by substrate analogues or transition-state mimics that block conversion of L–arginine to urea and ornithine. Inhibition leads to increased availability of L–arginine for nitric oxide synthases, enhancing immune responses or reversing immunosuppression in cancer microenvironments