Arginase

Arginase is a metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The reaction consumes water and releases urea, a key step in nitrogen disposal. Arginase is manganese-dependent; the active site contains binuclear Mn2+ centers essential for catalysis.

Two mammalian isozymes exist: Arginase I, a cytosolic enzyme predominantly expressed in the liver as part of the urea cycle, and Arginase II, a mitochondrial enzyme with broader tissue distribution including kidney, brain, and adipose tissue. Both are typically trimeric metalloenzymes and require Mn2+ for activity.

Biologically, arginase provides ornithine for the biosynthesis of polyamines and proline, linking arginine catabolism to multiple metabolic pathways. It also regulates intracellular arginine availability, and thereby modulates nitric oxide production by competing with nitric oxide synthase for arginine, influencing vascular tone and immune responses. In macrophages, arginase expression can be linked to different activation states and inflammatory conditions.

Clinical relevance: inherited deficiency of arginase I causes hyperargininemia, a urea cycle disorder characterized by elevated arginine and progressive neurological symptoms, hyperammonemia, and spasticity. Management includes protein restriction, ammonia scavengers, and, in severe cases, liver transplantation. Arginase activity is also a target in biomedical research: inhibitors of arginase are studied to boost nitric oxide production or to alter polyamine synthesis in cancer and parasitic infections, while in some contexts enhancing arginase activity may support tissue repair or regulate immune responses.