Chapter 12 - Relationship between Arginase Activity and Nitric Oxide Production

Abstract

Nitric oxide (NO) is synthesized from arginine by NO synthase (NOS), and the availability of arginine is one of the rate-limiting factors in cellular NO production. Arginase catalyzes the hydrolysis of arginine to urea and ornithine. Thus, both NOS and arginase use arginine as a common substrate. Arginase exists in two known isoforms, hepatic cytosolic type (arginase I) and nonhepatic mitochondrial Type (arginase II). Several lines of evidence indicate that arginase competes with NOS for the substrate and downregulates NO production. Inducible NOS (iNOS) and arginase activities are regulated reciprocally in macrophages by cytokines, and this may guarantee the efficient production of NO. When rat peritoneal macrophages are stimulated with bacterial lipopolysaccharide (LPS), iNOS is induced first, followed by arginase I, suggesting that arginase I prevents sustained overproduction of NO. On the other hand, no production in activated macrophages is enhanced by arginase inhibitors. When arginase II is induced, NO production is much decreased, and the cells are rescued from apoptosis. The results indicate that NO production is modulated by arginase isoforms at the level of both activity and enzyme amount in various cell types.