Inhibition of rat liver arginase by an intermediate in NO biosynthesis, N(G)-hydroxy-L-arginine: Implications for the regulation of nitric oxide biosynthesis by arginase

N(G)-hydroxy-L-arginine, an intermediate in the biosynthesis of nitric oxide (NO), has been found to be a uniquely potent competitive inhibitor of rat liver arginase. Among previously reported inhibitors of arginase and the eight arginine analogs tested herein, only N(G)-hydroxy-L-arginine was found to be strongly inhibitory. Significantly, the K(i) (42 μM) for inhibition of rat liver arginase by N(G)-hydroxy-L-arginine was found to be 20-40-fold lower than the K(M) (1-1.7 mM) for its natural substrate, L-arginine. Since N(G)-hydroxy-L-arginine is the only known intermediate in the biosynthesis of NO from L-arginine, this finding may have significant implications for the regulation of NO levels in tissues or cells, such as liver or macrophages, which synthesize both NO and contain arginase.