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 mu M) 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. (C) 1994 Academic Press, Inc.