Inhibition of rat liver arginase by an intermediate in NO biosynthesis, NG-hydroxy-L-arginine: implications for the regulation of nitric oxide biosynthesis by arginase.
NG-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 NG-hydroxy-L-arginine was found to be strongly inhibitory. Significantly, the Ki (42 microM) for inhibition of rat liver arginase by NG-hydroxy-L-arginine was found to be 20-40-fold lower than the KM (1-1.7 mM) for its natural substrate, L-arginine. Since NG-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.
Daghigh
F
F
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Fukuto
J M
JM
Ash
D E
DE
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006706:Homeostasis; D008099:Liver / Q000201:enzymology*; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D013329:Structure-Activity Relationship
D009569:Nitric Oxide; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D001119:Arginase