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.
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
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F
Daghigh
J M
JM
Fukuto
D E
DE
Ash
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