Effect of nitric oxide synthase substrate analog inhibitors on rat liver arginase.
Nitric oxide synthase (EC 1.14.23) substrate analog inhibitors NG-monomethyl-L-Arg, NG-nitro-L-Arg, NG-nitro-L-Arg methyl ester, and aminoguanidine were examined as potential inhibitors of rat liver arginase (EC 3.5.3.1). NG-nitro-L-Arg was found to inhibit arginase catalyzed conversion of L-Arg to L-Orn at pH 7.5 with an IC50 = 27.2 +/- 4.3 mM, compared to L-Val and L-Lys with IC50 values of 6.2 +/- 0.4 mM and 31.3 +/- 2.7 mM, respectively. Inhibition was stereospecific for the L-amino acid, not NG-nitro-D-Arg, and required a free alpha-carboxyl group. NG-nitro-L-Arg was not a substrate for rat liver arginase. These results suggest that arginase inhibition should also be evaluated when studying the effects of NOS substrate analog inhibitors in vivo.
Robertson
C A
CA
Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065.
Green
B G
BG
Niedzwiecki
L
L
Harrison
R K
RK
Grant
S K
SK
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase; D019331:NG-Nitroarginine Methyl Ester