Effect of nitric oxide synthase substrate analog inhibitors on rat liver arginase

Biochem Biophys Res Commun. 1993 Dec 15;197(2):523-8. doi: 10.1006/bbrc.1993.2510.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / metabolism*
  • Animals
  • Arginase / antagonists & inhibitors
  • Arginase / metabolism*
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Kinetics
  • Liver / enzymology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase
  • Nitroarginine
  • Rats
  • omega-N-Methylarginine

Substances

  • Nitroarginine
  • omega-N-Methylarginine
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Arginase
  • NG-Nitroarginine Methyl Ester