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...

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Veröffentlicht in:Biochemical and biophysical research communications 1993-12, Vol.197 (2), p.523-528
Hauptverfasser: Robertson, C.A., Green, B.G., Niedzwiecki, L., Harrison, R.K., Grant, S.K.
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Sprache:eng
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Zusammenfassung: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 α-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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1993.2510