EFFECT OF NITRIC-OXIDE SYNTHASE SUBSTRATE-ANALOG INHIBITORS ON RAT-LIVER ARGINASE

Nitric oxide synthase (EC 1.14.23) substrate analog inhibitors N(G)- monomethyl-L-Arg, N(G)-nitro-L-Arg, N(G)-nitro-L-Arg methyl ester, and aminoguanidine were examined as potential inhibitors of rat liver arginase (EC 3.5.3.1). N(G)-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 N(G)-nitro-D-Arg, and required a free α-carboxyl group. N(G)-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. © 1993 Academic Press, Inc.