N-OMEGA-HYDROXY-L-ARGININE, AN INTERMEDIATE IN THE L-ARGININE TO NITRIC-OXIDE PATHWAY, IS A STRONG INHIBITOR OF LIVER AND MACROPHAGE ARGINASE

N-omega-Hydroxy-L-arginine (L-NOHA) is a potent inhibitor of the hydro lysis of L-arginine (L-Arg) to L-ornithine (L-Orn) catalyzed by purifi ed bovine liver arginase (BLA). It appears as one of the most powerful arginase inhibitors reported so far (Ki = 150 mu M). The other produc ts of NO synthase are either without effect (NO2-, NO3-) or much weake r inhibitors (L-citrulline (L-Cit) and NO) of BLA. Products derived fr om a possible hydrolysis of L-Arg (L-Orn and urea) or of L-NOHA (L-Cit , hydroxyurea and hydroxylamine) are also inactive toward BLA at conce ntrations up to 2 mM. The configuration of L-NOHA is important as D-NO HA is much less active, and its free -COOH and alpha-NH2 functions are required for recognition of BLA. L-NOHA is also a potent inhibitor of the arginase activity of rat liver homogenates and of murine macropha ges (IC50 of 150 and 450 mu M, respectively). These remarkable propert ies of L-NOHA could play a role in the modulation of the biosynthesis of the biological mediator NO by increasing local L-Arg concentrations . (C) 1994 Academic Press, Inc.