N-OMEGA-HYDROXY-L-ARGININE, AN INTERMEDIATE IN THE L-ARGININE TO NITRIC-OXIDE PATHWAY, IS A STRONG INHIBITOR OF LIVER AND MACROPHAGE ARGINASE - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemical and Biophysical Research Communications Année : 1994

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

Résumé

N-omega-Hydroxy-L-arginine (L-NOHA) is a potent inhibitor of the hydrolysis of L-arginine (L-Arg) to L-ornithine (L-Orn) catalyzed by purified bovine liver arginase (BLA). It appears as one of the most powerful arginase inhibitors reported so far (Ki = 150 mu M). The other products of NO synthase are either without effect (NO2-, NO3-) or much weaker inhibitors (L-citrulline (L-Cit) and NO) of BLA. Products derived from 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 concentrations up to 2 mM. The configuration of L-NOHA is important as D-NOHA 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 macrophages (IC50 of 150 and 450 mu M, respectively). These remarkable properties 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.N-omega-Hydroxy-L-arginine (L-NOHA) is a potent inhibitor of the hydrolysis of L-arginine (L-Arg) to L-ornithine (L-Orn) catalyzed by purified bovine liver arginase (BLA). It appears as one of the most powerful arginase inhibitors reported so far (Ki = 150 mu M). The other products of NO synthase are either without effect (NO2-, NO3-) or much weaker inhibitors (L-citrulline (L-Cit) and NO) of BLA. Products derived from 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 concentrations up to 2 mM. The configuration of L-NOHA is important as D-NOHA 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 macrophages (IC50 of 150 and 450 mu M, respectively). These remarkable properties 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.
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hal-00315241 , version 1 (27-08-2008)

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  • HAL Id : hal-00315241 , version 1

Citer

Jl Boucher, J. Custot, S. Vadon, M. Delaforge, M. Lepoivre, et al.. N-OMEGA-HYDROXY-L-ARGININE, AN INTERMEDIATE IN THE L-ARGININE TO NITRIC-OXIDE PATHWAY, IS A STRONG INHIBITOR OF LIVER AND MACROPHAGE ARGINASE. Biochemical and Biophysical Research Communications, 1994, 203, pp.1614-1621. ⟨hal-00315241⟩
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