PMID- 7945311 OWN - NLM STAT- MEDLINE DCOM- 19941031 LR - 20190612 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 203 IP - 3 DP - 1994 Sep 30 TI - N omega-hydroxyl-L-arginine, an intermediate in the L-arginine to nitric oxide pathway, is a strong inhibitor of liver and macrophage arginase. PG - 1614-21 AB - 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 microM). 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 microM, 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. FAU - Boucher, J L AU - Boucher JL AD - Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Universite Paris V, CNRS URA 400, France. FAU - Custot, J AU - Custot J FAU - Vadon, S AU - Vadon S FAU - Delaforge, M AU - Delaforge M FAU - Lepoivre, M AU - Lepoivre M FAU - Tenu, J P AU - Tenu JP FAU - Yapo, A AU - Yapo A FAU - Mansuy, D AU - Mansuy D LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 31C4KY9ESH (Nitric Oxide) RN - 53054-07-2 (N(omega)-hydroxyarginine) RN - 94ZLA3W45F (Arginine) RN - EC 3.5.3.1 (Arginase) RN - HG18B9YRS7 (Valine) RN - K3Z4F929H6 (Lysine) SB - IM MH - Animals MH - Arginase/*antagonists & inhibitors MH - Arginine/*analogs & derivatives/*metabolism/pharmacology MH - Cattle MH - Kinetics MH - Liver/*enzymology MH - Lysine/pharmacology MH - Macrophages/*enzymology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred DBA MH - Nitric Oxide/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Valine/pharmacology EDAT- 1994/09/30 00:00 MHDA- 1994/09/30 00:01 CRDT- 1994/09/30 00:00 PHST- 1994/09/30 00:00 [pubmed] PHST- 1994/09/30 00:01 [medline] PHST- 1994/09/30 00:00 [entrez] AID - S0006291X84723710 [pii] AID - 10.1006/bbrc.1994.2371 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1994 Sep 30;203(3):1614-21. doi: 10.1006/bbrc.1994.2371.