title: Comparison of substrate and inhibitor specificity of arginase and nitric oxide (NO) synthase for arginine analogues and related compounds in murine and rat macrophages.
abstract: Arginine utilizing enzymes in macrophages showed different specificities for various arginine analogues and derivatives as substrates and inhibitors. Isolated arginase was strongly inhibited by L-canavanine(Can) and L-ornithine(Orn) but only slightly by L-homoarginine(Hom) and L-argininamide(ArgNH2). These effects were not or only weakly observed when released urea was measured in long term cell cultures. On the other hand, both L-canavanine and L-argininamide were substrates for arginase in long-term cultures. The known inhibitors of NO synthase were ineffective. The mechanisms of inhibition were different for L-canavanine and L-ornithine, but clear mechanisms could not be identified). NO synthase was studied only in long term cell cultures without purification. Certain N-guanidino (NG)-substituted arginine derivatives caused a marked inhibition while inhibitors of arginase had only slight or no effect. L-homoarginine was also found to be the substrate of NO synthase. The comparison of these effects of arginine analogues and derivatives made possible a computer-aided approximation for the fitting of active centers of these enzymes to their substrates.
authors.affiliation: Department of Biochemistry I., Semmelweis University Medical School, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Hrabák
authors.forename: T
authors.initials: T
authors.lastname: Bajor
authors.forename: A
authors.initials: A
authors.lastname: Temesi
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002172:Canavanine / Q000494:pharmacology; D002478:Cells, Cultured; D006709:Homoarginine / Q000494:pharmacology; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase; D009952:Ornithine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D006709:Homoarginine; C069339:argininamide; D002172:Canavanine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase