Comparison of substrate and inhibitor specificity of arginase and nitric oxide (NO) synthase for arginine analogues and related compounds in murine and rat macrophages.
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.
Hrabák
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Department of Biochemistry I., Semmelweis University Medical School, Budapest, Hungary.
Bajor
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Temesi
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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
D006709:Homoarginine; C069339:argininamide; D002172:Canavanine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase