title: Computer-aided comparison of the inhibition of arginase and nitric oxide synthase in macrophages by amino acids not related to arginine.
abstract: Macrophages contain arginase and an inducible nitric oxide (NO) synthase that use the same substrate, L-arginine, to produce nitric oxide and urea, respectively. Arginase was inhibited by various amino acids not related to L-arginine. These compounds were bound to the substrate binding site of the enzyme as supported by kinetic studies. Five binding sites were defined in this area by computer-aided analysis, and three complementary sites in a compound were sufficient to give an inhibitory character. NO synthase could not be inhibited by these compounds, but certain derivatives (e.g., putrescine or L-valinol) caused a marked and probably allosteric inhibition. The possible biological importance of these inhibitions in the tumoricid function of macrophages is discussed.
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: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors*; D001120:Arginine / Q000378:metabolism; D002478:Cells, Cultured; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase; D011700:Putrescine