Consumption of L-arginine mediated by Entamoeba histolytica L-arginase (EhArg) inhibits amoebicidal activity and nitric oxide production by activated macrophages.
In this study we discuss the cloning and expression of Entamoeba histolytica arginase (EhArg), an enzyme that catalyses the hydrolysis of L-arginine to L-ornithine and urea. L-norvaline, a competitive inhibitor of E. histolytica L-arginase, inhibits the growth of the parasite, which suggests that the catabolism of L-arginine mediated by EhArg is essential. Nitric oxide (NO) is an antimicrobial agent that inhibits some key enzymes in the metabolism of Entamoeba histolytica. NO is synthesized by activated macrophages from L-arginine, the substrate of NO synthase (NOS-II). We show that E. histolytica inhibits NO mediated amoebicidal activity of activated macrophages by consuming L-arginine present in the medium.
Elnekave
Keren
K
Department of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Siman-Tov
Rama
R
Ankri
Serge
S
D000595:Amino Acid Sequence; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017077:Culture Media, Conditioned; D018076:DNA, Complementary / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D016054:DNA, Protozoan; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D009569:Nitric Oxide; D001120:Arginine; C005313:norvaline; D001119:Arginase; D014633:Valine