title: Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite.
abstract: Previous studies have shown that cytotoxic activated macrophages cause inhibition of DNA synthesis, of mitochondrial respiration, and of aconitase activity in tumor target cells. An L-arginine-dependent biochemical pathway synthesizing L-citrulline and nitrite, coupled to an effector mechanism, is now shown to cause this pattern of metabolic inhibition. Murine cytotoxic activated macrophages synthesize L-citrulline and nitrite in the presence of L-arginine but not D-arginine. L-Citrulline and nitrite biosynthesis by cytotoxic activated macrophages is inhibited by NG-monomethyl-L-arginine, which also inhibits this cytotoxic effector mechanism. This activated macrophage cytotoxic effector system is associated with L-arginine deiminase activity, and the imino nitrogen removed from the guanido group of L-arginine by the deiminase reaction subsequently undergoes oxidation to nitrite. L-Homoarginine, an alternative substrate for this deiminase, is converted to L-homocitrulline with concurrent nitrite synthesis and similar biologic effects.
mesh_terms: D000641:Ammonia / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D002956:Citrulline / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006709:Homoarginine / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D006709:Homoarginine; D002956:Citrulline; D000641:Ammonia; D006867:Hydrolases; C019723:arginine deiminase