Macrophage Cytotoxicity: Role for L-Arginine Deiminase and Imino Nitrogen Oxidation to Nitrite
| Autor: | Read R. Taintor, John B. Hibbs, Zdenek Vavrin |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Cytotoxicity
Immunologic Cellular immunity Nitrates Multidisciplinary Arginine DNA synthesis Hydrolases Chemistry Effector Macrophages Macrophage Activation Homoarginine Mice chemistry.chemical_compound Biochemistry Biosynthesis Ammonia Animals Citrulline Cytotoxic T cell Nitrite Arginine deiminase Cells Cultured Nitrites |
| Zdroj: | Science. 235:473-476 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.2432665 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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