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.
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Authors | J B Hibbs Jr, R R Taintor, Z Vavrin |
Journal | Science (New York, N.Y.)
(Science)
Vol. 235
Issue 4787
Pg. 473-6
(Jan 23 1987)
ISSN: 0036-8075 [Print] United States |
PMID | 2432665
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Nitrates
- Nitrites
- Homoarginine
- Citrulline
- Ammonia
- Hydrolases
- arginine deiminase
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Topics |
- Ammonia
(biosynthesis)
- Animals
- Cells, Cultured
- Citrulline
(biosynthesis)
- Cytotoxicity, Immunologic
- Homoarginine
(metabolism)
- Hydrolases
(metabolism)
- Macrophage Activation
- Macrophages
(physiology)
- Mice
- Nitrates
(metabolism)
- Nitrites
(metabolism)
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