Publication Date:
1987-01-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hibbs, J B Jr -- Taintor, R R -- Vavrin, Z -- New York, N.Y. -- Science. 1987 Jan 23;235(4787):473-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2432665" target="_blank"〉PubMed〈/a〉
Keywords:
Ammonia/biosynthesis
;
Animals
;
Cells, Cultured
;
Citrulline/biosynthesis
;
Cytotoxicity, Immunologic
;
Homoarginine/metabolism
;
Hydrolases/metabolism
;
*Macrophage Activation
;
Macrophages/*physiology
;
Mice
;
Nitrates/metabolism
;
Nitrites/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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