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Science 23 January 1987:
Vol. 235. no. 4787, pp. 473 - 476
DOI: 10.1126/science.2432665
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Articles

Science, Vol 235, Issue 4787, 473-476
Copyright © 1987 by American Association for the Advancement of Science

articles

Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite

JB Hibbs Jr, RR Taintor, and Z Vavrin

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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Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase.
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Arch Surg 128, 396-401
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Biochemistry of nitric oxide and its redox-activated forms.
J. Stamler, D. Singel, and J Loscalzo (1992)
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Effect of Endogenous Nitric Oxide on Mitochondrial Respiration of Rat Hepatocytes In Vitro and In Vivo.
J. Stadler, R. D. Curran, J. B. Ochoa, B. G. Harbrecht, R. A. Hoffman, R. L. Simmons, and T. R. Billiar (1991)
Arch Surg 126, 186-191
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Distinction between Nitrosating Mechanisms within Human Cells and Aqueous Solution.
M. G. Espey, K. M. Miranda, D. D. Thomas, and D. A. Wink (2001)
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