Cited by 1,527Immune cells in cancerAmino Acid Enzymes and MetabolismCancer Research and Treatments

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

Hibbs, John B., Taintor, Read R., Vavrin, Zdenek·1987·Science

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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Crossref · 10.1126/science.2432665

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Authors
Hibbs, J. B., Taintor, R. R., & Vavrin, Z.
Affiliations
University of Utah (US)
Venue
Science
Published
1987-01-23
Volume
235
Issue
4787
Pages
473-476
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2057025197
Cited by
1,527
References
1
Citations by year
2026: 6 · 2025: 11 · 2024: 6 · 2023: 4 · 2022: 15 · 2021: 24 · 2020: 23 · 2019: 22 · 2018: 14 · 2017: 24 · 2016: 28 · 2015: 21 · 2014: 30 · 2013: 24 · 2012: 30
FWCI
17.60
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
Keywords
macrophage cytotoxicity, citrulline, L-arginine, L-NMMA, L-homoarginine, DNA synthesis inhibition, mitochondrial respiration inhibition, aconitase inhibition, tumor target cells, macrophage activation
MeSH terms
Ammonia, Animals, Cells, Cultured, Citrulline, Cytotoxicity, Immunologic, Homoarginine, Hydrolases, Macrophage Activation, Macrophages, Nitrates, Nitrites, Mice

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