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Biological Synthesis of Nitric Oxide from L-Arginine

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Book cover Etiopathogenesis

Part of the book series: Advances in Research on Neurodegeneration ((ARN,volume 2))

Abstract

It has been observed that inorganic nitrogen oxides are enzymatically synthesized from L-arginine (Hibbs et al., 1987a, 1987b; Iyengar et al., 1987; Palmer et al., 1988) (Fig. 1). Nitric oxide (NO) appears to be the biologically active nitrogen oxide released from the various nitric oxide synthase isoforms. In 1988, two laboratories using different methodology demonstrated that NO- is released from cytokine and lipopolysaccharide-treated murine macrophages (Hibbs et al., 1988; Marietta et al., 1988). These experiments unequivocally established NO- as a low molecular weight biosynthetic product of mammalian cells.

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References

  • Adams LB, Hibbs JB Jr, Taintor RR, Krahenbuhl JL (1990): Microbiostatic effect of murine macrophages for Toxoplasma gondii: role of synthesis of inorganic nitrogen oxides from L-arginine. J Immunol 144:2725–2729

    PubMed  CAS  Google Scholar 

  • Adams LB, Franzblau AG, Vavrin Z, Hibbs JB Jr, Krahenbuhl JL (1991): L-Arginine-dependent macrophage effector functions inhibit metabolic activity of Mycobacterium leprae. J Immunol 147:1642–1646

    PubMed  CAS  Google Scholar 

  • Amber IJ, Hibbs JB Jr, Taintor RR, Vavrin Z (1988): Cytokines induce an L-argininedependent effector system in non-macrophage cells. J Leukocyte Biol 44:58–65

    PubMed  CAS  Google Scholar 

  • Amber IJ, Hibbs JB Jr, Parker CJ, Johnson BB, Taintor RR, Vavrin Z (1991): Activated macrophage conditioned medium: Identification of the soluble factors inducing cytotoxicity and the l-arginine dependent effector mechanism. J Leukocyte Biol 49:610–620

    PubMed  CAS  Google Scholar 

  • Beckerman KP, Rogers HW, Corbett JA, Schreiber RD, McDaniel ML, Unanue ER (1993): Release of nitric oxide during the T cell-independent pathway of macrophage activation: Its role in resistance to Listeria monocytogenes. J Immunol 150:888–895

    PubMed  CAS  Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990): Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87: 1620–1624

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS, Snyder SH (1989): Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci USA 86:9030–9033

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS, Synder SH (1990): Isolation of nitric oxide synthetase, a calmodulinrequiring enzyme. Proc Natl Acad Sci USA 87:682–685

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS, Hwang PM, Synder SH (1990): Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347:768–770

    Article  PubMed  CAS  Google Scholar 

  • Brune G, Lapetina EG (1989): J Biol Chem 264:8455–8458

    PubMed  CAS  Google Scholar 

  • Chan J, Xing Y, Magliozzo RS, Bloom BR (1992): Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med 175:1111–1122

    Article  PubMed  CAS  Google Scholar 

  • Curran RD, Billiar TR, Stuehr DJ, Simmons RL (1989): Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of kupffer cells. J Exp Med 170: 1796–1774

    Article  Google Scholar 

  • Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder RH (1991): Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801

    Article  PubMed  CAS  Google Scholar 

  • Denis M (1991): Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cell Immunol 132:150–157

    Article  PubMed  CAS  Google Scholar 

  • Doyle MP, Hoekstra JW (1981): Oxidation of nitrogen oxides by bound dioxygen in hemoproteins. J Inorg Biochem 14:351–358

    Article  PubMed  CAS  Google Scholar 

  • Drapier J-C, Hibbs JB Jr (1986): Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. J Clin Invest 78:790–797

    Article  PubMed  CAS  Google Scholar 

  • Drapier J-C, Hibbs JB Jr (1988): Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effect cells. J Immunol 140:2829–2838

    PubMed  CAS  Google Scholar 

  • Drapier J-C, Pellat C, Yann H (1991): Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages. J Biol Chem 266:10162–10167

    PubMed  CAS  Google Scholar 

  • Fortier AH, Polsinelli T, Green SJ, Nacy CA (1992): Activation of macrophages for destruction of Francisella tularensis: identification of cytokines, effector cells, and effector molecules. Infect Immunol 60:817–825

    CAS  Google Scholar 

  • Gaily JA, Montague PR, Reeke GN, Edelman GM (1990): The NO hypothesis: possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system. Proc Natl Acad Sci USA 87: 3547–3551

    Article  Google Scholar 

  • Garthwaite J, Charles SL, Chess-Williams R (1988): Endothelium-derived relaxing factor on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336:385–388

    Article  PubMed  CAS  Google Scholar 

  • Granger DL, Lehninger AI (1982): Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J Cell Biol 95:527–535

    Article  PubMed  CAS  Google Scholar 

  • Granger DL, Hibbs JB Jr, Perfect JR, Durack DT (1988): Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest 81:1129–1136

    Article  PubMed  CAS  Google Scholar 

  • Granger DL, Hibbs JB Jr, Perfect JR, Durack DT (1990): Metabolic fate of L-arginine in relation to microbiostatic capability of macrophages. J Clin Invest 85:264–273

    Article  PubMed  CAS  Google Scholar 

  • Granger DL, Taintor RR, Cook JL, Hibbs JB Jr (1980): Injury of neoplastic cells by murine macrophages leads to inhibition of mitochondrial respiration. J Clin Invest 65:357–370

    Article  PubMed  CAS  Google Scholar 

  • Green SJ, Meltzer MS, Hibbs JB Jr, Nacy CA (1990): Activated macrophages destroy intracellular. Leishmania major amastigotes by an L-arginine dependent killing mechanism. J Immunol 144:278–283

    PubMed  CAS  Google Scholar 

  • Hibbs JB Jr (1992): Overview of cytotoxic mechanisms and defense of the intracellular environment against microbes. In: The Biology of Nitric Oxide, 2: Enzymology, Biochemistry and Immunology, Moneada S, Marietta MA, Hibbs JB Jr, Higgs EA, eds. London and Chapel Hill: Portland Press

    Google Scholar 

  • Hibbs JB Jr, Remington JS, Stewart CC (1980): Modulation of immunity and host resistance by micro-organisms. Pharmacol Ther 8:37–69

    Article  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z (1984): Iron depletion: possible cause of tumor cell cytotoxicity induced by activated macrophages. Biochem Biophys Res Commun 123:716–723

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z (1987a): Macrophage cytotoxicity: role for L-arginine deiminase activity and imino nitrogen oxidation to nitrite. Science 235:473–476

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Vavrin Z, Taintor RR (1987b): L-Arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol 138:550–565

    PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM (1988): Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94. [Erratum Biochem Biophys Res Commun 1989) 158:624]

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z, Granger DL, Drapier J-C, Amber IJ, Lancaster JR Jr (1990): Synthesis of nitric oxide from a terminal guanidino nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron. In: Nitric Oxide from L-Arginine: A Bioregulatory System. New York: Elsevier

    Google Scholar 

  • Hibbs JB Jr, Westenfelder C, Taintor RR, Vavrin Z, Kablitz G, Baranowski RL, Ward JH, Menlove RL, McMurray MP, Kushner JP, Samlowski W (1992): Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest 89:867–877

    Article  PubMed  Google Scholar 

  • Hope BR, Michael GJ, Knigge KM, Vincent SR (1991): Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814

    Article  PubMed  CAS  Google Scholar 

  • Hutcheson IR, Griffith TM (1991): Release of endothelium-derived relaxing factor is modulated by both frequency and amplitude of pulsatile flow. Am J Physiol 261:H257-H262

    PubMed  CAS  Google Scholar 

  • Ignarro LJ (1989): Heme-dependent activation of soluble guanylate cyclase by nitric oxide: regulation of enzyme activity by porphyrins and metalloporphyrins. Semin Hematol 26:63–76

    PubMed  CAS  Google Scholar 

  • Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987): Endothelium-derived relaxing factor produced and released from artery and vein in nitric oxide. Proc Natl Acad Sci USA 84:9265–9269

    Article  PubMed  CAS  Google Scholar 

  • Iyengar R, Stuehr DR, Marietta MA (1987): Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci USA 84:6369–6373

    Article  PubMed  CAS  Google Scholar 

  • James SI, Glaven J (1989): Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J Immunol 143:4208–4212

    PubMed  CAS  Google Scholar 

  • Kilbourn RG, Belloni P (1990): Endothelial cell production of nitrogen oxides in response to interferon-y in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst 82:772–776

    Article  PubMed  CAS  Google Scholar 

  • Knowles RG, Palacios GM, Palmer RMJ, Moneada S (1989): Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci USA 86:5159–5162

    Article  PubMed  CAS  Google Scholar 

  • Kosaka H, Kazuhiko I, Kiyohiro I, Itiro T (1979): Stoichiometry of the reaction of exyhemoglobin with nitrite. Biochim Biophys Acta 581:184–188

    Article  PubMed  CAS  Google Scholar 

  • Lancaster JR Jr, Hibbs JB Jr (1990): EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc Natl Acad Sci USA 87: 1223–1227

    Article  PubMed  CAS  Google Scholar 

  • Leaf CD, Wishnok JS, Tannenbaum SR (1990): In: Nitric Oxide from L-Arginine: A Bioregulatory System, Moneada S, Higgs EA, eds., pp. 291–299. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division)

    Google Scholar 

  • Lepoivre M, Boudbid H, Petit JF (1989): Antiproliferative activity of y-interferon combined with lipopolysaccharide on murine adenocarcinoma: dependence on an L-arginine metabolism with production of nitrite and citrulline. Can Res 49: 1970–1976

    CAS  Google Scholar 

  • Liew FY, Millott S, Parkinson C, Palmer RMJ, Moneada S (1990): Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol 144:4794–4797

    PubMed  CAS  Google Scholar 

  • Marietta MA, Yoon PS, Iyengar R, Leaf CD, Wishnock JS (1988): Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27:8706–8711

    Article  Google Scholar 

  • Mayer J, Woods M, Vavrin Z, Hibbs JB Jr (1993): Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells. Infect Immunol 61: 491–497

    CAS  Google Scholar 

  • Moncada S, Palmer RM J, Higgs EA (1991): Nitric oxide: physiology, pathology, and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  • Nathan CF (1992): Nitric oxide as a secretory product of mammalian cells: FASEB J 6:3051–3064

    PubMed  CAS  Google Scholar 

  • Nathan CF, Hibbs JB Jr (1991): Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3:65–70

    Article  PubMed  CAS  Google Scholar 

  • Nussler A, Drapier J-C, Renia L, Pied S, Miltgen F, Gentilini M, Maxier D (1991): L-Arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. Eur J Immunol 21:227–230

    Article  PubMed  CAS  Google Scholar 

  • O’dell TJ, Hawkins RD, Kandel ER, Arancio O (1991): Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci USA 88:11285–11289

    Article  PubMed  Google Scholar 

  • Palmer RMJ, Ashton DS, Moneada S (1988): Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666

    Article  PubMed  CAS  Google Scholar 

  • Palmer RMJ, Ferrige AG, Moneada S (1987): Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    Article  PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moneada S (1990): L-Arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 87:5193–5197

    Article  PubMed  CAS  Google Scholar 

  • Schuman EM, Madison DV (1991): A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254:1503–1506

    Article  PubMed  CAS  Google Scholar 

  • Stuehr DJ, Nathan CF (1989): A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169:1543–1555

    Article  PubMed  CAS  Google Scholar 

  • Synder SH (1992): Nitric oxide: first of a new class of neurotransmitters. Science 257:494–496

    Article  Google Scholar 

  • Weiss PA (1967): 1 + 1≠2 (When one plus one does not equal two). In: The Neurosciences: A Study Program, Quarton GE, Melnechuck T, eds. New York: Rockefeller University Press

    Google Scholar 

  • Wennmalm A, Benthin G, Petersson AS (1992): Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin. Br J Pharmacol 106:507–508

    PubMed  CAS  Google Scholar 

  • Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra J, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS, Keefer LK (1992): DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254:1001–1003

    Article  Google Scholar 

  • Zhang J, Synder SH (1992): Nitric oxide stimulates auto-ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase. Proc Natl Acad Sci USA 89:9382–9385

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. John B. Hibbs Jr.
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Editors and Affiliations

  1. Department of Neurology, Juntendo University School of Medicine, Hongo, Bunkyo, Tokyo 113, Japan

    Yoshikuni Mizuno

  2. Neurodegenerative Disorders Center, The University of British Columbia, Purdy Pavillion, Vancouver, B.C., Canada, V6T 1W5

    Donald B. Calne (Director) (Director)

  3. Health Sciences Center, The Vancouver Hospital, 2211 Wesbrook Mall, Vancouver, B.C., Canada, V6T 1W5

    Donald B. Calne (Director) (Director)

  4. Clinical Research, Special Research Projects, Schering AG Berlin, Müllerstraße 170-178, D-1000, Berlin 65, Germany

    R. Horowski

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© 1994 Birkhäuser Boston

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Hibbs, J.B. (1994). Biological Synthesis of Nitric Oxide from L-Arginine. In: Mizuno, Y., Calne, D.B., Horowski, R. (eds) Etiopathogenesis. Advances in Research on Neurodegeneration, vol 2. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4684-9203-3_8

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  • DOI: https://doi.org/10.1007/978-1-4684-9203-3_8

  • Publisher Name: Birkhäuser, Boston, MA

  • Print ISBN: 978-1-4684-9205-7

  • Online ISBN: 978-1-4684-9203-3

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