From Atmospheric Nitrogen to Bioactive Nitrogen Oxides

  • Mark Gilchrist
  • Nigel Benjamin
Part of the Nutrition and Health book series (NH)


The enrichment of the biosphere with reactive nitrogen from anthropogenic origin, in combination with increased consumption of vegetables and (preserved) animal products, has led to increased intake by humans of nitrite and nitrate. Nitrate and nitrate-forming salts are among the key components of fertilizers and the increased dependency of farming practices on such fertilizers over several decades has led to increasing levels of human exposure. Elemental nitrogen is fixed by several mechanisms including lightning fixation and by symbiotic organisms in the soil. Plants and vegetables use these nitrogen intermediates as an energy source necessary for growth. Understanding nitrogen fixation in the environment by micro-organisms will help in our understanding of the role of nitrite, nitrite, and nitric oxide in humans. The scope of this chapter is to review the mechanisms of nitrogen fixation and how this relates to human nitrogen cycle and human health and disease.


Nitrogen fixation Bacteria Symbiosis Nitrate reductase Fertilizers Denitrification 


  1. 1.
    Feelisch M, Martin JF. The early role of nitric oxide in evolution. Trends Ecol Evol. 1995;10(12):496–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Addiscott T. Nitrate, agriculture and the environment. Oxford: CABI; 2005.Google Scholar
  3. 3.
    Kiernan VG. Foreign interests in the War of the Pacific. Hisp Am Hist Rev. 1955;35(1):14–36.CrossRefGoogle Scholar
  4. 4.
    Harutyunyan EH et al. The structure of deoxy- and oxy-leghaemoglobin from Lupin. J Mol Biol. 1995;251(1):104–15.CrossRefPubMedGoogle Scholar
  5. 5.
    Smil V. Enriching the earth: Fritz Haber, Carl Bosch, and the transformation of world food production. Cambridge: MIT; 2004.Google Scholar
  6. 6.
    Schlesinger WH. On the fate of anthropogenic nitrogen. Proc Natl Acad Sci. 2009;106(1):203–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Vitousek PM, Aber JD, Howarth RW, Likens GE, Matson PA, Schindler DW, et al. Human alteration of the global nitrogen cycle: sources and consequences. Ecol Appl. 1997;7(3):737–50.Google Scholar
  8. 8.
    Schumann U, Huntrieser H. The global lightning-induced nitrogen oxides source. Atmos Chem Phys. 2007;7(14):3823–907.CrossRefGoogle Scholar
  9. 9.
    Barth KR, Isabella VM, Clark VL. Biochemical and genomic analysis of the denitrification pathway within the genus Neisseria. Microbiology. 2009;155(12):4093–103.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Moir JW, Wood NJ. Nitrate and nitrite transport in bacteria. Cell Mol Life Sci. 2001;58(2):215–24.CrossRefPubMedGoogle Scholar
  11. 11.
    Cutruzzolà F. Bacterial nitric oxide synthesis. Biochim Biophys Acta. 1999;1411(2–3):231–49.CrossRefPubMedGoogle Scholar
  12. 12.
    Hendriks J, Oubrie A, Castresana J, Urbani A, Gemeinhardt S, Saraste M. Nitric oxide reductases in bacteria. Biochim Biophys Acta. 2000;1459(23):266–73.CrossRefPubMedGoogle Scholar
  13. 13.
    Zumft W. Cell biology and molecular basis of denitrification. Microbiol Mol Biol Rev. 1997;61(4):533–616.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Schreiber F, Stief P, Gieseke A, Heisterkamp I, Verstraete W, de Beer D, et al. Denitrification in human dental plaque. BMC Biol. 2010;8(1):24.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Moreno-Vivián C, Ferguson SJ. Definition and distinction between assimilatory, dissimilatory and respiratory pathways. Mol Microbiol. 1998;29(2):664–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Berks BC, Ferguson SJ, Moir JWB, Richardson DJ. Enzymes and associated electron transport systems that catalyse the respiratory reduction of nitrogen oxides and oxyanions. Biochim Biophys Acta. 1995;1232(3):97–173.CrossRefPubMedGoogle Scholar
  17. 17.
    Parham NJ, Gibson GR. Microbes involved in dissimilatory nitrate reduction in the human large intestine. FEMS Microbiol Ecol. 2000;31(1):21–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Bothe H, Ferguson SJ, Newton WE. Biology of the nitrogen cycle. 1st ed. Amsterdam: Elsevier; 2007.Google Scholar
  19. 19.
    Jetten MSM, Strous M, Pas-Schoonen KT, Schalk J, Dongen UGJM, Graaf AA, et al. The anaerobic oxidation of ammonium. FEMS Microbiol Rev. 1998;22(5):421–37.CrossRefPubMedGoogle Scholar
  20. 20.
    Strous M, Heijnen JJ, Kuenen JG, Jetten MSM. The sequencing batch reactor as a powerful tool for the study of slowly growing anaerobic ammonium-oxidizing microorganisms. Appl Microbiol Biotechnol. 1998;50(5):589–96.CrossRefGoogle Scholar
  21. 21.
    Isaka K, Date Y, Sumino T, Yoshie S, Tsuneda S. Growth characteristic of anaerobic ammonium-oxidizing bacteria in an anaerobic biological filtrated reactor. Appl Microbiol Biotechnol. 2006;70(1):47–52.CrossRefPubMedGoogle Scholar
  22. 22.
    Fulgoni III VL. Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003–2004. Am J Clin Nutr. 2008;87(5):1554S–7.PubMedGoogle Scholar
  23. 23.
    Forte P, Dykhuizen RS, Milne E, McKenzie A, Smith CC, Benjamin N. Nitric oxide synthesis in patients with infective gastroenteritis. Gut. 1999;45(3):355–61.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Huntington GB, Archibeque SL. Practical aspects of urea and ammonia metabolism in ruminants. J Anim Sci. 2000;77(E-Suppl):1–11.CrossRefGoogle Scholar
  25. 25.
    Doel JJ, Benjamin N, Hector MP, Rogers M, Allaker RP. Evaluation of bacterial nitrate reduction in the human oral cavity. Eur J Oral Sci. 2005;113(1):14–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Duncan C, Dougall H, Johnston P, Green S, Brogan R, Leifert C, et al. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate [see comment]. Nat Med. 1995;1(6):546–51.CrossRefPubMedGoogle Scholar
  27. 27.
    Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith L, Golden M, et al. Stomach NO synthesis [see comment]. Nature. 1994;368(6471):502.CrossRefPubMedGoogle Scholar
  28. 28.
    Wallace JL, Miller MJ. Nitric oxide in mucosal defense: a little goes a long way. Gastroenterology. 2000;119(2):512–20.CrossRefPubMedGoogle Scholar
  29. 29.
    Dykhuizen RS, Frazer R, Duncan C, Smith CC, Golden M, Benjamin N, et al. Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense. Antimicrob Agents Chemother. 1996;40(6):1422–5.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Weller R, Pattullo S, Smith L, Golden M, Ormerod A, Benjamin N. Nitric oxide is generated on the skin surface by reduction of sweat nitrate. J Invest Dermatol. 1996;107(3):327–31.CrossRefPubMedGoogle Scholar
  31. 31.
    Weller R, Price RJ, Ormerod AD, Benjamin N, Leifert C. Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens. J Appl Microbiol. 2001;90(4):648–52.CrossRefPubMedGoogle Scholar
  32. 32.
    Benjamin N, Pattullo S, Weller R, Smith L, Ormerod A. Wound licking and nitric oxide [see comment]. Lancet. 1997;349(9067):1776.CrossRefPubMedGoogle Scholar
  33. 33.
    Hord NG, Ghannam JS, Garg HK, Berens PD, Bryan NS. Nitrate and nitrite content of human, formula, bovine and soy milks: implications for dietary nitrite and nitrate recommendations. Breastfeed Med. 2011;6(6):393–9.Google Scholar
  34. 34.
    Wagner DA, Schultz DS, Deen WM, Young VR, Tannenbaum SR. Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid. Cancer Res. 1983;43(4):1921–5.PubMedGoogle Scholar
  35. 35.
    Godfrey M, Majid DS. Renal handling of circulating nitrates in anesthetized dogs. Am J Physiol. 1998;275(1 Pt 2):F68–73.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Peninsula Medical SchoolExeterUK

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