Skip to main content

Advertisement

Log in

Peroxidase-ROS interactions

  • Original Paper
  • Published:
Nonlinear Dynamics Aims and scope Submit manuscript

Abstract

Reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion radical, have long been recognized as harmful by-products of oxidative metabolism. Under normal physiologic conditions, hydrogen peroxide and superoxide are detoxified by antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Heme peroxidases (eosinophil peroxidase (EPO), lactoperoxidase (LPO), myeloperoxidase (MPO), etc.) also consume ROS, but unlike scavenging enzymes, are sources of these species as well. In the present paper, we study a well-tested model of the peroxidase–oxidase (PO) reaction based on horseradish peroxidase (HRP) chemistry with regard to the production and consumption of hydrogen peroxide and superoxide. Our principal results are these:

  1. 1.

    PO reactions can transduce continuing infusions of hydrogen peroxide and superoxide into bounded dynamics.

  2. 2.

    Absent exogenous ROS input, and under conditions that retard hydrogen donor autoxidation, PO reactions can manifest low frequency bursting whereby pulses of ROS are produced at clinically significant intervals.

The relevance of these results to the functional significance of fluctuating ROS concentrations in vivo, to neurodevelopmental and neurodegenerative disease and to episodic and progressive symptomatology is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

Abbreviations

α-KGDH:

α-ketoglutarate dehydrogenase

ALS:

Amyotrophic lateral sclerosis

AD:

Alzheimer’s disease

ASD:

Autistic spectrum disorder

CAT:

Catalase

CSTR:

Continuous stirred tank reactor

DCP:

Dichlorophenol

EPO:

Eosinophil peroxidase

ETC:

Electron transport chain

GPx:

Glutathione peroxidase

HA:

Hyperammonemia

HRP:

Horseradish peroxidase

LPO:

Lactoperoxidase

MB:

Methylene blue

MPO:

Myeloperoxidase

MS:

Multiple sclerosis

NADH:

Reduced nicotinamide adenine dinucleotide

NADPH:

Reduced Nicotinamide adenine dinucleotide phosphate

PD:

Parkinson’s disease

PO:

Reaction peroxidase oxidase reaction

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TCA:

Cycle (tricarboxylic acid cycle)

References

  1. Davies, K.J.: Oxidative stress: the paradox of aerobic life. Biochem. Soc. Sympos. 61, 1–31 (1995)

    Google Scholar 

  2. Valco, M., Leibfritz, D., Moncol, J., et al.: Free radicals and antioxidants in normal physiological function and human disease. Int. J. Biochem. Cell Biol. 39, 44–84 (2007)

    Article  Google Scholar 

  3. Chauhan, A., Chauhan, V.: Oxidative stress in autism. Pathophysiology 13, 171–181 (2006)

    Article  MathSciNet  Google Scholar 

  4. Patten, D.A., Germain, M., Kelly, M.A., Slade, R.S.: Reactive oxygen species: stuck in the middle of neurodegeneration. J. Alzheimer’s Dis. 20, S357–367 (2010)

    Google Scholar 

  5. Reynolds, A., Laurie, C., Mosley, R.L., Gendelman, H.E.: Oxidative stress and the pathogenesis of neurodegenerative disorders. Int. Rev. Neurobiol. 82, 297–325 (2007)

    Article  Google Scholar 

  6. Chadwick, W., Zhou, Y., Park, S.-S.: Minimal peroxide exposure of neuronal cells induces multifaceted adaptive response. PLoS ONE 5, e14352 (2010)

    Article  Google Scholar 

  7. Starkov, A.A., Fiskum, G., Chinopoulos, C., et al.: Mitochondrial α-ketoglutarate dehydrogenase complex generates reactive oxygen species. J. Neurosci. 24, 7779–7788 (2004)

    Article  Google Scholar 

  8. Murphy, M.P.: How mitochondria produce reactive oxygen species. Biochem. J. 417, 1–13 (2009)

    Article  Google Scholar 

  9. Stowe, D.F., Camara, A.K.: Mitochondrial reactive species production in excitable cells: modulators of mitochondrial and cell function. Antioxid. Redox Signal. 11, 1373–1414 (2009)

    Article  Google Scholar 

  10. Infanger, D.W., Sharma, R.V., Davisson, R.L.: NADPH oxidases of the brain: distribution, regulation and function. Antioxid. Redox Signal. 8, 1583–1596 (2006)

    Article  Google Scholar 

  11. Klebanoff, S.J.: Myeloperoxidase: friend and foe. J. Leucoc. Biol. 77, 598–625 (2005)

    Article  Google Scholar 

  12. Lefkowitz, D.L., Lefkowitz, S.S.: Microglia and myeloperoxidase: a deadly partnership in neurodegenerative disease. J. Free Radic. Biol. Med. 45, 726–731 (2008)

    Article  Google Scholar 

  13. Everse, J., Coates, P.W.: Neurodegeneration and peroxidases. Neurobiol. Aging 30, 1011–1025 (2009)

    Article  Google Scholar 

  14. Kirkor, E.S., Scheeline, A., Hauser, M.J.B.: Principal component analysis of dynamical features in the peroxidase–oxidase reaction. Anal. Chem. 72, 1381–1388 (2000)

    Article  Google Scholar 

  15. Schaffer, W.M., Bronnikova, T.V., Olsen, L.F.: Nonlinear dynamics of the peroxidase–oxidase reaction: II. Compatibility of an extended mechanistic model with previously reported model-data correspondences. J. Phys. Chem. B 105, 5331–5340 (2001)

    Article  Google Scholar 

  16. Bronnikova, T.V., Schaffer, W.M., Olsen, L.F.: Nonlinear dynamics of the peroxidase–oxidase reaction: I. Bistability and bursting at low enzyme concentrations. J. Phys. Chem. B 105, 310–321 (2001)

    Article  Google Scholar 

  17. Olsen, L.F., Bronnikova, T.V., Schaffer, W.M.: Secondary quasiperiodicity in the peroxidase–oxidase reaction. Phys. Chem. Chem. Phys. 4, 1292–1298 (2002)

    Article  Google Scholar 

  18. Bronnikova, T.V., Fed’kina, V.R., Schaffer, W.M., Olsen, L.F.: Period-doubling bifurcations in a detailed model of the peroxidase–oxidase reaction. J. Phys. Chem. 99, 9309–9312 (1995)

    Article  Google Scholar 

  19. Hauser, M.J.B., Lunding, A., Olsen, L.F.: On the role of methylene blue in the oscillating peroxidase–oxidase reaction. Phys. Chem. Chem. Phys. 2, 1685–1692 (2000)

    Article  Google Scholar 

  20. Kirkor, E.S., Scheeline, A.: Nicotinamide adenine dinucleotide in the horseradish peroxidase–oxidase oscillator. Eur. J. Biochem. 267, 5014–5022 (2000)

    Article  Google Scholar 

  21. Olsen, L.F., Hauser, M.J., Kummer, U.: Mechanism of protection of peroxidase activity by oscillatory dynamics. Eur. J. Biochem. 270, 2796–2804 (2003)

    Article  Google Scholar 

  22. Olsen, L.F., Kummer, U., Kindzelskii, A.L., Petty, H.R.: A model of the oscillatory metabolism of activated neutrophils. Biophys. J. 84, 69–81 (2003)

    Article  Google Scholar 

  23. Brasen, J.C., Lunding, A., Olsen, L.F.: Human myeloperoxidase catalyzes an oscillating peroxidase–oxidase reaction. Arch. Biochem. Biophys. 431, 55–62 (2004)

    Article  Google Scholar 

  24. Acker, T., Acker, H.: Cellular oxygen sensing need in CNS function: physiological and pathological implications. J. Exp. Biol. 207, 3171–3188 (2004)

    Article  Google Scholar 

  25. Trap, B.D., Nave, K.A.: Multiple sclerosis: an immune or neurodegenerative disorder? Annu. Rev. Neurosci. 31, 247–269 (2008)

    Article  Google Scholar 

  26. Guglielmotto, M., Tamagno, E., Danni, O.: Oxidative stress and hypoxia contribute to Alzheimer’s disease pathogenesis: two sides of the same coin. Sci. World J. 9, 781–791 (2009)

    Article  Google Scholar 

  27. Green, P.S., Mendez, A.J., Jacob, J.S., et al.: Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease. J. Neurochem. 90, 724–733 (2004)

    Article  Google Scholar 

  28. Davis, M.J., Hawkins, C.L., Pattison, D.I., Rees, M.D.: Mammalian heme peroxidases: from molecular mechanisms to health implications. Antioxid. Redox Signal. 10, 1199–1235 (2008)

    Article  Google Scholar 

  29. Gray, E., Thomas, T.L., Bertmouni, S., et al.: Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis. Brain Pathol. 18, 86–95 (2008)

    Article  Google Scholar 

  30. Van der Veen, B.S., de Winther, M.P.J., Heeringa, P.: Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease. Antioxid. Redox Signal. 11, 2899–2937 (2009)

    Article  Google Scholar 

  31. Yamazaki, I., Yokota, K., Nakajima, R.: Oscillatory oxidations of reduced pyridine nucleotide by peroxidase. Biochem. Biophys. Res. Commun. 21, 582–586 (1965)

    Article  Google Scholar 

  32. Nakamura, S.K., Yokota, K., Yamazaki, I.: Sustained oscillations in lactoperoxidase, NADPH and O2 system. Nature 222, 794 (1969)

    Article  Google Scholar 

  33. Fed’kina, V.R., Bronnikova, T.V., Ataullakhanov, F.I.: Computer simulation of sustained oscillations in peroxidase–oxidase reaction. Biophys. Chem. 19, 259–264 (1984)

    Article  Google Scholar 

  34. Fed’kina, V.R., Bronnikova, T.V.: Complex oscillatory regimes in peroxidase–oxidase reaction. Biophysics 40, 36–47 (1995)

    Google Scholar 

  35. Aguda, B.D., Frisch, L.L.H., Olsen, L.F.: Experimental evidence of the coexistence of oscillatory and steady states in the peroxidase–oxidase reaction. J. Am. Chem. Soc. 112, 6652–6656 (1990)

    Article  Google Scholar 

  36. Cook, L.S., Larter, R., Shen, P., Geest, T.: Kinetics of the peroxidase–oxidase reaction with immobilized enzyme. J. Phys. Chem. 97, 9060–9063 (1993)

    Article  Google Scholar 

  37. Kindzelskii, A.L., Clark, A.J., Espinoza, J.: Myeloperoxidase accumulates at the neutrophil surface and enhances cell metabolism and oxidant release during pregnancy. Eur. J. Immunol. 36, 1619–1628 (2006)

    Article  Google Scholar 

  38. Olsen, L.F., Lunding, A., Lauritsen, F.R., Allegra, M.: Melatonin activates the peroxidase–oxidase reaction and promotes oscillations. Biochem. Biophys. Res. Commun. 284, 1071–1076 (2001)

    Article  Google Scholar 

  39. Dunford, H.B.: Heme Peroxidases. Wiley, New York (1999)

    Google Scholar 

  40. Metodiewa, D., Dunford, H.B.: The reactions of horseradish peroxidase, lactoperoxidase, and myeloperoxidase with enzymatically generated superoxide. Arch. Biochem. Biophys. 272, 245–253 (1989)

    Article  Google Scholar 

  41. Scheeline, A., Olson, D.L., Williksen, E.P., et al.: The peroxidase–oxidase oscillator and its constituent chemistries. Chem. Rev. 97, 739–756 (1997)

    Article  Google Scholar 

  42. Olsen, L.F., Lunding, A., Kummer, U.: Mechanism of melatonin-induced oscillations in the peroxidase–oxidase reaction. Arch. Biochem. Biophys. 410, 287–295 (2003)

    Article  Google Scholar 

  43. Winterbourn, C.C., Hampton, M.B., Livesey, J.H., Kettle, A.J.: Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome. Implications for microbial killing. J. Biol. Chem. 281, 39860–39869 (2006)

    Article  Google Scholar 

  44. Dunford, H.B.: Peroxidases and Catalases: Biochemistry, Biophysics, Biotechnology and Physiology. Wiley, New York (2010)

    Google Scholar 

  45. Kuznetsov, Y.A.: Elements of Applied Bifurcation Theory. Springer, New York (1995)

    MATH  Google Scholar 

  46. Hiner, A.N.P., Henrandez-Ruiz, J., Williams, G.A., Arnao, M.B., Garcia-Canovas, F., Acosta, M.: Catalase-like oxygen production by horseradish peroxidase must predominantly be an enzyme-catalyzed reaction. Arch. Biochem. Biophys. 392, 295–302 (2001)

    Article  Google Scholar 

  47. Ximenes, V.F., Catalani, L.H., Campa, A.: Oxidation of melatonin and tryptophan by an HRP cycle involving compound III. Biochem. Biophys. Res. Commun. 287(1), 130–134 (2001)

    Article  Google Scholar 

  48. Di Fillipo, M., Sarchielli, P., Picconi, B., Calabresi, P.: Neuroinflammation and synaptic plasticity: theoretical basis for a novel, immune-centered, therapeutic approach to neurological disorders. Trends Pharmacol. Sci. 29, 402–412 (2008)

    Article  Google Scholar 

  49. Di Filippo, M., Chiasserini, D., Tozzi, A., et al.: Mitochondria and the link between neuroinflammation and neurodegeneration. J. Alzheimer’s Dis. 20, S369–S379 (2010)

    Google Scholar 

  50. Cleveland, D.W., Rothstein, J.D.: From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev., Neurosci. 2, 806–819 (2001)

    Article  Google Scholar 

  51. Kettle, A.J., Winterbourn, C.C.: Superoxide modulates the activity of myeloperoxidase and optimizes the production of hypochlorous acid. Biochem. J. 252, 529–536 (1988)

    Google Scholar 

  52. Kettle, A.J., Winterbourn, C.C.: A kinetic analysis of the catalase activity of myeloperoxidase. Biochem. 40, 10204–10212 (2001)

    Article  Google Scholar 

  53. Krasowska, A., Konat, G.W.: Vulnerability of brain tissue to inflammatory oxidant, hypochlorous acid. Brain Res. 997, 176–184 (2004)

    Article  Google Scholar 

  54. Yap, Y.W., Whiteman, M., Cheung, N.S.: Chlorinated stress: an under appreciated mediator of neurodegeneration? Cell. Signal. 19, 219–228 (2007)

    Article  Google Scholar 

  55. Trapp, B.D., Stys, P.K.: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 8, 280–291 (2009)

    Article  Google Scholar 

  56. Obrenovitch, T.P.: Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol. Rev. 88, 211–247 (2008)

    Article  Google Scholar 

  57. Ran, R., Xu, K., Lu, A., et al.: Hypoxia preconditioning in the brain. Dev. Neurosci. 27, 87–92 (2005)

    Article  Google Scholar 

  58. Brigati, C., Banelli, B., di Vinci, A., et al.: Inflammation, HIF-1, and the epigenetics that follows. Mediat. Inflamm. 2010, 1–5 (2010)

    Article  Google Scholar 

  59. Weston, R.M., Jones, M., Jarrott, B., Calloway, J.K.: Inflammatory cell infiltration after endothelin-1-induced cerebral ischemia: histochemiocal and myeloperoxidase correlation with temporal changes in brain injury. J. Cereb. Blood Flow Metab. 27, 100–114 (2007)

    Article  Google Scholar 

  60. Nizet, V., Johnson, R.C.: Interdependence of hypoxic and innate immune response. Nat. Rev. Immunol. 9, 609–617 (2009)

    Article  Google Scholar 

  61. Glass, C.K., Saijo, K., Winner, B., et al.: Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918–934 (2010)

    Article  Google Scholar 

  62. Araghi-Niknam, M., Fatemi, S.H.: Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices of autistic subjects. Cell. Mol. Neurobiol. 23(6), 945–952 (2003)

    Article  Google Scholar 

  63. Zoroglu, S.S., Armatcu, F., Oren, S., et al.: Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur. Arch. Psychiatry Clin. Neurosci. 254, 143–147 (2004)

    Google Scholar 

  64. Yao, Y., Walsh, W.J., McGinnins, W.R., Pratico, D.: Altered vascular phenotype in autism: correlation with oxidative stress. Arch. Neurol. 63, 1161–1164 (2006)

    Article  Google Scholar 

  65. Rossignol, D.A.: Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism. Med. Hypotheses 68, 1208–1227 (2007)

    Article  Google Scholar 

  66. Kim, Y.S., Joh, T.H.: Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease. Exp. Mol. Med. 38, 333–347 (2006)

    Google Scholar 

  67. Croonenberghs, J., Bosmans, E., Deboutte, D., et al.: Activation of the inflammatory response system in autism. Neuropsychobiology 45, 1–6 (2002)

    Article  Google Scholar 

  68. Russo, A.J., Krigsman, A., Jepsen, B., Wakefield, A.: Low serum myeloperoxidase in autistic children with gastrointestinal disease. Clin. Exper. Gastroent. 2, 85–94 (2009)

    Article  Google Scholar 

  69. Rossignol, D.A., Frye, R.E.: Mitochondrial dysfunction in autism spectrum disorder: a systematic review and meta-analysis. Mol. Psychiatry (2011). doi:101038/mp2010.136

    MATH  Google Scholar 

  70. James, S.J., Cutler, P., Melnyk, S., et al.: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am. J. Clin. Nutr. 80, 1611–1617 (2004)

    Google Scholar 

  71. Filipek, P.A., Juranek, J., Nguyen, M.T., et al.: Relative carnitine deficiency in autism. J. Autism Dev. Disord. 34, 615–623 (2004)

    Article  Google Scholar 

  72. Gargus, J.J., Imtiaz, F.: Mitochondrial energy-deficient endophenotype in autism. Am. J. Biochem. Biotechnol. 4, 198–207 (2008)

    Article  Google Scholar 

  73. Nicolai, J., Carr, J.B.: The measurement of blood levels in patients taking valproic acid: looking for problems where they do not exist. Epilepsy Behav. 12, 494–496 (2008)

    Article  Google Scholar 

  74. Rodrigo, R., Cauli, O., Gomez-Pinedo, V., et al.: Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology 139, 675–684 (2010)

    Article  Google Scholar 

  75. Shokati, T.: Metabolic trafficking between astrocytes and neurons under hyperammonemia and manganism: nitrogen- and carbon metabolism. Ph.D. Dissert., U. Bremen, Bremen, Germany (2005)

  76. Filipo, V., Buttersworth, R.F.: Neurobiology of ammonia. Prog. Neurobiol. 67, 259–279 (2002)

    Article  Google Scholar 

  77. Adam-Vizi, V.: Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain. Antioxid. Redox Signal. 7, 1140–1149 (2005)

    Article  Google Scholar 

  78. Tretter, L., Adam-Vizi, V.: Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos. Trans. R. Soc. Lond. B, Biol. Sci. 360, 2335–2345 (2005)

    Article  Google Scholar 

  79. Hertz, L., Kala, G.: Energy metabolism in brain cells: effects of elevated ammonia concentrations. Metab. Brain Dis. 22, 199–218 (2007)

    Article  Google Scholar 

  80. Bejarano, M.P., Terrón, M.P., Paredes, S., et al.: Hydrogen peroxide increases the phagocytic function of human neutrophils by calcium mobilisation. Mol. Cell. Biochem. 296, 77–84 (2007)

    Article  Google Scholar 

  81. MacArthur, R.H.: Selection for life tables in periodic environments. Am. Nat. 102, 381–383 (1968)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W. M. Schaffer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schaffer, W.M., Bronnikova, T.V. Peroxidase-ROS interactions. Nonlinear Dyn 68, 413–430 (2012). https://doi.org/10.1007/s11071-011-0314-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11071-011-0314-x

Keywords

Navigation