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.
PO reactions can transduce continuing infusions of hydrogen peroxide and superoxide into bounded dynamics.
-
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.
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
Davies, K.J.: Oxidative stress: the paradox of aerobic life. Biochem. Soc. Sympos. 61, 1–31 (1995)
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)
Chauhan, A., Chauhan, V.: Oxidative stress in autism. Pathophysiology 13, 171–181 (2006)
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)
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)
Chadwick, W., Zhou, Y., Park, S.-S.: Minimal peroxide exposure of neuronal cells induces multifaceted adaptive response. PLoS ONE 5, e14352 (2010)
Starkov, A.A., Fiskum, G., Chinopoulos, C., et al.: Mitochondrial α-ketoglutarate dehydrogenase complex generates reactive oxygen species. J. Neurosci. 24, 7779–7788 (2004)
Murphy, M.P.: How mitochondria produce reactive oxygen species. Biochem. J. 417, 1–13 (2009)
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)
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)
Klebanoff, S.J.: Myeloperoxidase: friend and foe. J. Leucoc. Biol. 77, 598–625 (2005)
Lefkowitz, D.L., Lefkowitz, S.S.: Microglia and myeloperoxidase: a deadly partnership in neurodegenerative disease. J. Free Radic. Biol. Med. 45, 726–731 (2008)
Everse, J., Coates, P.W.: Neurodegeneration and peroxidases. Neurobiol. Aging 30, 1011–1025 (2009)
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)
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)
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)
Olsen, L.F., Bronnikova, T.V., Schaffer, W.M.: Secondary quasiperiodicity in the peroxidase–oxidase reaction. Phys. Chem. Chem. Phys. 4, 1292–1298 (2002)
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)
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)
Kirkor, E.S., Scheeline, A.: Nicotinamide adenine dinucleotide in the horseradish peroxidase–oxidase oscillator. Eur. J. Biochem. 267, 5014–5022 (2000)
Olsen, L.F., Hauser, M.J., Kummer, U.: Mechanism of protection of peroxidase activity by oscillatory dynamics. Eur. J. Biochem. 270, 2796–2804 (2003)
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)
Brasen, J.C., Lunding, A., Olsen, L.F.: Human myeloperoxidase catalyzes an oscillating peroxidase–oxidase reaction. Arch. Biochem. Biophys. 431, 55–62 (2004)
Acker, T., Acker, H.: Cellular oxygen sensing need in CNS function: physiological and pathological implications. J. Exp. Biol. 207, 3171–3188 (2004)
Trap, B.D., Nave, K.A.: Multiple sclerosis: an immune or neurodegenerative disorder? Annu. Rev. Neurosci. 31, 247–269 (2008)
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)
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)
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)
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)
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)
Yamazaki, I., Yokota, K., Nakajima, R.: Oscillatory oxidations of reduced pyridine nucleotide by peroxidase. Biochem. Biophys. Res. Commun. 21, 582–586 (1965)
Nakamura, S.K., Yokota, K., Yamazaki, I.: Sustained oscillations in lactoperoxidase, NADPH and O2 system. Nature 222, 794 (1969)
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)
Fed’kina, V.R., Bronnikova, T.V.: Complex oscillatory regimes in peroxidase–oxidase reaction. Biophysics 40, 36–47 (1995)
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)
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)
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)
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)
Dunford, H.B.: Heme Peroxidases. Wiley, New York (1999)
Metodiewa, D., Dunford, H.B.: The reactions of horseradish peroxidase, lactoperoxidase, and myeloperoxidase with enzymatically generated superoxide. Arch. Biochem. Biophys. 272, 245–253 (1989)
Scheeline, A., Olson, D.L., Williksen, E.P., et al.: The peroxidase–oxidase oscillator and its constituent chemistries. Chem. Rev. 97, 739–756 (1997)
Olsen, L.F., Lunding, A., Kummer, U.: Mechanism of melatonin-induced oscillations in the peroxidase–oxidase reaction. Arch. Biochem. Biophys. 410, 287–295 (2003)
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)
Dunford, H.B.: Peroxidases and Catalases: Biochemistry, Biophysics, Biotechnology and Physiology. Wiley, New York (2010)
Kuznetsov, Y.A.: Elements of Applied Bifurcation Theory. Springer, New York (1995)
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)
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)
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)
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)
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)
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)
Kettle, A.J., Winterbourn, C.C.: A kinetic analysis of the catalase activity of myeloperoxidase. Biochem. 40, 10204–10212 (2001)
Krasowska, A., Konat, G.W.: Vulnerability of brain tissue to inflammatory oxidant, hypochlorous acid. Brain Res. 997, 176–184 (2004)
Yap, Y.W., Whiteman, M., Cheung, N.S.: Chlorinated stress: an under appreciated mediator of neurodegeneration? Cell. Signal. 19, 219–228 (2007)
Trapp, B.D., Stys, P.K.: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 8, 280–291 (2009)
Obrenovitch, T.P.: Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol. Rev. 88, 211–247 (2008)
Ran, R., Xu, K., Lu, A., et al.: Hypoxia preconditioning in the brain. Dev. Neurosci. 27, 87–92 (2005)
Brigati, C., Banelli, B., di Vinci, A., et al.: Inflammation, HIF-1, and the epigenetics that follows. Mediat. Inflamm. 2010, 1–5 (2010)
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)
Nizet, V., Johnson, R.C.: Interdependence of hypoxic and innate immune response. Nat. Rev. Immunol. 9, 609–617 (2009)
Glass, C.K., Saijo, K., Winner, B., et al.: Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918–934 (2010)
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)
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)
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)
Rossignol, D.A.: Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism. Med. Hypotheses 68, 1208–1227 (2007)
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)
Croonenberghs, J., Bosmans, E., Deboutte, D., et al.: Activation of the inflammatory response system in autism. Neuropsychobiology 45, 1–6 (2002)
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)
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
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)
Filipek, P.A., Juranek, J., Nguyen, M.T., et al.: Relative carnitine deficiency in autism. J. Autism Dev. Disord. 34, 615–623 (2004)
Gargus, J.J., Imtiaz, F.: Mitochondrial energy-deficient endophenotype in autism. Am. J. Biochem. Biotechnol. 4, 198–207 (2008)
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)
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)
Shokati, T.: Metabolic trafficking between astrocytes and neurons under hyperammonemia and manganism: nitrogen- and carbon metabolism. Ph.D. Dissert., U. Bremen, Bremen, Germany (2005)
Filipo, V., Buttersworth, R.F.: Neurobiology of ammonia. Prog. Neurobiol. 67, 259–279 (2002)
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)
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)
Hertz, L., Kala, G.: Energy metabolism in brain cells: effects of elevated ammonia concentrations. Metab. Brain Dis. 22, 199–218 (2007)
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)
MacArthur, R.H.: Selection for life tables in periodic environments. Am. Nat. 102, 381–383 (1968)
Author information
Authors and Affiliations
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11071-011-0314-x