JBPC  Vol.2 No.3 , August 2011
A predictive kinetic model for inhibitory effect of nitrite on myeloperoxidase catalytic activity towards oxidation of chloride
Myeloperoxidase (MPO) is a neutrophil enzyme that employs hydrogen peroxide (H2O2) to catalyze the oxidation of chloride (Cl) to hypochlorous acid (HOCl). Accepted mechanism is based on rapid reaction of native MPO with H2O2to produce Compound I (MPO-I) which oxidizes Cl through a 2e– transition generating MPO and HOCl. MPO-I also reacts with H2O2 to generate Compound II (MPO-II) which is inactive in 2e oxidation of Cl. Nitrite ( NO2-) inhibits the 2e oxidation of Cl by reaction with MPO-I through 1e transition generating MPO-II and nitrite radical. H2O2 consumption during steady- state catalysis was monitored amperometrically by a carbon fiber based H2O2-biosensor at 25oC. Results demonstrated that in absence of NO2- reactions were monophasic and rapid (complete H2O2 consumption occurs in < 10 s). As concentration of NO2- increases, reactions change to biphasic (rapid step followed by a slow step) and both steps have been inhibited by NO2- . A predictive kinetic model describing the inhibittory effect of NO2- was developed and applied to experimental results The model is based on the assumption that MPO–I cannot be detected during steady-state catalysis. Calculated rate constants are in agreement with those obtained from pre-steady state kinetic methods.

Cite this paper
nullTahboub, Y. and Fares, M. (2011) A predictive kinetic model for inhibitory effect of nitrite on myeloperoxidase catalytic activity towards oxidation of chloride. Journal of Biophysical Chemistry, 2, 202-207. doi: 10.4236/jbpc.2011.23024.
[1]   Mauch, L., Lun, A. and O’Gorman, M.R. (2007) Chronic Granulomatous disease (CGD) and complete myeloperoxidase deficiency both yield strongly reduced dihydrorhodamine 123 test signals but can be easily discerned in routine testing for CGD. Clinical Chemistry, 53, 890- 896. doi:10.1373/clinchem.2006.083444

[2]   Heinecke, J.W., Li, W., Francis, G.A. and Goldstein, J.A. (1993) Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. The Journal of Clinical Investigation, 91, 2866-2872. doi:10.1172/JCI116531

[3]   Malle, E., Buch, T. and Grone, H. J. (2003) Meyelopero- xidases in kidney disease. Kidney International, 64, 1956-1967. doi:10.1046/j.1523-1755.2003.00336.x

[4]   Exner, M., Hermann, M., Hofbauer, R., Hartmann, B., Kapiotis, S. and Gmeiner, B. (2004) Thiocyanate catalyzes myeloperoxidase-initiated lipid oxidation in LDL. Free Radical Biology & Medicine, 37, 146-155. doi:10.1016/j.freeradbiomed.2004.04.039

[5]   Bergt, C., Marsche, G., Panzenboeck, U., Heinecke, J. W., Malle, E. and Sattler, W. (2001) Human neutrophils employ the myeloperoxidase/hydrogen peroxide/chloride system to oxidatively damage apolipoprotein A-I. European Journal of Biochemistry, 268, 3523-3531. doi:10.1046/j.1432-1327.2001.02253.x

[6]   Anderson, M.M., Hazen, S.L., Hsu, F.F. and Heinecke, J.W. (1997) Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxy- propanal, and acrolein. The Journal of Clinical Investigation, 99, 424-432. doi:10.1172/JCI119176

[7]   Nagai, R., Hayashi, C.M., Xia, L., Takkeya, M. and Horiuchi, S. (2002) Class B scavenger receptors CD36 and SR-BI are receptors for hypochlorite-modified low density lipoprotein. The Journal of Biological Chemistry, 277, 48905-48912. doi:10.1074/jbc.M205688200

[8]   Van der Vliet, A., Eiserich, J.P., Halliwell, B. and Cross, C.E. (1997) Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite. The Journal of Biological Chemistry, 272, 7617-7625. doi:10.1074/jbc.272.12.7617

[9]   Eiserich, J.P., Hristova, M., Cross, C.E., Jones, A.D., Freeman, B.A., Halliwell, B. and Van der Vliet, A. (1998) Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature, 391, 393-397. doi:10.1038/34923

[10]   Sampson, J.B., Ye, Y.Z., Rosen, H. and Beckman, J.S. (1998) Myeloperoxidase and horseradish peroxidase catalyze tyrosine nitration in proteins from nitrite and hydrogen peroxide. Archives of Biochemistry and Biophysics, 356, 207-213. doi:10.1006/abbi.1998.0772

[11]   Kettle, A. and Winterbourn, C. (1997) Myeloperoxidase: A key regulator of neutrophil oxidant production. Redox Report, 3, 89-107.

[12]   Hurst, J.K. (1991) Peroxidases in Chemistry and Biology Vol. 1. In: Everse, J., Everse, K. and Grisham, M., Eds., CRC Press, Boca Raton, 37-62.

[13]   Burner, U., Furtmuller, P., Kettle, A., Koppenal, W. and Obinger, C. (2000) Mechanism of reaction of myeloperoxidase with nitrite. The Journal of Biological Chemistry, 275, 20597-2060. doi:10.1074/jbc.M000181200

[14]   Van Dalen, C., Winterbourn, C., Santhilmohan, R. and Kettle, A. (2000) Nitrite as a substrate and inhibitor of myeloperoxidase, The Journal of Biological Chemistry, 275, 11638-11644. doi:10.1074/jbc.275.16.11638

[15]   Kettle, A. and Winterbourn, C. (1994) Assays for the chlorination activity of myeloperoxidase. Methods in Enzymology, 233, 502-512. doi:10.1016/S0076-6879(94)33056-5

[16]   Van Dalen, C., Whiterhouse, M., Winterbourne, C. and Kettle, A. (1997), Thiocyanate and chloride as competing substrates for myeloperoxidase. Biochemical Journal, 327, 487-492.

[17]   Kettle, A. and Winterbourn, C. (2001) A Kinetic analysis of the catalase activity of myeloperoxidase. Biochemistry, 40, 10204-10212. doi:10.1021/bi010940b

[18]   Wang, J. (2005) Carbon nanotube based electrode biosensors: A review, Electroanalysis, 17, 7-14. doi:10.1002/elan.200403113

[19]   World Precision Instruments. www.wpiinc.com

[20]   Tahboub, Y. and Abu-Soud, H. (2010) Steady-state study of inhibitory effect of nitrite on meyeloperoxidase catalytic activity by hydrogen peroxide biosensor. Portugaliae Electrochimica Acta, 28, 27-38. doi:10.4152/pea.201001027

[21]   Rakita, R., Michel, R. and Rosen, H. (1990) Differential inactivation of Escherichia coli membrane dehydrogenases by a myeloperoxidase-mediated antimicrobial system. Biochemistry, 29, 1075-1080. doi:10.1021/bi00456a033

[22]   Wever, R., Plat, H. and Hamers, M. (1981) Human eosinophil peroxidase: A novel isolation procedure, spectral properties and chlorinating activity. Human eosinophil peroxidase: A novel isolation procedure, spectral properties and chlorinating activity. FEBS Letters, 123, 327-333. doi:10.1016/0014-5793(81)80320-1

[23]   Agner, K. (1963) Studies on myeloperoxidase activity. Acta Chemica Scandinavica, 17, S332-S338. doi:10.3891/acta.chem.scand.17s-0332

[24]   Tahboub, Y.R., Galijasevic, S., Diamond M.P. and Abu- Soud, H.M. (2005) Thiocyanate modulates the catalytic activity of mammalian peroxidases. The Journal of Biological Chemistry, 280, 26129-26136. doi:10.1074/jbc.M503027200

[25]   Floris, R., Piersma, S.R., Yang, G., Jones, P. and Wever, R. (1993) Interaction of myeloperoxidase with peroxynitrite. European Journal of Biochemistry, 215, 767-775. doi:10.1111/j.1432-1033.1993.tb18091.x

[26]   Furtmüller, P.G., Burner, U. and Obinger, C. (1998) Reaction of myeloperoxidase compound I with chloride, bromide, iodide, and thiocyanate. Biochemistry, 37, 17923-17930.

[27]   Galijasevic, S., Abdulhamid, I. and Abu-Soud, H.M. (2008) Potential role of tryptophan and chloride in the inhibition of human myeloperoxidase. Biochemistry, 47, 2668-2677. doi:10.1021/bi702016q

[28]   Ashby, M.T., Carlson, A.C. and Scott, M.J. (2004) Redox buffering of hypochlorous acid by thiocyanate in physiologic fluids. Journal of the American Chemical Society, 126, 15976-15977. doi:10.1021/ja0438361

[29]   Proteasa, G., Tahboub, Y., Galijasevic, S., Russel, F. and Abu-Soud, H. (2007) kinetic evidence supports the existence of two halide binding sites that have a distinct impact on the heme microenvironment of myeloperoxidase. Biochemistry, 46, 398-405. doi:10.1021/bi0609725