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The Mechanism of Lipoxygenases

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Active Oxygen in Biochemistry

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Abstract

Lipoxygenases catalyze the biosynthesis of fatty acid hydroperoxides from polyunsaturated fatty acids and fatty acid esters. In mammals the fatty acid hydroperoxides are substrates for the pathways that lead to leukotrienes and lipoxins, potent messengers that are involved in the inflammatory response (Samuelsson et al., 1987; Wasserman et al., 1991). Consequently, lipoxygenase inhibitors have been a major goal of the pharmaceutical industry as potential drugs against, e.g., arthritis and asthma (Batt, 1992; McMillan and Walker, 1992). The fatty acid hydroperoxides themselves may play a role in a variety of phenomena, including cell maturation and the development of atherosclerosis (see Chapter 10) (Schewe and Kühn, 1991). In plants the role of lipoxygenase is less well understood; here the fatty acid hydroperoxide is a substrate for pathways that lead to production of species such as jasmonic and traumatic acids that appear to be involved in events as diverse as development and growth regulation, wound response, and pest resistance (Gardner, 1991; Hildebrand and Grayburn, 1991; Siedow, 1991). The most familiar role of these fatty acid hydroperoxides, however, is as substrates for the production of cis-3-hexenol and trans-2-hexenal, the species responsible for the odor of new-mown grass.

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References

  • Arasasingham, R. D., Balch, A. L., Cornman, C. R., and Latos, G. L. (1989) Dioxygen Insertion into Iron(III)-Carbon Bonds. Nmr Studies of the Formation and Reactivity of Alkylperoxo Complexes of Iron(III) Porphyrins. J. Am. Chem. Soc., 111, 4357–4363.

    Google Scholar 

  • Arasasingham, R. D., Balch, A. L., Har, R. L., and Latos, G. L. (1990) Reactions of Aryliron(III) Porphyrins with Dioxygen. Formation of Aryloxyiron(III) and Aryliron(IV) Complexes. J. Am. Chem. Soc., 112, 7566–7571.

    Google Scholar 

  • Baldwin, J. E., and Bradley, M. (1990) Isopenicillin N Synthase: Mechanistic Studies. Chem. Rev., 90, 1079–1088.

    Google Scholar 

  • Batt, D. G. (1992) 5-Lipoxygenase Inhibitors and Their Anti-inflammatory Activities. Prog. Med. Chem., 29, 1–63

    Google Scholar 

  • Boyington, J. C., Gaffney, B. J., and Amzel, L. M. (1993) The Three-dimensional Structure of an Arachidonic Acid 15-Lipoxygenase. Science (Washington, D. C.), 260, 1482–1486.

    Google Scholar 

  • Brash, A. R., Ingram, C. D., and Maas, R. L. (1986) A Secondary Isotope Effect in the Lipoxygenase Reaction. Biochim. Biophys. Acta, 875, 256–261.

    Google Scholar 

  • Castellino, A. J., and Bruice, T. C. (1988a) Intermediates in the Epoxidation of Alkenes by Cytochrome P-450 Models. 2. Use of the trans-2, trans-3-Diphenylcyclopropyl Substituent in a Search of Radical Intermediates. J. Am. Chem. Soc., 110, 7512–7519.

    Google Scholar 

  • Castellino, A. J., and Bruice, T. C. (1988b) Radical Intermediates in the Epoxidation of Alkenes by Cytochrome P-450 Model Systems. The Design of a Hypersensitive Radical Probe. J. Am. Chem. Soc., 110, 1313–1315.

    Google Scholar 

  • Chamulitrat, W., Hughes, M. F., Eling, T. E., and Mason, R. P. (1991) Superoxide and Peroxyl Radical Generation from the Reduction of Polyunsaturated Fatty Acid Hydroperoxides by Soybean Lipoxygenase. Arch. Biochem. Biophys., 290, 153–159.

    Google Scholar 

  • Chamulitrat, W., and Mason, R. P. (1989) Lipid Peroxyl Radical Intermediates in the Peroxidation of Polyunsaturated Fatty Acids by Lipoxygenase. Direct Electron Spin Resonance Investigations. J. Biol. Chem., 264, 20968–20973.

    Google Scholar 

  • Chamulitrat, W., and Mason, R. P. (1990) Alkyl Free Radicals from the Beta-scission of Fatty Acid Alkoxyl Radicals as Detected by Spin Trapping in a Lipoxygenase System. Arch. Biochem. Biophys., 282, 65–69.

    Google Scholar 

  • Cheesbrough, T. M., and Axelrod, B. (1983) Determination of the Spin State in Native and Activated Soybean Lipoxygenase 1 by Paramagnetic Susceptibility. Biochemistry, 22, 3837–3840.

    Google Scholar 

  • Clapp, C. H., Banerjee, A., and Rotenberg, S. A. (1985) Inhibition of Soybean Lipoxygenase 1 by N-alkylhydroxylamines. Biochemistry, 24, 1826–1830.

    Google Scholar 

  • Corey, E. J. (1987) Enzymic Lipoxygenation of Arachidonic Acid: Mechanism, Inhibition, and Role in Eicosanoid Biosynthesis. Pure Appl. Chem., 59, 269–278.

    Google Scholar 

  • Corey, E. J., D’Alarcao, M., and Matsuda, S. P. T. (1986) A New Irreversible Inhibitor of Soybean Lipoxygenase: Relevance to Mechanism. Tetrahedron Lett., 27, 3585–3588.

    Google Scholar 

  • Corey, E. J., Lansbury, P. T. J., Cashman, J. R., and Kantner, S. S. (1984) Mechanism of the Irreversible Deactivation of Arachidonate 5-Lipoxygenase by 5,6-Dehydroarachidonate. J. Am. Chem. Soc., 106, 1501–1503.

    Google Scholar 

  • Corey, E. J., and Mehrotra, M. M. (1983) Stereochemistry of the Lipoxygenase-catalyzed Allylic Hydroperoxide → Oxiranylcarbinol Rearrangement. Tetrahedron Lett., 24, 4921–4922.

    Google Scholar 

  • Corey, E. J., and Nagata, R. (1987) Evidence in Favor of an Organoironmediated Pathway for Lipoxygenation of Fatty Acids by Soybean Lipoxygenase. J. Am. Chem. Soc., 109, 8107–8108.

    Google Scholar 

  • Corey, E. J., Nicolaou, K. C., Shibasaki, M., Machida, Y., and Shiner, C. S. (1975) Superoxide Ion as a Synthetically Useful Oxygen Nucleophile. Tetrahedron Lett., 16, 3183–3186.

    Google Scholar 

  • Corey, E. J., and Walker, J. C. (1987) Organoiron-mediated Oxygenation of Allylic Organotin Compounds. A Possible Chemical Model for Enzymatic Lipoxygenation. J. Am. Chem. Soc., 109, 8108–8109.

    Google Scholar 

  • De Groot, J. J. M. C., Garssen, G. J., Veldink, G. A., Vliegenthart, J. F. G., and Boldingh, J. (1975) On the Interaction of Soybean Lipoxygenase-1 and 13-L-Hydroperoxylinoleic Acid, Involving Yellow- and Purplecoloured Enzyme Species. Febs Lett., 56, 50–54.

    Google Scholar 

  • De Groot, J. J. M. C., Garssen, G. J., Vliegenthart, J. F. G., and Boldingh, J. (1973) The Detection of Linoleic Acid Radicals in the Anaerobic Reaction of Lipoxygenase. Biochim. Biophys. Acta, 326, 279–284.

    Google Scholar 

  • De Groot, J. J. M. C., Veldink, G. A., Vliegenthart, J. F. G., Boldingh, J., Wever, R., and Van Gelder, B. F. (1975) Demonstration by EPR Spectroscopy of the Functional Role of Iron in Soybean Lipoxygenase-1. Biochim. Biophys. Acta, 377, 71–79.

    Google Scholar 

  • Dewar, M. J. S., and Thiel, W. (1977) MINDO/3 Study of the Addition of Singlet Oxygen (1Δg) to 1,3-Butadiene. J. Am. Chem. Soc., 99, 2338–2339.

    Google Scholar 

  • Dixon, R. A. F., Jones, R. E., Diehl, R. E., Bennett, C. D., Kargman, S., and Rouzer, C. A. (1988) Cloning of the cDNA for Human 5-Lipoxygenase. Proc. Natl. Acad. Sci. U.S.A., 85, 416–420.

    Google Scholar 

  • Dowd, P. (1990) On the Mechanism of Action of Vitamin B12, in Selective Hydrocarbon Activation (J. A. Davies, P. L. Watson, A. Greenberg, and J. F. Liebman, Eds.), VCH, New York, pp. 265–303.

    Google Scholar 

  • Dunham, W. R., Carroll, R. T., Thompson, J. F., Sands, R. H., and Funk, M. O., Jr. (1990) The Initial Characterization of the Iron Environment in Lipoxygenase by Mössbauer Spectroscopy. Eur. J. Biochem., 190, 611–617.

    Google Scholar 

  • Dussault, M. H., and Hayden, M. R. (1992) Auxiliary-directed Dioxygenation: Stereoselective Synthesis of a Diene Hydroperoxide. Tetrahedron Lett., 33, 443–446.

    Google Scholar 

  • Dussault, P. (1995) Reactions of Hydroperoxides and Peroxides, in Active Oxygen in Chemistry (C. S. Foote, J. S. Valentine, A. Greenberg, and J. F. Liebman, Eds.), Chapman & Hall, New York, pp. 141–203.

    Google Scholar 

  • Egmond, M. R., Fasella, P. M., Veldink, G. A., Vliegenthart, J. F. G., and Boldingh, J. (1977) On the Mechanism of Action of Soybean Lipoxygenase. A Stopped-flow Kinetic study of the Formation and Conversion of Yellow and Purple Enzyme Species. Eur. J. Biochem., 76, 469–479.

    Google Scholar 

  • Egmond, M. R., Veldink, G. A., Vliegenthart, J. F. G., and Boldingh, J. (1973) C-11 H-abstraction from Linoleic Acid, the Rate-limiting Step in Lipoxygenase Catalysis. Biochem. Biophys. Res. Commun., 54, 1178–1184.

    Google Scholar 

  • Egmond, M. R., Vliegenthart, J. F. C., and Boldingh, J. (1972) Stereospecificity of the Hydrogen Abstraction at Carbon Atom n-8 in the Oxygenation of Linoleic Acid by Lipoxygenases from Corn Germs and Soya Beans. Biochem. Biophys. Res. Commun., 48, 1055–1060.

    Google Scholar 

  • Feiters, M. C., Aasa, R., Malmström, B. G., Veldink, G. A., and Vliegenthart, J. F. G. (1986) Spectroscopic Studies on the Interactions Between Lipoxygenase-2 and Its Product Hydroperoxides. Biochim. Biophys. Acta, 873, 182–189.

    Google Scholar 

  • Feiters, M. C., Boelens, H., Veldink, G. A., Vliegenthart, J. F. G., Navaratnam, S., Allen, J. C., Nolting, H.-F., and Hermes, C. (1990) X-ray Absorption Spectroscopic Studies on Iron in Soybean Lipoxygenase: A Model for Mammalian Lipoxygenases. Rec. Trav. Chim. Pays-Bas, 109, 133–146.

    Google Scholar 

  • Foote, C. S., and Clennan, E. (1995) Reactions of Singlet Dioxygen, in Active Oxygen in Chemistry (C. S. Foote, J. S. Valentine, J. F. Liebman, and A. Greenberg, Eds.), Chapman & Hall, New York, pp. 105–140.

    Google Scholar 

  • Frey, P. A., and Reed, G. H. (1993) Lysine 2,3-aminomutase and the Mechanism of the Interconversion of Lysine and β-lysine. Adv. Enzymol., 66, 1–39.

    Google Scholar 

  • Funk, C. D., Furci, L., and Fitzgerald, G. A. (1990) Molecular Cloning, Primary Structure, and Expression of the Human Platelet/Erythroleukemia Cell 12-Lipoxygenase. Proc. Na tl. Acad. Sci. U.S.A., 87, 5638–5642.

    Google Scholar 

  • Funk, M. O. Jr., Andre, J. C., and Otsuki, T. (1987) Oxygenation of trans Polyunsaturated Fatty Acids by Lipoxygenase Reveals Steric Features of the Catalytic Mechanism. Biochemistry, 26, 6880–6884.

    Google Scholar 

  • Funk, M. O. Jr., Carroll, R. T., Thompson, J. F., Sands, R. H., and Dunham, W. R. (1990) Role of Iron in Lipoxygenase Catalysis. J. Am. Chem. Soc., 112, 5375–5376.

    Google Scholar 

  • Gaffney, B. J., Mavrophilipos, D. V., and Doctor, K. S. (1993) Access of Ligands to the Ferric Center in Lipoxygenase-1. Biophys J., 64, 773–783.

    Google Scholar 

  • Gajewski, J. J., Olson, L. P., and Tupper, K. J. (1993) Hydrogen-deuterium Fractionation for Hydrogen-sp2 Carbon Bonds in Olefins and Allyl Radicals. J. Am. Chem. Soc., 115, 4548–4553.

    Google Scholar 

  • Galey, J. B., Bombard, S., Chopard, C., Girerd, J. J., Lederer, F., Thang, D. C., Nam, N. H., Mansuy, D., and Chottard, J. C. (1988) Hexanal Phenylhydrazone is a Mechanism-based Inactivator of Soybean Lipoxygenase 1. Biochemistry, 27, 1058–1066.

    Google Scholar 

  • Gardner, H. W. (1989) Soybean Lipoxygenase-1 Enzymically Forms Both (9S)- and (13S)-Hydroperoxides from Linoleic Acid by a pH-Dependent Mechanism. Biochim. Biophys. Acta, 1001, 274–281.

    Google Scholar 

  • Gardner, H. W. (1991) Recent Investigations into the Lipoxygenase Pathway of Plants. Biochim. Biophys. Acta, 1084, 221–239.

    Google Scholar 

  • Garssen, G. J., Veldink, G. A., Vliegenthart, J. F. G., and Boldingh, J. (1976) The Formation of threo-11-Hydroxy-trans-12:13-epoxy-9-cis-octadecenoic Acid by Enzymic Isomerisation of 13-l-hydroperoxy-9-cis, 11-trans-Octadecadienoic Acid by Soybean Lipoxygenase-1. Eur. J. Biochem., 62, 33–36.

    Google Scholar 

  • Garssen, G. J., Vliegenthart, J. F. G., and Boldingh, J. (1972) The Origin and Structures of Dimeric Fatty Acids from the Anaerobic Reaction Between Soya-bean Lipoxygenase, Linoleic Acid and Its Hydroperoxide. Biochem. J., 130, 435–442.

    Google Scholar 

  • Glickman, M. H., Wiseman, J. S., and Klinman, J. P. (1994) Extremely Large Isotope Effects in the Soybean Lipoxygenase-linoleic Acid Reaction. J. Am. Chem. Soc., 116, 793–794.

    Google Scholar 

  • Gollnick, K., and Kuhn, H. J. (1979) Ene-reactions with Singlet Oxygen, in Singlet Oxygen (H. H. Wasserman, and R. W. Murray, Eds.), Academic Press, New York, pp. 287–429.

    Google Scholar 

  • Gorman, A. A., Hamblett, I., Lambert, C., Spencer, B., and Standen, M. C. (1988) Identification of Both Preequilibrium and Diffusion Limits for Reaction of Singlet Oxygen, O2 (1Δg), with Both Physical and Chemical Quenchers: Variable-temperature, Time-resolved Infrared Luminescence Studies. J. Am. Chem. Soc., 110, 8053–8059.

    Google Scholar 

  • Grdina, S. B., Orfanopoulos, M., and Stephenson, L. M. (1979) Stereochemical Dependence of Isotope Effects in the Singlet Oxygen-Olefin Reaction. J. Am. Chem. Soc., 101, 3111–3112.

    Google Scholar 

  • Green, I. G., and Walton, J. C. (1984) Electron Delocalization and Stabilization in Heptatrienyl and Polyenyl Radicals. J. Chem. Soc. Perkin Trans. 2, 1253–1257.

    Google Scholar 

  • Griller, D., and Ingold, K. U. (1980) Free-radical Clocks. Acc. Chem. Res., 13, 317–323.

    Google Scholar 

  • Grossman, S., Klein, B. P., Cohen, B., King, D., and Pinsky, A. (1984) Methylmercuric Iodide Modification of Lipoxygenase-1. Effects on the Anaerobic Reaction and Pigment Bleaching. Biochim. Biophys. Acta, 793, 455–462.

    Google Scholar 

  • Hamburg, M. (1971) Steric Analysis of Hydroperoxides Formed by Lipoxygenase Oxygenation of Linoleic Acid. Anal. Biochem., 43, 515–526.

    Google Scholar 

  • Hamberg, M., and Hamberg, G. (1980) On the Mechanism of the Oxygenation of Arachidonic Acid by Human Platelet Lipoxygenase. Biochem. Biophys. Res. Commun., 95, 1090–1097.

    Google Scholar 

  • Hamburg, M., and Samuelsson, B. (1967) On the Specificity of the Oxgen- ation of Unsaturated Fatty Acids Catalyzed by Soybean Lipoxygenase. J. Biol. Chem., 242, 5329–5335.

    Google Scholar 

  • Harding, L. B., and Goddard, W. A. I. (1980) The Mechanism of the Ene Reaction of Singlet Oxygen with Olefins. J. Am. Chem. Soc., 102, 439–449.

    Google Scholar 

  • Harpel, M. R., and Lipscomb, J. D. (1990) Gentisate 1,2-Dioxygenase from Pseudomonas. Substrate Coordination to Active Site Fe2+ and Mechanism of Turnover. J. Biol. Chem., 265, 22187–22196.

    Google Scholar 

  • Hatanaka, A., Kajiwara, T., Matsui, K., and Yamaguchi, M. (1989) Product Specificity in an Entire Series of (ω-6Z,ω-9)-C13~C20-Dienoic Acids and Dienols for Soybean Lipoxygenase. Z. Naturforsch., 44c, 64–70.

    Google Scholar 

  • Hatanaka, A., Kajiwara, T., Sekiya, J., and Asano, M. (1984) Product Specificity During Incubation of Methyl Linoeate with Soybean Lipoxygenase-1. Z. Naturforsch., 39c, 171–173.

    Google Scholar 

  • Hiatt, R. (1971) Hydroperoxides, in Organic Peroxides (D. Swern, Ed.), Wiley-Interscience, New York, pp. 1–152.

    Google Scholar 

  • Hildebrand, D. F., and Grayburn, W. S. (1991) Lipid Metabolites: Regulators of Plant Metabolism?, in Plant Biochemical Regulators (H. W. Gausman, Ed.), Marcel Dekker, New York, pp. 69–95.

    Google Scholar 

  • Holman, R. T., Egwim, P. O., and Christie, W. W. (1969) Substrate Specificity of Soybean Lipoxidase. J. Biol. Chem., 244, 1149–1151.

    Google Scholar 

  • Houk, K. N., Gustafson, S. M. E., and Black, K. A. (1992) Theoretical Secondary Kinetic Isotope Effects and the Interpretation of Transition State Geometries. 1. The Cope Rearrangement. J. Am. Chem. Soc., 114, 8565–8572.

    Google Scholar 

  • Hwang, C. C., and Grissom, C. B. (1994) Unusually Large Deuterium Isotope Effect in Soybean Lipoxygenase is Not Caused by a Magnetic Isotope Effect. J. Am. Chem. Soc. 116, 795–796.

    Google Scholar 

  • Iwahashi, H., Albro, P. W., Mcgown, S. R., Tomer, K. B., and Mason, R. P. (1991a) Isolation and Identification of Alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone Radical Adducts Formed by the Decomposition of the Hydroperoxides of Linoleic Acid, Linolenic Acid, and Arachidonic Acid by Soybean Lipoxygenase. Arch. Biochem. Biophys., 285, 172–180.

    Google Scholar 

  • Iwahashi, H., Parker, C. E., Mason, R. P., and Tomer, K. B. (1991b) Radical Adducts of Nitrosobenzene and 2-Methyl-2-nitrosopropane with 12, 13-Epoxylinoleic Acid Radical, 12,13-Epoxylinolenic Acid Radical and 14,15-Epoxyarachidonic Acid Radical. Identification by h.p.l.c.-e.p.r. and Liquid Chromatography-thermospraym.s. Biochem. J., 276, 447–453.

    Google Scholar 

  • Jovanovic, S. V., Jankovic, I., and Josimovic, L. (1992) Electron-transfer Reactions of Alkyl Peroxy Radicals. J. Am. Chem. Soc., 114, 9018–9021.

    Google Scholar 

  • Kanofsky, J. R., and Axelrod, B. (1986) Singlet Oxygen Production by Soybean Lipoxygenase Isozymes. J. Biol. Chem., 261, 1099–1104.

    Google Scholar 

  • Korth, H.-G., Trill, H., and Sustmann, R. (1981) [1-2H]Allyl Radical: Barrier to Rotation and Allyl Delocalization Energy. J. Am. Chem. Soc., 103, 4483–4489.

    Google Scholar 

  • Kuhn, H., Eggert, L., Zabolotsky, O. A., Myagkova, G. I., and Schewe, T. (1991) Keto Fatty Acids Not Containing Doubly Allylic Methylenes Are Lipoxygenase Substrates. Biochemistry, 30, 10269–10273.

    Google Scholar 

  • Kuhn, H., Heydeck, D., Wiesnaer, R., and Schewe, T. (1985) The Positional Specificity of Wheat Lipoxygenase; the Carboxyl Group as a Signal for the Recognition of the Site of the Hydrogen Removal. Biochim. Biophys. Acta, 830, 25–29.

    Google Scholar 

  • Kuhn, H., Holzhutter, H.-G., Schewe, T., Hiebsch, C., and Rapoport, S. M. (1984) The Mechanism of Inactivation of Lipoxygenases by Acetylenic Fatty Acids. Eur. J. Biochem., 139, 577–583.

    Google Scholar 

  • Lee-Ruff, E. (1977) The Organic Chemistry of Superoxide. Chem. Soc. Rev., 6, 195–214.

    Google Scholar 

  • MacInnes, I., and Walton, J. C. (1985) Rotational Barriers in Pentadienyl and Pent-2-en-4-ynyl Radicals. J. Chem. Soc. Perkin Trans. 2, 1073–1076.

    Google Scholar 

  • Matsuda, S., Suzuki, H., Yoshimoto, T., Yamamoto, S., and Miyatake, A. (1991) Analysis of Non-heme Iron in Arachidonate 12-Lipoxygenase of Porcine Leukocytes. Biochim. Biophys. Acta, 1084, 202–204.

    Google Scholar 

  • Mcmillan, R. M., and Walker, E. R. H. (1992) Designing Therapeutically Effective 5-Lipoxygenase Inhibitors. Trends Pharmacol. Sci., 13, 323–330.

    Google Scholar 

  • Michaud-Soret, I., and Chottard, J. C. (1992) Investigation of Sulfur Containing Amino Acids at the Lipoxygenase Active Site Using a Platinum Complex. Biochem. Biophys. Res. Commun., 182, 779–785.

    Google Scholar 

  • Minor, W., Steczko, J., Bolin, J. T., Otwinowski, Z., and Axelrod, B. (1993) Crystallographic Determination of the Active-site Iron and Its Ligands in Soybean Lipoxygenase. Biochemistry, 32, 6320–6323.

    Google Scholar 

  • Murray, R. W. (1979) Chemical Sources of Singlet Oxygen, in Singlet Oxygen (H. H. Wasserman and R. W. Murray, Eds.), Academic Press, New York, pp. 59–114.

    Google Scholar 

  • Navaratnam, S., Feiters, M. C., Al-Hakim, M., Allen, J. C., Veldink, G. A., and Vliegenthart, J. F. G. (1988) Iron Environment in Soybean Lipoxygenase-1. Biochim. Biophys. Acta, 956, 70–76.

    Google Scholar 

  • Nelson, M. J. (1987) The Nitric Oxide Complex of Ferrous Soybean Lipoxygenase-1. J. Biol. Chem., 262, 12137–12142.

    Google Scholar 

  • Nelson, M. J. (1988a) Catecholate Complexes of Ferric Soybean Lipoxygenase1. Biochemistry, 27, 4273–4278.

    Google Scholar 

  • Nelson, M. J. (1988b) Evidence for Water Coordinated to the Active Site Iron in Soybean Lipoxygenase-1. J. Am. Chem. Soc., 110, 2985–2986.

    Google Scholar 

  • Nelson, M. J., Batt, D. G., Thompson, J. S., and Wright, S. W. (1991) Reduction of the Active-site Iron by Potent Inhibitors of Lipoxygenases. J. Biol. Chem., 266, 8225–8229.

    Google Scholar 

  • Nelson, M. J., and Cowling, R. A. (1990) Observation of a Peroxyl Radical in Samples of “Purple” Lipoxygenase. J. Am. Chem. Soc., 112, 2820–2821.

    Google Scholar 

  • Nelson, M. J., Seitz, S. P., and Cowling, R. A. (1990) Enzyme-bound Pentadienyl and Peroxyl Radicals in Purple Lipoxygenase. Biochemistry, 29, 6897–6903.

    Google Scholar 

  • Nelson, M. J., Cowling, R. A., and Seitz, S. P. (1994) Structural Characterization of Alkyl and Peroxyl Radicals in Solutions of Purple Lipoxygenase. Biochemistry, 33, 4966–4973.

    Google Scholar 

  • Nguyen, T., Falgueyret, J.-P., Abramovitz, M., and Riendeau, D. (1991) Evaluation of the Role of Conserved His and Met Residues Among Lipoxygenases by Site-directed Mutagenesis of Recombinant Human 5-Lipoxygenase. J. Biol. Chem., 266, 22057–22062.

    Google Scholar 

  • Nikolaev, V., Reddanna, P., Whelan, J., Hildenbrandt, G., and Reddy, C. C. (1990) Stereochemical Nature of the Products of Linoleic Acid Oxidation Catalyzed by Lipoxygenases from Potato and Soybean. Biochem. Biophys. Res. Commun., 170, 491–496.

    Google Scholar 

  • Nishida, Y., and Akamatsu, T. (1991) Model Compounds for Purple Lipoxygenase. Chem. Lett., 2013–2016.

    Google Scholar 

  • Orfanopoulos, M., Smonou, I., and Foote, C. S. (1990) Intermediates in the Ene Reactions of Singlet Oxygen and N-phenyl-1,2,4-triazoline-3,5-dione with Olefins. J. Am. Chem. Soc., 112, 3607–3614.

    Google Scholar 

  • Ortiz De Montellano, P. R. (1986) Cytochrome P-450: Structure, Mechanism, and Biochemistry, Plenum Press, New York.

    Google Scholar 

  • Ortiz De Montellano, P. R., and Stearns, R. A. (1987) Timing of the Radical Recombination Step in Cytochrome P-450 Catalysis with Ringstrained Probes. J. Am. Chem. Soc., 109, 3415–3420.

    Google Scholar 

  • Orville, A. M., Chen, V. J., Kriauciunas, A., Harpel, M. R., Fox, B. G., Münck, E., and Lipscomb, J. D. (1992) Thiolate Ligation of the Active Site Fe2+ of Isopenicillin N Synthase Derives from Substrate Rather Than Endogenous Cysteine: Spectroscopic Studies of Site-specific Cys → Ser Mutated Enzymes. Biochemistry, 31, 4602–4612.

    Google Scholar 

  • Pavlosky, M. A., and Solomon, E. I. (1994) Near-Ir Cd/Mcd Spectral Elucidation of Two Forms of the Non-heme Active Site in Native Ferrous Soybean Lipoxygenase 1: Correlation to Crystal Structures and Reactivity. J. Am. Chem. Soc. 116, 11610–11611.

    Google Scholar 

  • Percival, M. D. (1991) Human 5-Lipoxygenase Contains an Essential Iron. J. Biol. Chem., 266, 10058–10061.

    Google Scholar 

  • Petersson, L., Slappendel, S., Feiters, M. C., and Vleigenthart, J. F. G. (1987) Magnetic Susceptibility Studies on Yellow and Anaerobically Substrate-treated Yellow Soybean Lipoxygenase-1. Biochim. Biophys. Acta, 913, 228–237.

    Google Scholar 

  • Petersson, L., Slappendel, S., and Vliegenthart, J. F. G. (1985) The Magnetic Susceptibility of Native Soybean Lipoxygenase-1. Implications for the Symmetry of the Iron Environment and the Possible Coordination of Dioxygen to Fe(II). Biochim. Biophys. Acta, 828, 81–85.

    Google Scholar 

  • Pistorius, E. K., Axelrod, B., and Palmer, G. (1976) Evidence for the Participation of Iron in Lipoxygenase Reaction from Optical and Electron Spin Resonance Studies. J. Biol. Chem., 251, 7144–7148.

    Google Scholar 

  • Porter, N. A. (1986) Mechanisms for the Autoxidation of Polyunsaturated Lipids. Acc. Chem. Res., 19, 262–268.

    Google Scholar 

  • Porter, N. A., Lehman, L. S., Weber, B. A., and Smith, K. J. (1981) Unified Mechanism for Polyunsaturated Fatty Acid Autoxidation. Competition of Peroxy Radical Hydrogen Atom Abstraction, β-Scission, and Cyclization. J. Am. Chem. Soc., 103, 6447–6455.

    Google Scholar 

  • Que, L., Jr., Lauffer, R. B., Lynch, J. B., Murch, B. P., and Pyrz, J. W. (1987) Elucidation of the Coordination Chemistry of the Enzyme-Substrate Complex of Catechol 1,2-Dioxygenase by NMR Spectroscopy. J. Am. Chem. Soc., 109, 5381–5385.

    Google Scholar 

  • Ramachandran, S., Carroll, R. T., Dunham, W. R. and Funk, M. O., Jr., (1992) Limited Proteolysis and Active-site Labelling Studies of Soybean Lipoxygenase-1. Biochemistry, 31, 7700–7706.

    Google Scholar 

  • Randall, C. R., Zang, Y., True, A. E., Que, L., Jr., Charnock, J. M., Garner, C. D., Fujishima, Y., Schofield, C. J., and Baldwin, J. E. (1993) X-ray Absorption Studies of the Ferrous Active Site of Isopenicillin N Synthase and Related Model Complexes. Biochemistry, 32, 6664–6673.

    Google Scholar 

  • Rapoport, S., Härtel, B., and Hausdorf, G. (1984) Methionine Sulfoxide Formation: The Cause of Self-inactivation of Reticulocyte Lipoxygenase. Eur. J. Biochem., 139, 573–576.

    Google Scholar 

  • Rotenberg, S. A., Grandizio, A. M., Selzer, A. T., and Clapp, C. H. (1988) Inactivation of Soybean Lipoxygenase 1 by 12-Iodo-cis-9-octadecenoic Acid. Biochemistry, 27, 8813–8818.

    Google Scholar 

  • Samuelsson, B. E., Dahlén, S.-E., Lindgren, J. A., Rouzer, C. A., and Serhan, C. N. (1987) Leukotrienes and Lipoxins: Structures, Biosynthesis, and Biological Effects. Science (Washington, D. C.), 237, 1171–1176.

    Google Scholar 

  • Scarrow, R. C., Trimitsis, M. G., Buck, C. P., Grove, G. N., Cowling, R. A., and Nelson, M. J. (1994) X-ray Spectroscopy of the Iron Site in Soybean Lipoxygenase-1: Changes in Coordination Upon Oxidation or Addition of Methanol. Biochemistry 33, 15023–15035.

    Google Scholar 

  • Schewe, T., and Kühn, H. (1991) Do 15-Lipoxygenases Have a Common Biological Role? Trends Biochem. Sci., 16, 369–373.

    Google Scholar 

  • Schewe, T., Kuhn, H., and Rapoport, S. M. (1986) Positional Specificity of Lipoxygenases and Their Suitability for Testing Potential Drugs. Prost. Leukot. Med., 23, 155–160.

    Google Scholar 

  • Schilstra, M. J., Veldink, G. A., Verhagen, J., and Vliegenthart, J. F. G. (1992) Effect of Lipid Hydroperoxide on Lipoxygenase Kinetics. Biochemistry, 31, 7692–7699.

    Google Scholar 

  • Schilstra, M. J., Veldink, G. A., and Vliegenthart, J. F. G. (1993) Kinetic Analysis of the Induction Period in Lipoxygenase Catalysis. Biochemistry, 32, 7686–7691.

    Google Scholar 

  • Shibata, D., Steczko, J., Dixon J. E., Andrews, P. C., Hermodson, M. and Axelrod, B. (1988) Primary Structure of Soybean Lipoxygenase L-2. J. Biol. Chem., 263, 6816–6821.

    Google Scholar 

  • Shibata, D., Steczko, J., Dixon, J. E., Hermodson, M., Yazdanparast, R., and Axelrod, B. (1987) Primary Structure of Soybean Lipoxygenase-1. J. Biol. Chem., 262, 10080–10085.

    Google Scholar 

  • Siedow, J. N. (1991) Plant Lipoxygenase: Structure and Function. Annu. Rev. Plant Physiol. Plant Mol. Biol., 42, 145–188.

    Google Scholar 

  • Sigal, E., Craik, C. S., Highland, E., Grunberger, D., Costello, L. L., Dixon, R. A. F., and Nadel, J. A. (1988) Molecular Cloning and Primary Structure of Human 15-Lipoxygenase. Biochem. Biophys. Res. Commun., 157, 457–464.

    Google Scholar 

  • Slappendel, S., Aasa, R., Malmström, B. G., Verhagen, J., Veldink, G. A., and Vliegenthart, J. F. G. (1982a) Factors Affecting the Line-shape of the EPR Signal of High-spin Fe(III) in Soybean Lipoxygenase. Biochim. Biophys. Acta, 708, 259–265.

    Google Scholar 

  • Slappendel, S., Malmström, B. G., Petersson, L., Ehrenberg, A., Veldink, G. A., and Vliegenthart, J. F. G. (1982b) On the Spin and Valence State of the Iron in Native Soybean Lipoxygenase-1. Biochem. Biophys. Res. Commun., 708, 673–677.

    Google Scholar 

  • Slappendel, S., Veldink, G. A., Vliegenthart, J. F. G., Aasa, R., and Malmström, B. G. (1983) A Quantitative Optical and EPR Study on the Interaction Between Soybean Lipoxygenase-1 and 13-L-hydro-peroxylinoleic Acid. Biochim. Biophys. Acta, 747, 32–36.

    Google Scholar 

  • Sloane, D. L., Leung, R., Craik, C. S., and Sigal, E. (1991) A Primary Determinant for Lipoxygenase Positional Specificity. Nature, 354, 149–152.

    Google Scholar 

  • Smith, W. L., and Marnett, L. J. (1991) Prostaglandin Endoperoxide Synthase: Structure and Catalysis. Biochim. Biophys. Acta, 1083, 1–17.

    Google Scholar 

  • Spaapen, L. J. M., Veldink, G. A., Liefkins, T. J., Vliegenthart, J. F. G., and Kay, C. M. (1979) Circular Dichroism of Lipoxygenase-1 from Soybeans. Biochim. Biophys. Acta, 574, 301–311.

    Google Scholar 

  • Spaapen, L. J. M., Verhagen, J., Veldink, G. A., and Vliegenthart, J. F. G. (1980) The Effect of Modification of Sulfhydryl Groups in Soybean Lipoxygenase-1. Biochim. Biophys. Acta, 618, 153–162.

    Google Scholar 

  • Steczko, J., and Axelrod, B. (1992) Identification of the Iron-binding Histidine Residues in Soybean Lipoxygenase-1. Biochem. Biophys. Res. Commun., 186, 686–689.

    Google Scholar 

  • Steczko, J., Donoho, G. P., Clemens, J. C., Dixon, J. E., and Axelrod, B. (1992) Conserved Histidine Residues in Soybean Lipoxygenase: Functional Consequences of Their Replacement. Biochemistry, 31, 4053–4057.

    Google Scholar 

  • Stubbe, J. (1990) Ribonucleotide Reductases: Amazing and Confusing. J. Biol. Chem., 265, 5329–5332.

    Google Scholar 

  • Swern, D. (1979) Peroxides, in Comprehensive Organic Chemistry (J. F. Stoddart, Ed.), Pergamon Press, New York, pp. 909–940.

    Google Scholar 

  • Tsai, A. L., Palmer, G., and Kulmacz, R. J. (1992) Prostaglandin H Synthase: Kinetics of Tyrosyl Radical Formation and of Cyclooxygenase Catalysis. J. Biol. Chem., 267, 17753–17759.

    Google Scholar 

  • Van Der Heijdt, L. M., Feiters, M. C., Navaratnam, S., Nolting, H.-F., Hermes, C., Veldink, G. A., and Vliegenthart, J. F. G. (1992) X-ray Absorption Spectroscopy of Soybean Lipoxygenase-1. Influence of Lipid Hydroperoxide Activation and Lyophilization on the Structure of the Non-heme Iron Active Site. Eur. J. Biochem., 207, 793–802.

    Google Scholar 

  • Van Eldik, R., Cohen, H., and Meyerstein, D. (1994) Ligand Interchange Controls Many Oxidations of Divalent First-Row Transition Metal Ions by Free Radicals. Inorg. Chem. 33, 1566–1568.

    Google Scholar 

  • Veldink, G. A., Garssen, G. J., Vliegenthart, J. F. G., and Boldingh, J. (1972) Positional Specificity of Corn Germ Lipoxygenase as a Function of pH. Biochem. Biophys. Res. Commun., 47, 22–26.

    Google Scholar 

  • Veldink, G. A., and Vliegenthart, J. F. (1984) Lipoxygenases, Nonheme Iron-containing Enzymes. Adv. Inorg. Biochem., 6, 139–161.

    Google Scholar 

  • Volker Wagner, A. F., Frey, M., Neugebauer, F. A., Schäfer, W., and Knappe, J. (1992) The Free Radical in Pyruvate Formate-lyase is Located on Glycine-734. Proc. Natl. Acad. Sci. U.S.A., 89, 996–1000.

    Google Scholar 

  • Walling, C. (1995) Liquid Phase Autoxidation, in Active Oxygen in Chemistry (C. S. Foote, J. S. Valentine, A. Greenberg, and J. F. Liebman, Eds.), Chapman & Hall, New York, pp. 24–65.

    Google Scholar 

  • Wang, Z. X., Killilea, S. D., and Srivastava, D. K. (1993) Kinetic Evaluation of Substrate-dependent Origin of the Lag Phase in Soybean Lipoxygenase-1 Catalyzed Reactions. Biochemistry, 32, 1500–1509.

    Google Scholar 

  • Wasserman, M. A., Smith, E. F., Iii, Underwood, D. C., and Barnette, M. A. (1991) Pharmacology and Pathophysiology of 5-Lipoxygenase Products, in Lipoxygenases and Their Products (S. T. Crooke and A. Wong, Eds.), Academic Press, San Diego, pp. 1–50.

    Google Scholar 

  • Whittaker, J. W., and Solomon, E. I. (1988) Spectroscopic Studies on Ferrous Non-heme Iron Active Sites: MCD of Mononuclear Sites in Superoxide Dismutase and Lipoxygenase. J. Am. Chem. Soc., 110, 5329–5339.

    Google Scholar 

  • Wilkins, P. C., Dalton, H., Podmore, I. D., Deighton, N., and Symons, M. C. R. (1992) Biological Methane Activation Requires the Intermediacy of Carbon-centered Radicals. Eur. J. Biochem., 210, 67–72.

    Google Scholar 

  • Wiseman, J. S. (1989) Alpha-secondary Isotope Effects in the Lipoxygenase Reaction. Biochemistry, 28, 2106–2111.

    Google Scholar 

  • Wiseman, J. S., and Nichols, J. S. (1988) Ketones as Electrophilic Substrates of Lipoxygenase. Biochem. Biophys. Res. Commun., 154, 544–549.

    Google Scholar 

  • Wiseman, J. S., Skoog, M. T., and Clapp, C. H. (1988) Activity of Soybean Lipoxygenase in the Absence of Lipid Hydroperoxide. Biochemistry, 27, 8810–8813.

    Google Scholar 

  • Wright, S. W., and Nelson, M. J. (1992) Episulfide Inhibitors of Lipoxygenase. Bioorg. Med. Chem. Lett., 2, 1385–1390.

    Google Scholar 

  • Yamaguchi, K., Yabushita, S., and Fueno, T. (1981a) Geometry Optimizations of the Dioxetane, Perepoxide and 1,4-Diradicals for the Ethylene Plus Molecular Oxygen System: Mechanism of Photooxygenation of Olefins. Chem. Phys. Lett., 78, 572–577.

    Google Scholar 

  • Yamaguchi, K., Yabushita, S., Fueno, T., and Houk, K. N. (1981b) Mechanism of Photooxygenation Reactions. Computational Evidence Against the Diradical Mechanism of Singlet Oxygen Ene Reactions. J. Am. Chem. Soc., 103, 5043–5046.

    Google Scholar 

  • Zang, Y., Elgren, T. E., Dong, Y., and Que, L., Jr. (1993) A High-potential Ferrous Complex and Its Conversion to an Alkylperoxoiron(III) Intermediate. A Lipoxygenase Model. J. Am. Chem. Soc., 115, 811–813.

    Google Scholar 

  • Zhang, Y., Gebhard, M. S., and Solomon, E. I. (1991) Spectroscopic Studies of the Non-heme Ferric Active Site in Soybean Lipoxygenase: Magnetic Circular Dichroism as a Probe of Electronic and Geometric Structure. Ligand-field Origin of Zero-field Splitting. J. Am. Chem. Soc., 113, 5162–5175.

    Google Scholar 

  • Zhang, Y. Y., Rådmark, O., and Samuelsson, B. (1992) Mutagenesis of Some Conserved Residues in Human 5-Lipoxygenase; Effects on Enzyme Ac tivity. Proc. Natl. Acad. Sci. U.S.A., 89, 485–489.

    Google Scholar 

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Authors
  1. Mark J. Nelson
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  2. Steven P. Seitz
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Editors and Affiliations

  1. University of California, Los Angeles, USA

    Joan Selverstone Valentine  & Christopher S. Foote  & 

  2. University of North Carolina at Charlotte, USA

    Arthur Greenberg

  3. University of Maryland Baltimore County, USA

    Joel F. Liebman

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Nelson, M.J., Seitz, S.P. (1995). The Mechanism of Lipoxygenases. In: Valentine, J.S., Foote, C.S., Greenberg, A., Liebman, J.F. (eds) Active Oxygen in Biochemistry. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-9783-0_6

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