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The Mechanism of Lipoxygenases

  • Mark J. Nelson
  • Steven P. Seitz

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.

Keywords

Linoleic Acid Electron Paramagnetic Resonance Kinetic Isotope Effect Fatty Acid Radical Nonheme Iron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 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
  2. 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
  3. Baldwin, J. E., and Bradley, M. (1990) Isopenicillin N Synthase: Mechanistic Studies. Chem. Rev., 90, 1079–1088.Google Scholar
  4. Batt, D. G. (1992) 5-Lipoxygenase Inhibitors and Their Anti-inflammatory Activities. Prog. Med. Chem., 29, 1–63Google Scholar
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Clapp, C. H., Banerjee, A., and Rotenberg, S. A. (1985) Inhibition of Soybean Lipoxygenase 1 by N-alkylhydroxylamines. Biochemistry, 24, 1826–1830.Google Scholar
  14. Corey, E. J. (1987) Enzymic Lipoxygenation of Arachidonic Acid: Mechanism, Inhibition, and Role in Eicosanoid Biosynthesis. Pure Appl. Chem., 59, 269–278.Google Scholar
  15. 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
  16. 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
  17. Corey, E. J., and Mehrotra, M. M. (1983) Stereochemistry of the Lipoxygenase-catalyzed Allylic Hydroperoxide → Oxiranylcarbinol Rearrangement. Tetrahedron Lett., 24, 4921–4922.Google Scholar
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. Dussault, M. H., and Hayden, M. R. (1992) Auxiliary-directed Dioxygenation: Stereoselective Synthesis of a Diene Hydroperoxide. Tetrahedron Lett., 33, 443–446.Google Scholar
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. Gardner, H. W. (1991) Recent Investigations into the Lipoxygenase Pathway of Plants. Biochim. Biophys. Acta, 1084, 221–239.Google Scholar
  45. 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
  46. 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
  47. 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
  48. 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
  49. 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
  50. 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
  51. 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
  52. Griller, D., and Ingold, K. U. (1980) Free-radical Clocks. Acc. Chem. Res., 13, 317–323.Google Scholar
  53. 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
  54. Hamburg, M. (1971) Steric Analysis of Hydroperoxides Formed by Lipoxygenase Oxygenation of Linoleic Acid. Anal. Biochem., 43, 515–526.Google Scholar
  55. 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
  56. 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
  57. 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
  58. 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
  59. 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
  60. 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
  61. Hiatt, R. (1971) Hydroperoxides, in Organic Peroxides (D. Swern, Ed.), Wiley-Interscience, New York, pp. 1–152.Google Scholar
  62. 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
  63. Holman, R. T., Egwim, P. O., and Christie, W. W. (1969) Substrate Specificity of Soybean Lipoxidase. J. Biol. Chem., 244, 1149–1151.Google Scholar
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. Kanofsky, J. R., and Axelrod, B. (1986) Singlet Oxygen Production by Soybean Lipoxygenase Isozymes. J. Biol. Chem., 261, 1099–1104.Google Scholar
  70. 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
  71. 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
  72. 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
  73. 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
  74. Lee-Ruff, E. (1977) The Organic Chemistry of Superoxide. Chem. Soc. Rev., 6, 195–214.Google Scholar
  75. 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
  76. 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
  77. Mcmillan, R. M., and Walker, E. R. H. (1992) Designing Therapeutically Effective 5-Lipoxygenase Inhibitors. Trends Pharmacol. Sci., 13, 323–330.Google Scholar
  78. 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
  79. 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
  80. 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
  81. 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
  82. Nelson, M. J. (1987) The Nitric Oxide Complex of Ferrous Soybean Lipoxygenase-1. J. Biol. Chem., 262, 12137–12142.Google Scholar
  83. Nelson, M. J. (1988a) Catecholate Complexes of Ferric Soybean Lipoxygenase1. Biochemistry, 27, 4273–4278.Google Scholar
  84. 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
  85. 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
  86. 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
  87. 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
  88. 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
  89. 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
  90. 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
  91. Nishida, Y., and Akamatsu, T. (1991) Model Compounds for Purple Lipoxygenase. Chem. Lett., 2013–2016.Google Scholar
  92. 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
  93. Ortiz De Montellano, P. R. (1986) Cytochrome P-450: Structure, Mechanism, and Biochemistry, Plenum Press, New York.Google Scholar
  94. 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
  95. 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
  96. 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
  97. Percival, M. D. (1991) Human 5-Lipoxygenase Contains an Essential Iron. J. Biol. Chem., 266, 10058–10061.Google Scholar
  98. 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
  99. 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
  100. 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
  101. Porter, N. A. (1986) Mechanisms for the Autoxidation of Polyunsaturated Lipids. Acc. Chem. Res., 19, 262–268.Google Scholar
  102. 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
  103. 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
  104. 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
  105. 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
  106. 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
  107. 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
  108. 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
  109. 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
  110. Schewe, T., and Kühn, H. (1991) Do 15-Lipoxygenases Have a Common Biological Role? Trends Biochem. Sci., 16, 369–373.Google Scholar
  111. 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
  112. 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
  113. 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
  114. 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
  115. 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
  116. Siedow, J. N. (1991) Plant Lipoxygenase: Structure and Function. Annu. Rev. Plant Physiol. Plant Mol. Biol., 42, 145–188.Google Scholar
  117. 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
  118. 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
  119. 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
  120. 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
  121. 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
  122. Smith, W. L., and Marnett, L. J. (1991) Prostaglandin Endoperoxide Synthase: Structure and Catalysis. Biochim. Biophys. Acta, 1083, 1–17.Google Scholar
  123. 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
  124. 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
  125. 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
  126. 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
  127. Stubbe, J. (1990) Ribonucleotide Reductases: Amazing and Confusing. J. Biol. Chem., 265, 5329–5332.Google Scholar
  128. Swern, D. (1979) Peroxides, in Comprehensive Organic Chemistry (J. F. Stoddart, Ed.), Pergamon Press, New York, pp. 909–940.Google Scholar
  129. 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
  130. 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
  131. 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
  132. 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
  133. Veldink, G. A., and Vliegenthart, J. F. (1984) Lipoxygenases, Nonheme Iron-containing Enzymes. Adv. Inorg. Biochem., 6, 139–161.Google Scholar
  134. 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
  135. 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
  136. 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
  137. 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
  138. 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
  139. 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
  140. Wiseman, J. S. (1989) Alpha-secondary Isotope Effects in the Lipoxygenase Reaction. Biochemistry, 28, 2106–2111.Google Scholar
  141. Wiseman, J. S., and Nichols, J. S. (1988) Ketones as Electrophilic Substrates of Lipoxygenase. Biochem. Biophys. Res. Commun., 154, 544–549.Google Scholar
  142. 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
  143. Wright, S. W., and Nelson, M. J. (1992) Episulfide Inhibitors of Lipoxygenase. Bioorg. Med. Chem. Lett., 2, 1385–1390.Google Scholar
  144. 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
  145. 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
  146. 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
  147. 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
  148. 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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© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Mark J. Nelson
  • Steven P. Seitz

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