title: Dual role of oxygen during lipoxygenase reactions.
abstract: Studying the oxygenation kinetics of (19R/S,5Z,8Z,11Z,14Z)-19-hydroxyeicosa-5,8,11,14-tetraenoic acid (19-OH-AA) by rabbit 15-lipoxygenase-1 we observed a pronounced oxygen dependence of the reaction rate, which was not apparent with arachidonic acid as substrate. Moreover, we found that peroxide-dependent activation of the lipoxygenase depended strongly on the oxygen concentration. These data can be described with a kinetic model that extends previous schemes of the lipoxygenase reaction in three essential aspects: (a) the product of 19-OH-AA oxygenation is a less effective lipoxygenase activator than (13S,9Z,11E)-13-hydroperoxyoctadeca-9,11-dienoic acid; (b) molecular dioxygen serves not only as a lipoxygenase substrate, but also impacts peroxide-dependent enzyme activation; (c) there is a leakage of radical intermediates from the catalytic cycle, which leads to the formation of inactive ferrous lipoxygenase. This enzyme inactivation can be reversed by another round of peroxide-dependent activation. Taken together our data indicate that both peroxide activation and the oxygen affinity of lipoxygenases depend strongly on the chemistry of the lipid substrate. These findings are of biological relevance as variations of the reaction conditions may turn the lipoxygenase reaction into an efficient source of free radicals.
authors.affiliation: Institute of Biochemistry Humboldt University Medical School Charité, Berlin, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Ivanov
authors.forename: Jan
authors.initials: J
authors.lastname: Saam
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kuhn
authors.forename: Hermann-Georg
authors.initials: HG
authors.lastname: Holzhütter
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D008041:Linoleic Acids / Q000378:metabolism; D008042:Linolenic Acids / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008433:Mathematics; D008962:Models, Theoretical; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits
chemical_list: D008041:Linoleic Acids; D008042:Linolenic Acids; D008054:Lipid Peroxides; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D016718:Arachidonic Acid; C064441:13-oxo-9,11-octadecadienoic acid; D001093:Arachidonate 15-Lipoxygenase; D010100:Oxygen