TAILIEUCHUNG - Báo cáo khoa học: Dual role of oxygen during lipoxygenase reactions

Studying the oxygenation kinetics of (19R⁄S,5Z,8Z,11Z,14Z)-19-hydroxy-eicosa-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. | ềFEBS Journal Dual role of oxygen during lipoxygenase reactions Igor Ivanov1 2 Jan Saam1 Hartmut Kuhn1 and Hermann-Georg Holzhutter1 1 Institute of Biochemistry Humboldt University MedicalSchoolCharite Berlin Germany 2 . Lomonosov State Academy of Fine ChemicalTechnology Moscow Russian Federation Keywords atherosclerosis eicosanoids enzymology inflammation osteoporosis reaction kinetics Correspondence . Holzhutter Institute of Biochemistry Charity-University Medicine Berlin Monbijoustr. 2 10117 Berlin Germany Fax 49 30 450 528905 Tel 49 30 450 528040 E-mail hergo@ Received 8 February 2005 revised 7 March 2005 accepted 21 March 2005 doi Studying the oxygenation kinetics of 19R S 5Z 8Z 11Z 14Z -19-hydroxy-eicosa-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

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