The lipoxygenase activity of myoglobin. Oxidation of linoleic acid by the ferryl oxygen rather than protein radical.

摘要: Linoleic (9(Z),12(Z)-octadecadienoic) acid is oxidized by sperm whale myoglobin and H2O2 to an 84:16 (9S):(9R) enantiomer mixture of 9-hydroperoxy-10(E),12(Z)-octadecadienoic acid. Neither the 9,10- nor 12,13-epoxide linoleic acid, 9-hydroxy-10(E),12(Z)-octadecadienoic 13-hydroperoxy-9(Z),11(E)-octadeca-dienoic acids, detectably formed. Incubations with [(11R)-2H]- [(11S)-2H]linoleic acids indicate that pro-R hydrogen abstracted 76% time. An H64V mutant in which access heme crevice increased oxidizes exclusively abstraction give (9S)-hydroperoxide. Spectroscopic studies show Kd value for binding similar Km its oxidation reduces ferryl species ferric state. The stereochemical results, supported 18O-labeling studies, definitively rule out a significant role singlet oxygen myoglobin-catalyzed, H2O2-dependent protein radical formed also plays no part reaction because Vmax values are native two mutants (K102Q/Y103F/Y146F/Y151F H64V/K102Q/Y103F/Y146F/Y151F) tyrosine residues. Furthermore, rate formation 9-hydroperoxide not changed if allowed decay before added. results establish within rather than radical. They indicate, furthermore, addition occur antarafacial manner suggest specific model active site.