title: Formation of free radical metabolites in the reaction between soybean lipoxygenase and its inhibitors. An ESR study.
abstract: Recent studies showed that soybean lipoxygenase inhibitors like phenidone and nordihydroguaiaretic acid (NDGA) reduce the catalytically active ferric lipoxygenase to its inactive ferrous form. Addition of 13(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid (13-HPOD) regenerated the active ferric form. In this paper, it is shown that in such a system the inhibitors are oxidized to free-radical metabolites. Incubation of soybean lipoxygenase and linoleic acid with p-aminophenol, catechol, hydroquinone, NDGA, or phenidone resulted in the formation of the one-electron oxidation products of these compounds. Free-radical formation depended upon the presence of the lipoxygenase and 13-HPOD. The free radicals were detected by ESR spectroscopy, and their structure was confirmed by analysis of the spectra, using a computer correlation technique. These data support the proposed mechanism for the inhibition of lipoxygenase by phenolic antioxidants.
authors.affiliation: Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: J
authors.initials: J
authors.lastname: Van der Zee
authors.forename: T E
authors.initials: TE
authors.lastname: Eling
authors.forename: R P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000627:Aminophenols / Q000378:metabolism; D002396:Catechols / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006873:Hydroquinones / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism / Q000494:pharmacology; D008054:Lipid Peroxides; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000378:metabolism; D010084:Oxidation-Reduction; D013025:Glycine max / Q000201:enzymology; D013057:Spectrum Analysis
chemical_list: D000627:Aminophenols; D002396:Catechols; D005609:Free Radicals; D006873:Hydroquinones; D008041:Linoleic Acids; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D009637:Masoprocol; D008084:Lipoxygenase