Formation of free radical metabolites in the reaction between soybean lipoxygenase and its inhibitors. An ESR study.
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.
Van der Zee
J
J
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Eling
T E
TE
Mason
R P
RP
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
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