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Secondary Alkyl Hydroperoxides as Inhibitors and Alternate Substrates for Lipoxygenase
Author(s) -
Decker Ilka,
Waller Tiffany,
Frisch Jonathan,
Funk Max
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.643.2
Subject(s) - chemistry , lipoxygenase , alkyl , isothermal titration calorimetry , yield (engineering) , substrate (aquarium) , cumene hydroperoxide , organic chemistry , homolysis , enzyme , photochemistry , radical , biochemistry , catalysis , materials science , oceanography , metallurgy , geology
In polyunsaturated fatty acid metabolism, lipoxygenase catalyses the reaction of membrane‐derived lipids with molecular oxygen to yield hydroperoxides. Lipoxygenase needs to be activated by its own peroxide products via a redox mechanism that converts the enzyme's non‐heme iron co‐factor from an iron (II) state is to its active iron (III) form. To better understand the activation mechanism, the reaction of soybean lipoxygenase‐1 with secondary alkyl hydroperoxides was analyzed. The small molecule peroxides mimicked the hydrophobic end of the hydroperoxide product. While the reaction rates were found to follow the same kinetic mechanism as the hydroperoxide products, the secondary alkyl hydroperoxides inhibited the enzyme especially at high substrate concentration. Molecules with greater chain length were more effective inhibitors and proved to be more efficient in oxidation of the iron during EPR measurements. Isothermal titration calorimetry experiments showed a constant heat output in the reaction of lipoxygenase‐1 with the hydroperoxides. In this reaction, the hydroperoxides were converted to the corresponding carbonyl compounds via homolytic dehydration. We will also report on the characterization of the newly discovered reaction.