标题：Catalytic Production of Oxo-fatty Acids by Lipoxygenases Is Mediated by the Radical–Radical Dismutation between Fatty Acid Alkoxyl Radicals and Fatty Acid Peroxyl Radicals in Fatty Acid Assembly
摘要：Oxo-octadecadienoic acids (OxoODEs) act as peroxisome proliferator-activated receptor (PPAR) agonists biologically, and are known to be produced in the lipoxygenase/linoleate system. OxoODEs seem to originate from the linoleate alkoxyl radicals that are generated from ( E / Z )-hydroperoxy octadecadienoic acids (( E / Z )-HpODEs) by a pseudoperoxidase reaction that is catalyzed by ferrous lipoxygenase. However, the mechanism underlying the conversion of alkoxyl radical into OxoODE remains obscure. In the present study, we confirmed that OxoODEs are produced in the lipoxygenase/linoleate system in an oxygen-dependent manner. Interestingly, we revealed a correlation between the ( E / Z )-OxoODEs content and the ( E / E )-HpODEs content in the system. ( E / E )-HpODEs could have been derived from ( E / E )-linoleate peroxyl radicals, which are generated by the reaction between a free linoleate allyl radical and an oxygen molecule. Notably, the ferrous lipoxygenase-linoleate allyl radical (LOx(Fe 2+ )-L·) complex, which is an intermediate in the lipoxygenase/linoleate system, tends to dissociate into LOx(Fe 2+ ) and a linoleate allyl radical. Subsequently, LOx(Fe 2+ ) converts ( E / Z )-HpODEs to an ( E / Z )-linoleate alkoxyl radical through one-electron reduction. Taken together, we propose that ( E / Z )-OxoODEs and ( E / E )-HpODEs are produced through radical–radical dismutation between ( E / Z )-linoleate alkoxyl radical and ( E / E )-linoleate peroxyl radical. Furthermore, the production of ( E / Z )-OxoODEs and ( E / E )-HpODEs was remarkably inhibited by a hydrophobic radical scavenger, 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO). On the contrary, water-miscible radical scavengers, 4-hydroxyl-2,2,6,6-tetramethylpiperidine 1-oxyl (OH-TEMPO) and 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline- N -oxyl (CmΔP) only modestly or sparingly inhibited the production of ( E / Z )-OxoODEs and ( E / E )-HpODEs. These facts indicate that the radical–radical dismutation between linoleate alkoxyl radical and linoleate peroxyl radical proceeds in the interior of micelles..
