One electron redox reaction at lower oxygen content is common reaction in plants and mammalian lipoxygenases

Ferrous lipoxygenases seem to be activated through a feedback control mechanism via fatty acid hydroperoxides generated from polyunsaturated fatty acids (PUFAs) by partially existing ferric lipoxygenases. However, during leukotriene synthesis, feedback activation of ferrous 5-lipoxygenase in the presence of arachidonic acid (AA) was not observed. In the present study, we examined the feedback activation of ferrous 5-lipoxygenase in the 5-lipoxygenase/AA system in the presence of linoleic aicd (LA), which is a predominant component of membrane phospholipids. When potato 5-lipoxygenase was incubated with arachidonic acid and linoleic acid in the presence of nitroxyl radical, 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-N-oxyl (Cm∆P), one-electron redox cycle reaction between ferric 5-lipoxygenase and ferrous one was detected. For each revolution of the cycle, one molecule of PUFA and one molecule of its hydroperoxide were converted into PUFA-allyl radical-Cm∆P adduct ([PUFA-H]·-Cm∆P) and PUFA-epoxyallyl radical-Cm∆P adduct ([PUFA-H+O]·-Cm∆P), respectively. The ratios, [AA-H]·-Cm∆P/[LA-H]·-Cm∆P and [AA-H+O]·-Cm∆P/[LA-H+O]·-Cm∆P, were estimated to be 1.7 and 0.13, respectively. These facts indicate that ferrous 5-lipoxygenase is activated through feedback control in the presence of linoleic acid, and that resulting ferric 5-lipoxygenase catalyzes the stoichiometric synthesis of leukotrienes from arachidonic acid. In conclusion, the biosynthesis of leukotrienes is remarkably efficient.