Feedback activation of ferrous 5-lipoxygenase during leukotriene synthesis by coexisting linoleic acid.
Ferrous lipoxygenases seem to be activated through a feedback control mechanism via FA hydroperoxides generated from 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 AA and LA in the presence of nitroxyl radical, 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-N-oxyl (CmDeltaP), one-electron redox cycle reaction between ferric and ferrous 5-lipoxygenase was detected. For each revolution of the cycle, one molecule of PUFA and one molecule of its hydroperoxide were converted into PUFA-allyl radical-CmDeltaP adduct ([PUFA-H].-CmDeltaP) and PUFA-epoxyallyl radical-CmDeltaP adduct ([PUFA-H+O].-CmDeltaP), respectively. The ratios, [AA-H].-CmDeltaP/[LA-H].-CmDeltaP and [AA-H+O].-CmDeltaP/[LA-H+O].-CmDeltaP, 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 LA, and that resulting ferric 5-lipoxygenase catalyzes the stoichiometric synthesis of leukotrienes from AA. In conclusion, the biosynthesis of leukotrienes is remarkably efficient.
Takajo
Tokuko
T
Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kita-Adachi-gun, Saitama 362-0806, Japan.
Tsuchida
Kazunori
K
Ueno
Koichi
K
Koshiishi
Ichiro
I
D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015289:Leukotrienes / Q000737:chemistry* / Q000378:metabolism; D019787:Linoleic Acid / Q000737:chemistry* / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D008956:Models, Chemical; D009589:Nitrogen Oxides / Q000737:chemistry
D015289:Leukotrienes; D009589:Nitrogen Oxides; D016718:Arachidonic Acid; D019787:Linoleic Acid; D008084:Lipoxygenase; C039900:nitroxyl