Vitamin E modulates the lipoxygenation of arachidonic acid in leukocytes.
The arachidonic acid released from cellular phospholipids of specifically stimulated platelets and leukocytes is oxygenated enzymatically by two major pathways. A complex cycloxygenase converts some of the free arachidonic acid to labile endoperoxides that are transformed to prostaglandins, thromboxanes and prostacyclin (PGI2). Lipoxygenases convert part of the arachidonic acid to unstable hydroperoxy-eicosatetraenoic acids (OOHETEs) that are transformed to monohydroxyeicosatetraenoic acids (HETEs), oligohydroxy-eicosatetraenoic or -eicostatrienoic acids such as di-HETEs and tri-HETEs, and, in some instances, more complex humoral mediators, including slow-reacting substances. Both the nature of the HETEs and the ratio of the HETEs to the cyclo-oxygenase products are specific characteristics of each type of cell. In human neutrophils, the sum of the lipoxygenase products 5-HETE, 11-HETE and 5,12-di-HETE substantially exceeds the total amount of PGE2 and other cyclo-oxygenase metabolites that are generated concurrently, and the endogenous lipoxygenase products regulate neutrophil function. The present data indicate that vitamin E (alpha-tocopherol) bidirectionally modulates the activity of the lipoxygenase pathway of human neutrophils in vitro. Normal plasma concentrations of alpha-tocopherol enhance the lipoxygenation of arachidonic acid, whereas higher concentrations of alpha-tocopherol exert a suppressive effect that is consistent with its role as a hydroperoxide scavenger.
D001095:Arachidonic Acids / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
D001095:Arachidonic Acids; D003182:Complement C5; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D014810:Vitamin E; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C027356:11-hydroxy-5,8,12,14-eicosatetraenoic acid; D008084:Lipoxygenase