Distinguishing levuglandins produced through the cyclooxygenase and isoprostane pathways.
The cyclooxygenase (COX) pathway generates enantiomerically pure levuglandin (LG) E(2) by a rearrangement of the prostaglandin (PG) endoperoxide PGH(2). The isoprostane pathway generates racemic LGE(2) together with stereoisomers, designated collectively as isoLGE(2), through free radical-induced lipid oxidation. Within seconds, both LGs and isoLGs are rapidly sequestered by protein adduction. In theory, the diastereomeric purity of LGE(2)-protein adduct-derived lysyl lactams can reveal the relative contributions of the COX and isoprostane pathways to LGE(2) stereoisomer production in vivo. Notably, however, the detection of LGE(2)-protein adducts does not provide a basis for inferring their formation through the isoprostane pathway in vivo unless the COX pathway can be rigorously excluded. In contrast, LGE(2)structural isomers, designated collectively as iso[n]LGE(2)s, are produced exclusively through the isoprostane pathway. Immunoassays that selectively recognize iso[n]LGE(2)-protein adducts are the only tools available to unambiguously detect and quantify the production of isolevuglandins in vivo through free radical-induced oxidation of arachidonates.
Salomon
Robert G
RG
Department of Chemistry, Case Western Reserve University, 2074, Adelbert Road, Cleveland, OH 44106-7078, USA. rgs@case.edu
D002853:Chromatography, Liquid; D028421:Isoprostanes / Q000378:metabolism*; D013058:Mass Spectrometry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology
D028421:Isoprostanes; D011458:Prostaglandins E; C047684:levuglandin E2; D011451:Prostaglandin-Endoperoxide Synthases