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标题：Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase
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作者：Ernst H. Oliw
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：2
页码：420-428
DOI：10.1194/jlr.M700514-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Manganese lipoxygenase (Mn-LOX) catalyzes the rearrangement of bis -allylic S -hydroperoxides to allylic R -hydroperoxides, but little is known about the reaction mechanism. 1-Linoleoyl-lysoglycerophosphatidylcholine was oxidized in analogy with 18:2n-6 at the bis -allylic carbon with rearrangement to C-13 at the end of lipoxygenation, suggesting a “tail-first” model. The rearrangement of bis -allylic hydroperoxides was influenced by double bond configuration and the chain length of fatty acids. The Gly316Ala mutant changed the position of lipoxygenation toward the carboxyl group of 20:2n-6 and 20:3n-3 and prevented the bis -allylic hydroperoxide of 20:3n-3 but not 20:2n-6 to interact with the catalytic metal. The oxidized form, Mn^III-LOX, likely accepts an electron from the bis -allylic hydroperoxide anion with the formation of the peroxyl radical, but rearrangement of 11-hydroperoxyoctadecatrienoic acid by Mn-LOX was not reduced in D₂O (pD 7.5), and aqueous Fe³⁺ did not transfer 11 S -hydroperoxy-9 Z ,12 Z ,15 Z -octadecatrienoic acid to allylic hydroperoxides. Mutants in the vicinity of the catalytic metal, Asn466Leu and Ser469Ala, had little influence on bis -allylic hydroperoxide rearrangement. In conclusion, Mn-LOX transforms bis -allylic hydroperoxides to allylic by a reaction likely based on the positioning of the hydroperoxide close to Mn³⁺ and electron transfer to the metal, with the formation of a bis -allylic peroxyl radical, β-fragmentation, and oxygenation under steric control by the protein.