Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase
2008 (English)In: Journal of Lipid Research, ISSN 0022-2275, Vol. 49, no 2, 420-428 p.Article in journal (Refereed) Published
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(pD7.5), and aqueous Fe3+ did not transfer 11S-hydroperoxy-9Z,12Z,15Z-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, beta-fragmentation, and oxygenation under steric control by the protein.
Place, publisher, year, edition, pages
2008. Vol. 49, no 2, 420-428 p.
electron transfer, 1-linoleoyl-lysoglycerophosphatidylcholine, mass spectrometry, metalloenzymes, peroxyl radicals, R-lipoxygenase, solvent deuterium isotope effect, site-directed mutagenesis
IdentifiersURN: urn:nbn:se:uu:diva-15063DOI: 10.1194/jlr.M700514-JLR200ISI: 000252433200017OAI: oai:DiVA.org:uu-15063DiVA: diva2:42834