Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase.
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 D(2)O (pD 7.5), and aqueous Fe(3+) 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 Mn(3+) 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.
Oliw
Ernst H
EH
Division of Biochemical Pharmacology, Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden. ernst.oliw@farmbio.uu.se
D000818:Animals; D002384:Catalysis; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008041:Linoleic Acids / Q000737:chemistry / Q000378:metabolism; D008084:Lipoxygenase / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism
D008041:Linoleic Acids; D010545:Peroxides; D010713:Phosphatidylcholines; C049375:perhydroxyl radical; D006861:Hydrogen Peroxide; C112608:manganese lipoxygenase; D008084:Lipoxygenase