Abstract
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.
Highlights
Manganese lipoxygenase (Mn-LOX) catalyzes the rearrangement of bis-allylic S-hydroperoxides to allylic Rhydroperoxides, 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
During the rapid linear phase of biosynthesis of UV light-absorbing products at 237 nm (13-hydroperoxyoctadecatrienoic acid (HPOTrE), traces of 9-HPOTrE), the apparent amounts of the two main products were estimated by LC-MS/MS analysis. 11-HPOTrE averaged 25%, and 13-HPOTrE averaged ?75%
The first linear increase in UV absorbance was followed by a second linear phase, during which 11-HPOTrE was converted to 13-HPOTrE [15]
Summary
Manganese lipoxygenase (Mn-LOX) catalyzes the rearrangement of bis-allylic S-hydroperoxides to allylic Rhydroperoxides, 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. Autoxidation of polyunsaturated fatty acids occurs by the abstraction of hydrogen at bis-allylic carbons, with the formation of peroxyl radicals, yet lipoxygenation and autoxidation differ in other respects. Homolytic cleavage by Mn-LOX is influenced by the position of the hydroperoxide at the active site, as judged from the effects of substrate chain length and double bond configuration [25].
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