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...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-02-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520428639 |
| _version_ | 1818600998823788544 |
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| author | Ernst H. Oliw |
| author_facet | Ernst H. Oliw |
| author_sort | Ernst H. Oliw |
| collection | DOAJ |
| description | 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, MnIII-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 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, β-fragmentation, and oxygenation under steric control by the protein. |
| first_indexed | 2024-12-16T12:44:24Z |
| format | Article |
| id | doaj.art-8eff20733c17497784127c0bfa87ffc6 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T12:44:24Z |
| publishDate | 2008-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-8eff20733c17497784127c0bfa87ffc62022-12-21T22:31:19ZengElsevierJournal of Lipid Research0022-22752008-02-01492420428Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenaseErnst H. Oliw0Division of Biochemical Pharmacology, Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, SE-751 24 Uppsala, SwedenManganese 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, MnIII-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 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, β-fragmentation, and oxygenation under steric control by the protein.http://www.sciencedirect.com/science/article/pii/S0022227520428639electron transfer1-linoleoyl-lysoglycerophosphatidylcholinemass spectrometrymetalloenzymesperoxyl radicalsR-lipoxygenase |
| spellingShingle | Ernst H. Oliw Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase Journal of Lipid Research electron transfer 1-linoleoyl-lysoglycerophosphatidylcholine mass spectrometry metalloenzymes peroxyl radicals R-lipoxygenase |
| title | Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase |
| title_full | Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase |
| title_fullStr | Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase |
| title_full_unstemmed | Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase |
| title_short | Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase |
| title_sort | factors influencing the rearrangement of bis allylic hydroperoxides by manganese lipoxygenase |
| topic | electron transfer 1-linoleoyl-lysoglycerophosphatidylcholine mass spectrometry metalloenzymes peroxyl radicals R-lipoxygenase |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520428639 |
| work_keys_str_mv | AT ernstholiw factorsinfluencingtherearrangementofbisallylichydroperoxidesbymanganeselipoxygenase |