ArticleProceedings of the National Academy of Sciences of the United States of America2003
The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases-Review Article.Frontiers in medicine · 2021Pooled it
- Hepoxilin A(3) facilitates neutrophilic breach of lipoxygenase-expressing airway epithelial barriers.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- Activation and execution of lipoxygenase catalysis.Redox biochemistry and chemistry · 2026Article
- Bacterial lipoxygenases for fatty acid oxyfunctionalization: advances and future directions.Applied microbiology and biotechnology · 2026Review
- Roles of Lipoxygenases in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Transcription Factor VlbZIP14 Inhibits Postharvest Grape Berry Abscission by Directly ActivatingInternational journal of molecular sciences · 2024Article
- Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024Review
- Evaluation of ω-alkynyl-labeled linoleic and arachidonic acids as substrates for recombinant lipoxygenase pathway enzymes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Functional Characterization of Transgenic Mice Overexpressing Human 15-Lipoxygenase-1 (ALOX15) under the Control of the aP2 Promoter.International journal of molecular sciences · 2023Article
- Review
- Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System.Membranes · 2022Review
- KLF5 governs sphingolipid metabolism and barrier function of the skin.Genes & development · 2022Article
- Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility.Cellular and molecular neurobiology · 2022Article
- Plastidic membrane lipids are oxidized by a lipoxygenase inFrontiers in plant science · 2022Article
- Interacting Effects of Sea Louse (Frontiers in immunology · 2022Article
- Molecular mechanism and candidate biomarkers of morphine for analgesia and addiction effects.Annals of translational medicine · 2022Article
- Article
- Stable analogs of 13‑hydroxy-9,10-trans-epoxy-(11E)-octadecenoate (13,9-HEL), an oxidized derivative of linoleic acid implicated in the epidermal skin barrier.Prostaglandins, leukotrienes, and essential fatty acids · 2021Article
- Discovery of a novel ferroptosis inducer-talaroconvolutin A-killing colorectal cancer cells in vitro and in vivo.Cell death & disease · 2020Article
3 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
Abstract
Lipoxygenase (LOX) enzymes form fatty acid hydroperoxides used in membrane remodeling and cell signaling. Mammalian epidermal LOX type 3 (eLOX3) is distinctive in totally lacking this typical oxygenase activity. Surprisingly, genetic evidence has linked mutations in eLOX3 or a colocalizing enzyme, 12R-LOX, to disruption of the normal permeability barrier of the skin [Jobard, F., Lefèvre, C., Karaduman, A., Blanchet-Bardon, C., Emre, S., Weissenbach, J., Ozgüc, M., Lathrop, M., Prud'homme, J. F. & Fischer, J. (2002) Hum. Mol. Genet. 11, 107-113]. Herein we identify a logical link of the biochemistry to the genetics. eLOX3 functions as a hydroperoxide isomerase (epoxyalcohol synthase) by using the product of 12R-LOX as the preferred substrate. 12R-Hydroperoxyeicosatetraenoic acid (12R-HPETE) is converted to 8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid, one of the isomers of hepoxilin A3, and to 12-ketoeicosatetraenoic acid in a 2:1 ratio. Other hydroperoxides, including 8R-HPETE, 12S-HPETE, and 15S-HPETE, as well as the 13S- and 13R-hydroperoxides of linoleic acid are converted less efficiently. Mass spectrometric analysis of the epoxyalcohol formed from [18O]15S-HPETE showed that both hydroperoxy oxygens are retained in the product. We propose that the ferrous form of eLOX3 initiates a redox cycle, unprecedented among LOX in being autocatalytic, in which the hydroperoxy substrate is isomerized to the epoxyalcohol or keto product. Our results provide strong biochemical evidence for a functional linkage of 12R-LOX and eLOX3 and clues into skin biochemistry and the etiology of ichthyosiform diseases in humans.
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