Reaction participants Show >> << Hide
- Name help_outline N-acyl (9R)-hydroperoxy-(10E,12Z)-octadecadienoate octadecasphing-4E-enine Identifier CHEBI:77889 Charge 0 Formula C37H67NO7R SMILEShelp_outline CCCCCCCCCCCCC\C=C\[C@@H](O)[C@H](CO)NC(=O)[*]OC(=O)CCCCCCC[C@@H](OO)\C=C\C=C/CCCCC 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline N-acyl-(9R,10R)-epoxy-(13R)-hydroxy-(11E)-octadecenoate (4E)-octadecasphin-4-enine Identifier CHEBI:77891 Charge 0 Formula C37H67NO7R SMILEShelp_outline CCCCCCCCCCCCC\C=C\[C@@H](O)[C@H](CO)NC(=O)[*]OC(=O)CCCCCCC[C@H]1O[C@@H]1\C=C\[C@H](O)CCCCC 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:41243 | RHEA:41244 | RHEA:41245 | RHEA:41246 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope.
Zheng Y., Yin H., Boeglin W.E., Elias P.M., Crumrine D., Beier D.R., Brash A.R.
A barrier to water loss is vital to maintaining life on dry land. Formation of the mammalian skin barrier requires both the essential fatty acid linoleate and the two lipoxygenases 12R-lipoxygenase (12R-LOX) and epidermal lipoxygenase-3 (eLOX3), although their roles are poorly understood. Linoleat ... >> More
A barrier to water loss is vital to maintaining life on dry land. Formation of the mammalian skin barrier requires both the essential fatty acid linoleate and the two lipoxygenases 12R-lipoxygenase (12R-LOX) and epidermal lipoxygenase-3 (eLOX3), although their roles are poorly understood. Linoleate occurs in O-linoleoyl-ω-hydroxyceramide, which, after hydrolysis of the linoleate moiety, is covalently attached to protein via the free ω-hydroxyl of the ceramide, forming the corneocyte lipid envelope, a scaffold between lipid and protein that helps seal the barrier. Here we show using HPLC-UV, LC-MS, GC-MS, and (1)H NMR that O-linoleoyl-ω-hydroxyceramide is oxygenated in a regio- and stereospecific fashion by the consecutive actions of 12R-LOX and eLOX3 and that these products occur naturally in pig and mouse epidermis. 12R-LOX forms 9R-hydroperoxy-linoleoyl-ω-hydroxyceramide, further converted by eLOX3 to specific epoxyalcohol (9R,10R-trans-epoxy-11E-13R-hydroxy) and 9-keto-10E,12Z esters of the ceramide; an epoxy-ketone derivative (9R,10R-trans-epoxy-11E-13-keto) is the most prominent oxidized ceramide in mouse skin. These products are absent in 12R-LOX-deficient mice, which crucially display a near total absence of protein-bound ω-hydroxyceramides and of the corneocyte lipid envelope and die shortly after birth from transepidermal water loss. We conclude that oxygenation of O-linoleoyl-ω-hydroxyceramide is required to facilitate the ester hydrolysis and allow bonding of the ω-hydroxyceramide to protein, providing a coherent explanation for the roles of multiple components in epidermal barrier function. Our study uncovers a hitherto unknown biochemical pathway in which the enzymic oxygenation of ceramides is involved in building a crucial structure of the epidermal barrier. << Less
J. Biol. Chem. 286:24046-24056(2011) [PubMed] [EuropePMC]
This publication is cited by 6 other entries.