Structures of stratum corneum and formation of the corneocyte lipid envelope (CLE).

(a) An image of the cornified barrier obtained by electron microscopy [5]. In stratum corneum, the corneocytes are bound together by the fusion of three substructures: (i) polymerized proteins forming the corneocyte envelope (CE), (ii) extracellular lamellar lipids between cells, and (iii) a monolayer of covalently bound ceramides and fatty acids, the corneocyte lipid envelope (CLE), covering the CE and forming a scaffold for the extracellular lamellar lipids. (b) Our working hypothesis [9] requires the LOX-catalyzed oxidation of the linoleate in esterified omega-hydroxyacyl-sphingosine (EOS), ceramide, facilitating hydrolysis of the ester bond, separating ceramide OS for coupling to the CE protein by transglutaminase, finally forming the CLE. Trihydroxy-linoleic acid (triol) cleaved from ceramide EOS is produced as the final metabolite. (i) 9-hydroperoxy-11,12-octadecadienoate, (ii) 9,10-epoxy-11E-13-hydroxyoctadecenoate (iii) 9,10,13-trihydroxy-11E-octadecenoate.