Lipid-linked disorders

Lipids in the Assembly of Membrane Proteins and Organization of Protein Supercomplexes Implications for Lipid-Linked Disorders... 

Williams, M.L., and P.M. Elias. 1981. Stratum corneum lipids in disorders of cornification Increased cholesterol sulfate content of stratum corneum in recessive x-linked ichthyosis. J Clin Invest 68 1404. 

Now that the composition of one of the most complex enzymes in nature as well as some of the interactions between subunits have been defined, further work needs to concentrate on a number of issues. These include the specific functions of the various subunits of the complex in the glycosylation process, the regulation of the enzyme and the coupling of OST to lipid-linked oligosaccharide precursor formation, to protein translocation and to protein folding. One may also predict defects in this enzyme that may lead to abnormal glycosylation as it occurs in the so-called carbohydrate deficient glycoprotein syndrome, a severe human disorder with a multisystemic clinical picture [157-160]. 

The stratum corneum consists of denucleated corneocytes filled with cross-linked proteins, while the intercellular space is occupied by lipids synthesized prior to and during cornification [24], Formation of this barrier relies on the cornification of epidermal keratinocytes, which undergo growth arrest, terminal differentiation, and an epidermal-specific cell death, referred to as planned cell death [25], Abnormalities in any of these programmed events may lead to epidermal disorders such as psoriasis, atopic dermatitis, and cancer. Flowever, biological events that enable basal cells (stem cells) to proliferate, differentiate, and commit planned cell death are still poorly understood [10]. The keratinocyte differentiation process can be stimulated by prodifferentiation agents such as extracellular calcium and 1,25-dihydroxy cholecalciferol (referred to as vitamin D3 hereafter) [23], Aberrant or absent differentiation can be found in other skin disorders such as atopic keratosis, seborrheic keratosis, and rosacea. 

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