ABSTRACT
The importance of extracellular lipids for mammalian epidermal barrier function is well established. The specific roles in epidermal function for the predominant lipid species by weight, ceramides (Cer), have been revealed in studies in both normal and diseased humans, as well as in animal models and in model membranes in vitro. Specifically, contents of these lipids are altered in patients with both atopic dermatitis (AD) (1,2) and psoriasis (3,4). Likewise, cholesterol (Chol), as well as essential and non-essential free fatty acids (FFAs) play separate, critical roles in barrier homeostasis. As all three of the major stratum corneum lipid classes, Chol, Cer, and FFAs derive from their respective precursor lipids, the enzymatic pathways responsible for producing these lipid end-products have garnered much recent attention. This chapter will review these critical enzymatic steps in the generation of epidermal barrier lipids, including details regarding their regulation, as well as their association with cutaneous disease states. Given that the human stratum corneum (SC) contains at least nine major Cer fractions, many of which are unique to the epidermis, including omega(o)-hydroxylated and o-acylated forms, as well as covalently attached Cer species, special emphasis is accorded herein to this unique class of lipids. Finally, where appropriate, the role of these lipids and/or their precursors in epidermal proliferation, differentiation, and/or apoptosis, will also be discussed.
