THE NATURE OF THE EPIDERMAL BARRIER - BIOCHEMICAL ASPECTS

As epidermal keratinocytes differentiate, they synthesize lipids, much of which are packaged into small organelles called lamellar granules, Acetate from the circulation serves as the principal carbon source fo r epidermal lipid synthesis, and the required energy is produced prima rily by glycolysis with reduction of the resulting pyruvate to lactate . Late in the differentiation program, the contents of the lamellar gr anules are extruded into the extracellular spaces, Lipases, also deliv ered to the intercellular spaces via the lamellar granules, completely break down the remaining phospholipids and deglycosylate the glycolip ids. Ceramides, cholesterol and fatty acids remain as the principal li pids in the stratum corneum. The modification of the lipid initially e xtruded from the lamellar granules is accompanied by a transformation from small, flattened vesicles to broad multilamellar lipid sheets whi ch fill most of the intercellular spaces of the stratum corneum, and i t is this intercellular lipid that provides the epidermal permeability barrier, Knowledge of the molecular events underlying formation and f unction of the permeability barrier can both improve our understanding of the normal protective role of the barrier and could be useful in d esign of transdermal drug delivery systems.