Metabolism and function of skin lipids.

It is apparent from this review that the skin is an organ displaying a highly active metabolism of PUFA's. It possesses the capacity to biosynthesize, metabolize and interconvert a variety of lipids as outlined in the review. Its inability to desaturate the essential fatty acids underscores the significance of these PUFAs in cutaneous biology. For instance, increases in the concentrations of 20:4n6 as well as certain autacoids are associated with many inflammatory-hyperproliferative dermatoses. However, the origin of 20:4n6, which is found complexed to skin phospholipids, has until recently remained a mystery. Studies undertaken in our laboratory designed to delineate the origin of epidermal 20:4n6, and to elucidate the effects of EFA deficiency and crossover replenishment with dietary oils on epidermal lipid metabolism have demonstrated: (i) that microsomal preparations from rat and guinea pig epidermis lack the capacity to transform 18:2n6 into 18:3n6 (catalyzed by the enzyme delta 6 desaturase) and 20:3n6 into 20:4n6 (catalyzed by the enzyme delta 5 desaturase). This observation implies that 20:4n6, a component of epidermal phospholipids, is biosynthesized elsewhere endogenously and transported to the epidermis for esterification into the phospholipids. In an extension of this work, epidermal microsomal preparations from normal human and diseased human epidermis (clinically uninvolved and involved psoriatic epidermis) were examined in order to determine the activities of the delta 6 and the delta 5 desaturases as well as the elongase, respectively. Our data revealed that normal, uninvolved and involved human epidermal preparations lack the capacity to desaturate 18:2n6 to 18:3n6 and 20:3n6 to 20:4n6. These results are interesting in view of the fact that 20:4n6 metabolites participate in the phlogistic and hyperproliferative processes in psoriasis. It is likely that the increases in the 20:4n6-derived eicosanoids, which are prominent in uninvolved and involved psoriatic skin, are the result of an enhanced epidermal phospholipase A2 activity. The heightened lipase activity would lead to an elevated concentration of free 20:4n6 which, in turn, would result in the reported increase of epidermal eicosanoid levels. (ii) Incubation of 18:3n6 with microsomal preparations from skin specimens from normal, uninvolved and involved psoriatic epidermis revealed the presence of elongase activity capable of converting 18:3n6 into 20:3n6. This activity was markedly elevated (5-fold) in involved hyperproliferative psoriatic preparations.(ABSTRACT TRUNCATED AT 250 WORDS)