ABSTRACT
Role in Epidermal Hyperproliferation: Generation of 13SHydroxyoctadecadienoic Acid (13S-HODE) by 15-LOX. Although the feeding of LA to EFAD animals reverses the major cutaneous symptoms of EFA deficiency, which include hyperproliferation and increased transepidermal water loss), the mechanism for such a reversal is not known. Thus after the first recognition that skin enzyme preparations cannot biosynthesize AA (7), we explored the possibility that accumulating cutaneous LA may undergo oxidative metabolism, presumably via the LOX pathway, generating bioactive products that in turn attenuate the skin hyperproliferative activity. To test this hypothesis, we incubated in vitro LA with soybean 15-LOX or 15-LOX prepared from skin epidermis. The major metabolite identified in these incubations was 13S-HODE and a minor metabolite was 9-HODE. The skin epidermis is unique in that it preferentially metabolizes LA to 13S-HODE with a negligible amount transformed to γ-linolenic acid (GLA, 18:3n-6), suggesting that 13S-HODE may play a role in vivo. Similarly, the feeding of corn oil to normal guinea pigs led to enhanced amounts of 13S-HODE in the epidermis. A schematic illustration of the metabolism of dietary LA in the epidermis is shown in Figure 1.
