A KERATINOCYTE-SPECIFIC EPOXYGENASE, CYP2B12, METABOLIZES ARACHIDONIC-ACID WITH UNUSUAL SELECTIVITY, PRODUCING A SINGLE MAJOR EPOXYEICOSATRIENOIC ACID

The CYP monooxygenase, CYP2B12, is the first identified skin-specific cytochrome P450 enzyme. It is characterized by high, constitutive expr ession in an extrahepatic tissue, the sebaceous glands of cutaneous ti ssues. It is expressed exclusively in a subset of differentiated kerat inocytes called sebocytes, as demonstrated by Northern blot analysis, in situ hybridization, and polymerase chain reaction. The onset of its expression coincides with the morphological appearance of sebaceous g lands in the neonatal rat. Recombinant CYP2B12 produced in Escherichia coli epoxidizes arachidonic acid to 11,12- and 8,9-epoxyeicosatrienoi c acids (80 and 20% of total metabolites, respectively). The identific ation of arachidonic acid as a substrate for this skin-specific CYP mo nooxygenase suggests an endogenous function in keratinocytes in the ge neration of bioactive lipids and intracellular signaling.