Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

The demonstration of in vivo arachidonic acid epoxidation and w-hydroxylati on established the cytochrome P450 epoxygenase and w/w-1 hydroxylase as for mal metabolic pathways and as members of the arachidonate metabolic cascade . The characterization of the potent biological activities associated with several of the cytochrome P450-derived eicosanoids suggested new and import ant functional roles for these enzymes in cellular, organ, and body physiol ogy, including the control of vascular reactivity and systemic blood pressu res. Past and current advances in cytochrome P450 biochemistry and molecula r biology facilitate the characterization of cytochrome P450 isoforms respo nsible for tissue/organ specific arachidonic acid epoxidation and w/-1 hydr oxylation, and thus, the analysis of cDNA and/or gene specific functional p henotypes, The combined application of physiological, biochemical, molecula r, and genetic approaches is beginning to provide new insights into the phy siological and/or pathophysiological significance of these enzymes, their e ndogenous substrates, and products.