The molecular biology of mammalian arachidonic acid metabolism

The metabolism of arachidonic acid by cyclooxygenase and lipoxygenase enzymes results in a wide range of oxidized products with potent biological activities. These metabolites, which include the prostaglandins and leukotrienes, have been implicated in the pathogenesis of a variety of inflammatory diseases. Research over the last decade has focused primarily on the elucidation of the chemical structure of the metabolites and their biological effects in vitro and in vivo. Recently, research on the enzymes that produce these bioactive metabolites through oxidization of arachidonic acid has intensified. Recombinant DNA techniques have enabled investigators to determine the nucleotide sequences for several of the enzymes in the arachidonic acid cascade. The resulting cDNAs are now being used to further investigate the biochemical and biological features of arachidonic acid metabolism. The purpose of this paper is to review how the cDNAs for these enzymes were obtained, what information they convey, and how they are being applied in current research.