Eicosanoids and isoeicosanoids: Indices of cellular function and oxidant stress

Abstract

Arachidonic acid (AA) is an unsaturated fatty acid constituent of the phospholipid domain of cell membranes. It is subject to release via mobilization of phospholipases, particularly a cytoplasmic phospholipase A2. Thereafter, it may be metabolized by at least two cyclooxygenase (COX) isoforms to prostaglandins and related compounds, via lipoxygenases to leukotrienes and via p450-catalyzed metabolism to epoxyeicosatrienoic acids. Collectively, these bioactive lipids are termed eicosanoids. All of these lipids express potent bioactivity in vitro. Clinical studies have already demonstrated the importance of COX and lipoxygenase (LOX) products in human disease. The generation of models of COX, LOX and prostaglandin receptor gene inactivation is likely to broaden our insight into the importance of these compounds in vivo. Crystallization of the biosynthetic enzymes is likely to facilitate the development of highly specific inhibitors, as is the case already for COX-2. AA possesses intrinsic biological properties. It is also subject to free radical attack, generating isomeric eicosanoid species, the isoeicosanoids. These compounds may also express biological activity in vitro, although their importance in vivo is unclear. Development of specific assays for these compounds in urine suggests their utility as noninvasive indices of oxidant stress in vivo.