EICOSANOIDS AND ISOEICOSANOIDS - INDEXES OF CELLULAR FUNCTION AND OXIDANT STRESS

Arachidonic acid (AA) is an unsaturated fatty acid constituent of the phospholipid domain of cell membranes. It is subject to release via mo bilization of phospholipases, particularly a cytoplasmic phospholipase A,. Thereafter, it may be metabolized by at least two cyclooxygenase (COX) isoforms to prostaglandins and related compounds, via lipoxygena ses to leukotrienes and via p450-catalyzed metabolism to epoxyeicosatr ienoic acids. Collectively, these bioactive lipids are termed eicosano ids. All of these lipids express potent bioactivity in vitro, Clinical studies have already demonstrated the importance of COX and lipoxygen ase (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. Crystalliz ation of the biosynthetic enzymes is likely to facilitate the developm ent of highly specific inhibitors, as is the case already for COX-2. A A possesses intrinsic biological properties. It is also subject to fre e radical attack, generating isomeric eicosanoid species, the isoeicos anoids. 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 noninva sive indices of oxidant stress in vivo.