n-3 Fatty Acids and Hydroperoxide Activation of Fatty Acid Oxygenases
The eicosanoids are extremely potent regulators of cellular and tissue function which are derived from the twenty-carbon fatty acid, arachidonate (20:4n-6). There are two large classes of eicosanoids, the prostaglandins and the leukotrienes (Figure 1). The first committed step in the biosynthesis of each class is catalyzed by a fatty acid oxygenase that produces a hydroperoxide product and that requires a hydroperoxide activator. Thus each oxygenase constitutes an amplifier of hydroperoxide concentration within the cell in which it functions. The amplification process may represent an important molecular tactic for intercellular signaling; an explosive increase in the rate of eicosanoid synthesis is probably necessary to overcome the prevailing rapid rate of eicosanoid inactivation found in most cells. However, a continued excessive rate of eicosanoid synthesis is associated with a variety of pathophysiological situations that are often treated with pharmacological agents that can decrease the biosynthetic rate, such as the steroidal and non-steroidal anti-inflammatory drugs. As long as the rate of metabolic inactivation tends to exceed the rate of biosynthesis, the eicosanoids that are formed do not accumulate to a concentration sufficient to interfere with the behavior of the surrounding cells.
KeywordsBaseline Drift Excessive Rate Prostaglandin Biosynthesis Oxygenase Activity Eicosanoid Synthesis
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