Eicosanoids and Other Bioactive Lipids

Abstract

The eicosanoids are a group of compounds derived from the 20 carbon-containing polyunsaturated fatty acid, arachidonic acid (AA) (Fig. 1). The most abundant members of this group of compounds are the prostaglandins (PGs) and leukotrienes (LTs). Eicosanoids were first recognized in the 1930s as the substance in semen that caused contraction of smooth muscle, hence the name “prostaglandin.” The structures of the compounds were not identified for another 30 yr, and the biosynthetic pathways were described shortly thereafter (1). The critical importance of PG to inflammatory processes became evident in 1971 when Vane and his co-workers discovered that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) worked by inhibiting the production of PG. The mechanism by which this occurs is through inhibition of cyclooxygenase (COX, PGH synthase), the first enzyme in the committed pathway for prostanoid synthesis (2). The understanding that inhibition of PG synthesis was responsible for the anti-inflammatory, antipyretic, and analgesic effects of NSAIDs was accompanied by the recognition that the common side effects of this class of drugs (gastric ulceration, bleeding, and renal dysfunction) were mechanism based; that is, both the therapeutic effects and the side effects of NSAIDs were the result of inhibition of prostanoid biosynthesis. The duality of PGs as mediators of both physiologic and pathologic functions was clarified when two different isoforms of COX, COX-1 and COX-2, were identified using molecular techniques.