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The eicosanoids are an important group of endogenous fatty acid autacoids that are synthesized from arachidonic acid, a 20-carbon fatty acid lipid in cell membranes. Families of eicosanoids of clinical importance include straight-chain derivatives (leukotrienes) and cyclic derivatives (prostacyclin, prostaglandins, and thromboxane).
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The principal eicosanoids are derived from arachidonic acid. The major subgroups are the leukotrienes and a group of cyclic molecules, including prostaglandins, prostacyclin, and thromboxane. The leukotrienes retain the straight-chain configuration of the parent arachidonic acid. Prostacyclin, thromboxane, and other members of the prostaglandin group are cyclized derivatives of arachidonic acid. There are several series for most of the principal subgroups, based on different substituents (indicated by letters A, B, etc) and different numbers of double bonds (indicated by a subscript number) in the molecule.
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Active eicosanoids are synthesized in response to a wide variety of stimuli (eg, physical injury, immune reactions). These stimuli activate phospholipases in the cell membrane or cytoplasm, and arachidonic acid (a tetraenoic [4 double bonds] fatty acid) is released from membrane phospholipids (Figure 18–1). Arachidonic acid is then metabolized by several different enzymes. The two most important are lipoxygenase (LOX), which results in straight-chain leukotrienes, and cyclooxygenase (COX), which results in cyclization to prostacyclin, prostaglandins, or thromboxane. COX exists in at least two forms. COX-1 is found in many tissues; the prostaglandins produced by COX-1 appear to be important for a variety of normal physiologic processes (see later discussion). In contrast, COX-2 is found primarily in inflammatory cells; the products of its actions play a major role in tissue injury (eg, inflammation). In addition to these inflammatory functions, COX-2 is also responsible for synthesis of prostacyclin and of prostaglandins important in normal renal function. Thromboxane is preferentially synthesized in platelets, whereas prostacyclin is synthesized in the endothelial cells of blood vessels. Naturally occurring eicosanoids have very short half-lives (seconds to minutes) and are inactive when given orally.
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