Arachidonate metabolism

Arachidonate metabolism Eicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth muscle contraction and relaxation, and the release of gastric acid. Eicosanoids are synthesized in humans primarily from arachidonate (all-cis 5,8,11,14-eicosatetraenoate) that is released from membrane phospholipids. Once released, arachidonate is acted on by prostaglandin G/H synthases (PTGS, also known as cyclooxygenases (COX)) to form prostaglandins and thromboxanes, by arachidonate lipoxygenases (ALOX) to form leukotrienes, epoxygenases (cytochrome P450s and epoxide hydrolase) to form epoxides such as 15-eicosatetraenoic acids, and omega-hydrolases (cytochrome P450s) to form hydroxyeicosatetraenoates (Buczynski et al. 2009, Vance & Vance 2008).
Levels of free arachidonate in the cell are normally very low so the rate of synthesis of eicosanoids is determined primarily by the activity of phospholipase A2, which mediates phospholipid cleavage to generate free arachidonate. The enzymes involved in arachidonate metabolism are typically constitutively expressed so the subset of these enzymes expressed by a cell determines the range of eicosanoids it can synthesize.
Eicosanoids are unstable, undergoing conversion to inactive forms with half-times under physiological conditions of seconds or minutes. Many of these reactions appear to be spontaneous.