The following excerpts were taken from Modern nutrition in health and disease (Tenth Edition), edited by Shils et al. It's a very impressive tome with some powerhouse contributors. I hope to discuss eicosanoids again sometime, but for now, here's a brief discussion. I refer you to the book itself (a thick and hefty reference!) for more details.

Prostaglandins, prostacyclins, thromboxanes, and leuko-trienes are all 20-carbon molecules known collectively as eicosanoids, a term of Greek etymology meaning 20. The synthetic pathways for several important eicosanoids are shown in Figure 42.9. The first step involves liberating arachidonic acid from membrane phospholipids through a reaction catalyzed by cytosolic phospholipase A2, an enzyme expressed in practically all cells. Its enzymatic activity is upregulated via phosphorylation triggered by mechanical stresses, by increases in cytosolic calcium ion concentrations, or by cytokines including IL-lp and TNF-a. In addition, transcription of phospholipase A2 is increased by IL-lp and TNF-a and is inhib¬ited by glucocorticoids. Once liberated, arachidonic add can be processed along the COX or the lipoxygenase pathway (or metabolized in other ways outside the scope of this chapter).


Like cytokines, the eicosanoids were targets of clinical intervention long before their molecular characteristics were understood (45). Through the centuries, myrtle leaves, poplar extracts, and willow tree bark have been used to relieve pain and fever. By the nineteenth century, the active substances in these botanicals—salicylates—were isolated, and synthetic forms were produced. Notably. acetylsalicylic acid or aspirin (a, acetyl; spirin, from Spi¬raea, the genus of natural sources of salicylates) came on the market in 1899. Aspirin and other nonsteroidal antiin-flammatory drugs (NSAIDs) inhibit synthesis of many eicosanoids, but this concept would not be understood for another 70 years.

In the early 1930s, semen was found to contain lipids that relaxed isolated uterine smooth muscle in vitro and increased blood pressure when it was injected intravenously into animals. The term "prostaglandin" arose from the assumption that the prostate gland was the source of these lipids. Ensuing discoveries revealed that the term prostaglan¬din was too restrictive, because these lipids were actually produced by a wide variety of tissues throughout the body (reminiscent of the problems with cytokine nomencla¬ture). At about the same time, other bioactive lipids were isolated, including slow-reacting substance (SRS), which caused a delayed, sustained contraction of isolated smooth muscle (in contrast to the immediate, transient effect of histamine), and rabbit aorta-contracting substance (RCS).

In the 1970s, the biosynthetic pathway for prostaglandins was elucidated, including the isolation of a key enzyme in this process, cyclooxygenase (COX). This led to the discovery that aspirin-like drugs blocked the enzymatic activity of COX (45). During this same period, other products of COX, including thromboxanes (the major bioactive com¬ponents of RCS) and prostacyclins, were characterized. Furthermore, the COX-m dependent synthesis pathways for leukotrienes (the bioactive components of SRS) were characterized.


Other interests:
Technical writing | ELISPOT | reference samples