Eicosanoids: a family of bioactive lipids derived via the oxidation of 20-carbon omega-3 or omega-6 polyunsaturated fatty acids, such as prostaglandins, thromboxanes, and leukotrienes
Cyclic pathway: describes the pathway, initiated by prostaglandin G/H synthase, PGS (also called prostaglandin endoperoxide synthetase), for the synthesis of arachidonic acid-derived eicosanoids containing a cyclic moiety
Linear pathway: describes the pathway, initiated through the action of lipoxygenases (LOXs), for the synthesis of arachidonic acid-derived eicosanoids with linear structure
Cyclooxygenase (COX): common name for prostaglandin G/H synthase which possesses both cyclooxygenase and peroxidase activities, 2 principal COX enzymes exist in humans, COX1 and COX2
Peptidoleukotrienes: also called the cysteinyl leukotrienes, LTC4, LTD4, LTE4, and LTF4 constitute this group of eicosanoids because of the presence of amino acids
Slow-reacting substance of anaphylaxis (SRS-A): consists of the leukotrienes LTC4, LTD4, and LTE4, secreted by mast cells during anaphylactic reaction, induces slow contraction of smooth muscle resulting in bronchoconstriction
Introduction to the Eicosanoids
The principal eicosanoids consist of the prostaglandins (PG), thromboxanes (TX), leukotrienes (LT), and lipoxins (LX). The PG and TX are collectively identified as prostanoids. The nomenclature of the prostanoids includes a subscript number, which refers to the number of carbon-carbon double bonds that exist in the molecule. The majority of the biologically active prostaglandins and thromboxanes are referred to as series-2 molecules due to the presence of 2 double bonds. There are, however, important series-1 and series-3 prostaglandins and thromboxanes. The predominant leukotrienes are series-4 molecules due to the presence of 4 double bonds. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. The lipoxins (see Chapter 24) are anti-inflammatory lipids synthesized through lipoxygenase interactions (hence the derivation of the name).
Overall, the various eicosanoids can be divided into 3 distinct groups dependent upon the source of origin. The series-1 and -3 prostanoids (and related leukotrienes) are derived from dietary intake of linoleic acid and α-linolenic acid (ALA), respectively, whereas the series-3 prostanoids (and series-4 leukotrienes and the lipoxins) are derived from arachidonic acid released from membrane phospholipids (Figure 22-1).
The 3 groups of eicosanoids and their biosynthetic origins. (, cyclooxygenase pathway; , lipoxygenase pathway; LT, leukotriene; LX, lipoxin; PG, prostaglandin; PGI, prostacyclin; TX, thromboxane.) The subscript denotes the total number of double bonds in the molecule and the series to which the compound belongs. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper's Illustrated Biochemistry, 29th ed. New York, NY: McGraw-Hill; 2012.
The eicosanoids produce a wide range of biological effects on inflammatory responses (predominantly those of the joints, skin, and eyes), on ...