The prostanoids, PGs and TXs, can structurally be considered relatives of prostanoic acid (Figure 1A). They are derived from polyunsaturated fatty acids, most commonly arachidonic acid (Figure 1B), taking the form typified by PGE2 (Figure1C).
Fig1. Prostanoid structures. Prostaglandins D, E, F, and I (prostacyclin) and the thromboxanes are based on that of prostanoic acid, shown in panel A with the numbering of the carbon atoms. B. The prostanoids are derived from 20-carbon polyunsaturated fatty acids. The most abundant of these is arachidonic acid which gives rise to prostanoids of the 2 series. Also shown is eicosatrienoic acid, which can be converted to prostanoids of the 1 series. C. Prostaglandin E2, derived from arachidonic acid, is named for the family of prostanoids into which it falls (prostaglandins, PG), the substituents on the ring portion of its structure (PGE), and the number of bonds in its two side chains (PGE2). Had it been derived from eicosatrienoic acid, it would have a single double bond and would be designated PGE1. D. The ring structures of other biologically important prostanoids are shown, with the double bonds in the side chains, R1 and R2, assumed to be the same as in PGE2. PGF2α designates the stereochemistry of the hydroxyl group at C-9. PGI2 is also referred to as prostacyclin. Also shown are the structures of the thromboxanes (TX), of which TXA2 is the biologically active form.
Most of the prostaglandins have a five-membered ring and the substituents on it determine the subclass, designated by a single letter, such as D, E, or F (Figure 1D). One prostaglandin, PGI2, also known as prostacyclin, has two adjacent rings, one of which contains an oxygen. TXs have a six-membered ring with one or two oxygens associated with it.
The subscripted 2 following the third letter designates the number of double bonds in the two side chains of the molecule and depends on the polyunsaturated fatty acid from which it is derived. Arachidonic acid gives rise to prostanoids of the 2-series whereas dihomo-γ-linoleic acid (Figure 1B), with its three double bonds, is the substrate for prostanoids of the 1-series. 5c,8c,11c,14c,17c-Eicosapentanoic acid, with five double bonds (Figure 2), is converted to molecules with three double bonds in the two side chains. The hydroxyl group at carbon 9 in PGF is in the α con figuration; thus, for this one PG this Greek letter traditionally follows the number.
Fig2. Dietary sources of eicosanoid precursors. Two dietarily essential fatty acids (EFA; green boxes) give rise to the 20-carbon polyunsaturated fatty acids required for the prostanoids (here typified by PGE) of the 1, 2, and 3 (orange boxes) series as well as that of the open chain leukotrienes and lipoxins. The EFAs and the pathways that convert them are referred to as omega 6 or omega 3 depending on the number of the carbon at which the first double bond begins, counting from the terminal methyl group, the omega carbon. The names of the types of enzyme that catalyze these reactions are shown between the two pathways.
Representatives of the open chain eicosanoids, the leukotrienes and lipoxins, are shown in Figure 3. LTs are essentially modified open chain fatty acids that may be conjugated to glutathione or glutathione degradation products. Lipoxins are open chain fatty acids. As with the prostanoids, the third letter denotes the substituents on the carbon atoms and the number is the number of double bonds, indicating the fatty acid from which the molecule was derived.
Fig3. Other eicosanoids. The structures of representative nonprostanoid biologically important derivatives of arachidonic acid are shown.
Humans are quite limited in their ability to produce fatty acids longer than 18 carbons and to intro duce double bonds beyond C-9. An elongase adds two carbons to palmitate (16C) to form stearate (18C) and there are three desaturases to introduce double bonds at the Δ5, Δ6, and Δ9 positions. These enzymes are also able to use the essential fatty acids, linoleic and linolenic acids to generate the 20-carbon polyunsatu rated fatty acids from which the eicosanoids are synthesized, as shown in Figure 2. It is the role of linoleic and linolenic acids in the production of the eicosanoids that renders them essential components of human diets.
