In eicosanoid synthesis

Pathways of arachidonate metabolism in eicosanoid synthesis and their inhibitors. HPETE = Hydroperoxyeicosatetraenoic acid HETE = hydroxyeicosatetraenoic acid PG = prostaglandin PGI = prostacyclin TX = thromboxane. Conversions of arachidonic acid by various enzymes can be inhibited by analogues of the natural fatty acid, e g., the acetylenic analogue 5,8,11,14-eicosatetraynoic acid. 

Burstein S (1991) Cannabinoid induced changes in eicosanoid synthesis by mouse peritoneal ceUs. Adv Exp Med Biol 288 107-112... 

As previously discussed (see p. 338), many important eicosanoids are derived from arachidonic acid. Almost all cellular arachidonic acid is stored in cell membranes as esters at C-2 of glycerol in phosphoglycerides. Release of arachidonic acid from membrane, considered to be the rate-limiting step in eicosanoid synthesis (Figure 12D), results from binding an appropriate chemical... 

The first step in eicosanoid synthesis is the release of arachi-donic acid from C-2 of glycerol in membrane phosphoglyc-eride molecules. Cyclooxygenase converts arachidonic acid into PGG2, which is a precursor of the prostaglandins and the thromboxanes. The lipoxygenases convert arachidonic acid to the precursors of the leukotrienes. 

Of the a-linolenic acid ingested some is incorporated into phosphohpids and cholesterol esters, while very Kttle is elongated and eventually converted into prostaglandins most a-linolenic acid probably is used as fuel. Of the EPA and DHA ingested most likely a greater percentage ends in eicosanoid synthesis. Therefore, different polyunsaturated fatty acids of the (o-3 series cannot be considered as similar with respect to their metabolic fate and their effects. In particular results from experiments... 

Besides watet, the diet must provide metaboEc fuels (carbohydrate and fat) fot bodily growth and activity protein fot synthesis of tissue proteins fiber for roughage minerals for specific metabolic functions cettain polyunsamtated fatty acids of the n-3 and n-6 famihes fot eicosanoid synthesis and other functions and vitamins, otganic compounds needed in small amounts for many varied essential functions. 

Nitric oxide and eicosanoid synthesis haem synthesis. The importance of the pentose phosphate pathway reduced glutathione in maintaining red cell integrity. The respiratory burst in phagocytes. Clotting and complement enzyme cascades. Metabolism of lipoproteins. 

Sambo 1988). Nonsesquiterpene lactones in feverfew were also found to inhibit eicosanoid synthesis with high potency (Sumner et al. 1992). 

There are a number of signs and symptoms of essential fatty acid deficiency. They include scaly and thickened skin, alopecia, increased capillary fragility so that bruising readily occurs, poor wound healing, increased susceptibility to infection and growth retardation in infants and children. Some of these symptoms can be explained by deficiency of eicosanoid synthesis and/or failure to complete cell cycles in various tissues (Chapter 20). Consequently, it is important to detect a deficiency before symptoms develop. The principle underlying the method to do this is described ... 

Arachidonate is used as an example of the processes involved in the synthesis of the eicosanoids. The con-... 

Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase [2] and consequently the synthesis of most eicosanoids. This explains their analgesic, antipyretic, and antirheumatic effects. Frequent side effects of NSAIDs also result from inhibition of eicosanoid synthesis. For example, they impair hemostasis because the synthesis of thromboxanes by thrombocytes is inhibited. In the stomach, NSAIDs increase HCl secretion and at the same time inhibit the formation of protective mucus. Long-term NSAID use can therefore damage the gastric mucosa. 

Lipopolysaccharide had no effect on the protein synthesis ([ HJleucine incorporation) of HC cultured alone. A number of studies concluded that this decrease in protein synthesis was not due to a single cytokine, eicosanoid, or oxygen radical (West et al., 1989). Also, the activity could not be transferred in conditioned supernatant for KC stimulated with LPS alone. However, when... 

Corticosteroids block all the known pathways of eicosanoid synthesis, perhaps in part by stimulating the synthesis of several inhibitory proteins collectively called annexins or lipocortins. They inhibit phospholipase A2 activity, probably by interfering with... 

Corticosteroids and cromolyn are also useful in asthma. Corticosteroids inhibit eicosanoid synthesis and thus limit the amounts of eicosanoid mediator available for release. Cromolyn appears to inhibit the release of eicosanoids and other mediators such as histamine and platelet-activating factor from mast cells. 

Cells of the immune system contribute substantially to eicosanoid biosynthesis during an immune reaction. T and lymphocytes are not primary synthetic sources however, they may supply arachidonic acid to monocyte-macrophages for eicosanoid synthesis. In addition, there is evidence for eicosanoid-mediated cell-cell interaction by platelets, erythrocytes, leukocytes, and endothelial cells. 

Prostaglandins Prostaglandins and the other eicosanoids (prostacyclins, thromboxanes and leukotrienes) are derived from arachidonate. These compounds all act as local hormones. Aspirin reduces inflammation by inhibiting prostaglandin synthase, the enzyme that catalyzes the first step in prostaglandin synthesis. 

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