Polyunsaturated fatty acids eicosanoids from

Fig. 2. Biosynthetic pathways of polyunsaturated fatty acid and eicosanoid synthesis. The terminology used indicates first the number of carbons in the acyl chain, then the number of double bonds, and then the number of carbons from the methyl terminus at which the most distal double bond is located (e.g., 20 4n-3). HPETEs hydroperoxyeicosatetraenoic acids HETEs hydroxyeicosa-tetraenoic acids.

Eicosanoids are ceU-regulating polyunsaturated fatty acids primarily synthesized from arachidonic acid and released by the action of phospholipase A2 from lipids in ceU membranes. 

The available evidence suggests that n-6 fatty acid-derived eicosanoids are generally proinflamma-tory and prothrombotic. In contrast, eicosanoids derived from n-3 fatty acids have attenuated biological activity on cardiovascular risk factors. The effects of altering n-6 PUFA intake, in conjvmction with changes in other polyunsaturated fatty acids, as well as other classes of fatty acids, on endothelial function, thrombosis, and inflammation are not understood. The relative proportion of all the classes of fatty acids in the diet may well be more important and relevant to cardiovascular risk reduction than any single class of fatty acids. Clearly such research warrants further investigation. 

Eicosanoids are formed from 20-carbon polyunsaturated fatty acids and make up an important group of physiologically and pharmacologically active compounds known as prostaglandins, thromboxanes, leukotrienes, and lipoxins. 

EICOSANOIDS ARE FORMED FROM C20 POLYUNSATURATED FATTY ACIDS... 

Nitric oxide and peroxynitrite contribute to oxidative damage 569 Production of eicosanoids from polyunsaturated fatty acids such as arachidonic acid may generate reactive oxygen species 570 Brain antioxidant defenses modify ischemia-reperfusion injury 570 Reactive oxygen species may modify both the excitotoxic and the apoptotic components of ischemic brain damage 570... 

Fatty acid derivatives include a large and diverse group of compounds named eicosanoids, which includes thromboxanes, prostaglandins and leukotrienes, all of which are biochemically derived from arachidonic acid (a long-chain polyunsaturated fatty acid). 

Cyciooxygenase (COX) PGH synthase the first enzyme in the generation of the eicosanoids from polyunsaturated fatty acids. 

Chronic changes in the type of fat in the diet can change the type of polyunsaturated fatty acids in the phospholipids that are components of membranes and hence change fluidity of the membrane. This might change the activity of the phospholipase and/or the type of eicosanoid produced from... 

A summary of the processes for producing the eicosanoids from the polyunsaturated fatty acid, arachidonic acid, is presented in Figure 11.27. The two enzymes separate for synthesising the prostanoids or the leucotrienes are cyclooxygenase and lipoxygenase, respectively. Whether prostanoids or leucotrienes are produced in any given tissue will depend on the relative activities of these two enzymes in that tissue. 

All eicosanoids are derived from arachidonic acid (20 4(A5 8,11 14)) (Fig. 10-18), the 20-carbon polyunsaturated fatty acid from which they take their gen-... 

Eicosanoids Are Formed from 20-Carbon Polyunsaturated Fatty Acids... 

Eicosanoids The eicosanoid hormones (prostaglandins, thromboxanes, and leukotrienes) are derived from the 20-carbon polyunsaturated fatty acid arachidonate. 

The simplest class of lipids are FAs. This group includes various types of fatty acids, eicosanoids, fatty alcohols, fatty aldehydes, fatty esters, fatty amides, fatty nitriles, fatty ethers, and hydrocarbons. Many FAs, especially the eicosanoids derived from n-6 and n-3 polyunsaturated fatty acids, have... 

Recently Liu and Weller [84] have reviewed the arachidonic acid metabolism in filarial parasites and other helminths. Arachidonic acid (AA) is a 20 carbon polyunsaturated fatty acid derived from dietary fatty acids. In human tissues, AA is usually present in the esterified form such as glycerolipids, phospholipids and neutral lipids. The free AA, released by phospholipases, undergoes various enzymatic oxygenations to form local mediators such as prostaglandins and leukotrienes, which are collectively known as eicosanoids (Chart 9). These eicosanoids are associated with platelet aggregation, vasodilation, leukocyte inflammatory and immune functions and cellular adhesion [85]. 

Arachidonate, an essential precursor of prostaglandins and other signal molecules, is derived from linoleate. This 20 4 polyunsaturated fatty acid is the precursor of several classes of signal molecules— prostaglandins, prostacyclins, thromboxanes, and leukotrienes— that act as messengers and local hormones because of their transience. They are called eicosanoids because they contain 20 carbon atoms. Aspirin (acetylsalicylate), an anti-inflammatory and antithrombotic drug, irreversibly blocks the synthesis of these eicosanoids. 

Eicosanoids Oxygenated lipid signaling molecules containing 20 carbons derived from polyunsaturated fatty acids released from membrane phospholipids by the action of phospholipase A. These include the prostanoids produced by the cyclooxygenase pathway and the leukotrienes produced by the lipoxygenase pathway. 

The eicosanoids are locally active hormones (autocoids) that are derived from precursor polyunsaturated fatty acids. The rate-limiting step in the synthesis of eicosanoids is the phospholipase-regulated release of arachidonic add from membranes. Arachi-donic acid metabolism may follow one of three possible pathways. In the first, the cydooxygenase- peroxidase pathway leads to the formation of the prostenoids - prostaglandins and thromboxanes. In the second, the lipoxygenase pathway yields the leuko-trienes and lipoxins. A third pathway, the cytochrome P-450 mono oxygenase pathway is also involved in the metabolism of arachidonic add. 

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