d inhibition of production of proinflammatory cytokines, which may be relevant to their involvement in lupus and other rheumatological conditions. -Linolenic acid Insulin Glucose Dihomo-GLA 1 series of prostaglandins Desaturase 5 Arachidonic acid Eicosapentaenoic acid COX-1 and COX-2 Pyruvate Docosahexaenoic acid Prostaglandins of 2 series PGA2, PGE2, PGF2, PGI2 TXA2, LTB4, HETEs, EETs Prostaglandins of 3 series PGA3, PGE3, PGF3, PGI3 TXA3, LTB5 Resolvins Lipoxins Protectins Maresins Cis-linoleic acid and -linolenic acid are essential nutrients because they cannot be synthesized by the human body and are hence called `essential fatty acids’. LA is converted to -linolenic acid by the action of the enzyme 6 desaturase, and GLA is elongated to form dihomo-GLA, the precursor of the 1 series of prostaglandins. 6 desaturase is the rate-limiting step in the metabolism of EFAs. DGLA can also be converted to arachidonic acid by the action of the enzyme 5 desaturase. AA forms the precursor of two series of prostaglandins, 
thromboxanes, and the four series of leukotrienes. ALA is converted to eicosapentaenoic acid by 6 and 5 desaturases. EPA forms the precursor of the three series of prostaglandins and the five series of LTs. EPA can be elongated to form docosahexaenoic acid. AA, EPA, and DHA also form precursors to a group of novel compounds such as LXs, resolvins, protectins, and maresins29 that exhibit anti-inflammatory action. Eicosanoids bind to G-protein-coupled receptors on many cell types and mediate virtually every step of inflammation. They are found in inflammatory exudates, and their synthesis is increased at sites of inflammation. Nonsteroidal anti-inflammatory drugs such as aspirin inhibit cyclooxygenase activity and are thus believed to bring about their anti-inflammatory action, though this has been disputed. On the basis of the involvement of eicosanoids in inflammation, COX-2 inhibitors have been developed. However, recent studies showed that COX-2 inhibitors enhance cardiovascular Journal of Inflammation Research 2010:3 Metabolism of essential fatty acids events,6,10 suggesting that there is a close interaction between eicosanoids and cardiovascular system. Lipoxins, resolvins, protectins, and maresins There are two COX enzymes: the constitutively expressed COX-1 and the inducible enzyme COX-2. order Elesclomol different types of PGs are formed by the action of COX enzymes depending on the substrate fatty acid from which they are derived. Different types of PGs exhibit different actions and sometimes diametrically opposite actions. For example, PGE2, PGF2, thromboxane A2, and LTs exhibit proinflammatory actions, whereas PGE1 and prostacyclin show anti-inflammatory actions. Furthermore, the distributions of COX-1 and COX-2 enzymes have restricted tissue distribution. Platelets contain thromboxane synthetase, and hence TXA2, a potent platelet aggregator and vasoconstrictor, is formed in these cells, whereas vascular endothelial cells possess PGI2 synthetase but lack thromboxane synthetase and thus they mainly form, PGI2, a potent platelet antiaggregator and vasodilator. The balance between TXA2 and PGI2 is important in thrombus formation Dovepress 145 Das Dovepress in coronary and cerebral blood vessels. PGE2 is hyperalgesic, causes a marked increase in pain produced by intradermal injection of suboptimal concentrations of histamine and bradykinin, and is involved in cytokine-induced fever during infections. PGD2, PGE2, and PGF2, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19836835 major metabolites
