Lipooxygenase pathway

Figure 16.24 Major prostaglandin and leukotriene products derived from arachidonic acid via the cyclooxygenase and 5-lipooxygenase pathways. Major enzymes 1, cyclooxygenase 2, hydroperoxidase 1 + 2, prostaglandin endoperoxidase synthetase 3, thromboxane synthetase 4, prostacyclin synthetase 5, 5-lipooxygenase 6, 9-ketoisomerase 7, PGH-PGF2a reductase 8, 11-ketoisomerase 9, PGE reductase 10, PGD reductase. (Reproduced by permission from Nelson NA, Kelly RC, Johnson, RA. Prostaglandins and the arachidonic acid cascade. Chem Eng News August 30-44, 1982.)...

Any reduction in the availability of free AA, by glucocorticoids or other agents, would virtually block all production of products via both the cyclooxygenase and lipooxygenase pathways. 

Another important metabolic pathway for the metabolism of arachidonic acid the 5-lipooxygenase pathway, which leads to a series of compounds callea leukotrienes (LTs). These compounds appear to be essentially, but not exclusively, of a pathophysiologic nature and are formed in various inflammatory cells. 

These three reports suggested a strong anti-inflammatory activity of 1,8-cineole via both the cyclooxygenase and 5-lipooxygenase pathways, and the possibility of a new, well-tolerated treatment of airway inflammation in obstructive airway disease. 

Eicosanoids, also referred to as icosanoids, are so named because of the 20-carbon constituency that identifies this class of oxygenated lipid molecules. A primary synthetic pathway for these molecules involves the phospholipase-mediated cleavage of a membrane phospholipid to produce arachidonic acid [(all-Z)-ik osa-5,8,ll,14-tetraenoic acid]. From this biologically essential intermediate fatty acid, two major subclasses of eicosanoids can be produced 1) leukotrienes, via the action of lipooxygenases, and 2) prostanoids, via the action of cyclooxygenases (COX-1 and COX-2). Examples of chemical structures for a leukotriene (Fig. la) and three types of prostanoids (Fig. Ib-d) underscore their shared arachidonate origin. 

---