Lipoxins pathway

Figure 23-5. The three groups of eicosanoids and their biosynthetic origins. (PG, prostaglandin PGI, prostacyclin TX, thromboxane LT, leukotriene LX, lipoxin , cyclooxygenase pathway , lipoxygenase pathway.) The subscript denotes the total number of double bonds in the molecule and the series to which the compound...

Figure 23-7. Conversion of arachidonicacid to leukotrienesand lipoxins of series 4 via the lipoxygenase pathway. Some similar conversions occur in series 3 and 5 leukotrienes. (HPETE, hydroperoxyeicosatetraenoate HETE, hydroxyeicosatetraenoate , peroxidase (2), leukotriene A4 epoxide hydrolase , glutathione S-transferase ...

Figure 21-8 The 5-lipoxygenase pathway for biosynthesis of the hydroperoxy- and hydroxy-eicosanoic acids, leukotrienes, and lipoxins.

The EFA stored in the phospholipids of cell membranes are released by phospholipases, and then undergo oxidative transformation by the cyclooxygenase (COX) pathway to prostanoids and by the lipoxygenase pathway to hydroxy fatty acids and leukotrienes. The metabolism to prostanoids is catalyzed by two isoenzymes of COX, a constitutive (COX-1) and an inducible form (COX-2). The main products of COX metabolism of AA are prostaglandin E2 (PGE2), PGI A, and PGD2. In addition, A A is converted via 15-lipoxygenase to 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins, by... 

Lipoxygenase pathway Alternatively, several lipoxygenases can act on arachidonic acid to form 5-HPETE, 12-HPETE and 15-HPETE, which are unstable peroxidated derivatives that are converted to the corresponding hydroxylated derivatives (the HETES), or to leukotrienes or lipoxins, depending on the tissue (Figure 39.3).2... 

Mechanisms of lipoxin action receptors and signalling pathways... 

Romano M, Maddox JF, Serhan CN (1996) Activation of human monocytes and the acute monocytic leukemia cell Une (THP-1) by lipoxins involves unique signaling pathways for Upoxin A4 versus Upoxin B4 evidence for differential Ca2-l- mobilization. J Immunol 157 2149-2154... 

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. 

Three major pathways for the metabolism of arachidonic acid occur in various tissues (Fig. 35.3). The first of these, the cyclooxygenase pathway, leads to the synthesis of prostaglandins and thromboxanes. The second, the lipoxygenase pathway, yields the leukotrienes, HETEs, and lipoxins. The third pathway, catalyzed by the cytochrome P450 system, is responsible for the synthesis of the epoxides, HETEs, and diHETEs. 

B. Lipoxygenase Pathway Synthesis of the Leukotrienes, HETE, and Lipoxins... 

The lipoxygenase pathway (Fig. 21-8) leading to the leukotrienes, lipoxins, and other products is especially active in leukocytes and in mast cells. ... 

Tomhamre S, Gigou A, Edenius C, Lellouche JP, Lindgren JA Conversion of 5,6-dihydroxye-icosatetraenoic acids. A novel pathway for lipoxin formation by human platelets. FEBS I ett 1992 304 78-82. 

Biosynthesis The endoperoxides PGG2 and PGH2 are formed in the so-called arachidonic acid cascade from eicosatetraenoic acid (arachidonic acid) liberated from membrane phospholipids by phospholipase A2 (EC 3.1.1.4) (see figure under thromboxanes) under the action of cyclooxygenase. All other PG are then formed by further enzymatic reactions. In contrast to other hormones, PG are not stored in the cell but are always newly synthesized when required. The close relatives of the PG, the thromboxanes, prostacyclins, leuko-trienes, and lipoxins are also generated from eicosa-polyenoic acids in the lipoxygenase pathway. For synthesis, see Ut.. ... 

This chapter is focused on the biosynthesis and actions of lipoxins, resolvins, protectins, and maresins. Each group of PUFA-derived lipid mediators has its own distinct biosynthetic pathways and features a specialized biological activity profile. 

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