Lipoxins Lipoxygenase

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 ...

Eicosanoid synthesis. Arachidonic acid is converted by cyclooxygenases into prostaglandins, and thromboxanes. Lipoxygenases convert arachidonic acid into HPETEs, which are then converted to lipoxins, leukotrienes, and 12-HETE (hydroxyeicosatetraenoic acid). Epoxygenases convert arachidonic acid into epoxides. 

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

Another group of 5-lipoxygenase products are the lipoxins LXA and LXB. Their biologic roles are still to be defined. 

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... 

Lipoxygenases (LOs) are nonheme, mononuclear iron enzymes that catalyze the regio- and stereoselective conversion of polyunsaturated fatty acids with a di.di-1,4-diene functionality into products having a l-hydroperoxy-tra 5, cM-2,4-diene functionality. The mammalian LOs typically act on arachidonic acid and produce alkyl hydroperoxides that are converted into leukotrienes and lipoxins, which are involved as messengers in the inflammatory response. Plant enzymes act on linoleic acid, but the role of the product alkyl hydroperoxide is less well understood. 

Lipoxins are lipoxygenase-derived eicosanoids that probably dovm-regulate inflammation in the... 

W.J. Griffiths, Y.Yang, J. Sjovall, J.A. Lindgren, ESI-CID of mono-, di- and trihydroxylated lipoxygenase products, including LTB and lipoxins. Rapid Commun. Mass Spectrom., 10 (1996) 183. 

Serhan CN, Sheppard K-A. 1990. Lipoxin formation during human neutrophil-platelet interactions evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro. J. Clin. Invest. 85 772-80... 

Bafica A, Scanga CA, Serhan C, Machado E, White S, Sher A, Aliberti J (2005) Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J Clin Invest 115 1601-1606... 

Bannenberg GL, Aliberti J, Hong S, Sher A, Serhan C (2004) Exogenous pathogen and plant 15-lipoxygenase initiate endogenous lipoxin A4 biosynthesis. J Exp Med 199 515—523... 

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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