Lipoxins structure

Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN. Leuko-trienes and lipoxins structures, biosynthesis, and biological effects. Science 1987 237 1171-1176. 

A class of 5,6,15- and 5,14,15-trioxygenated metabolites of arachidonate has been described by Samuelsson et al. Two of these compounds, termed lipoxins A and B, have recently been assigned the structures shown below. 1 Outlined below is a synthesis of a putative biosynthetic precursor of these compounds. Syntheses of the structures assigned to lipoxins A and B have also been accomplished.3.4... 

Rats fed a purified nonlipid diet containing vitamins A and D exhibit a reduced growth rate and reproductive deficiency which may be cured by the addition of linoleic, a-linolenic, and arachidonic acids to the diet. These fatty acids are found in high concentrations in vegetable oils (Table 14-2) and in small amounts in animal carcasses. These essential fatty acids are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation (see below), and they also have various other functions which are less well defined. Essential fatty acids are found in the stmctural lipids of the cell, often in the 2 position of phospholipids, and are concerned with the structural integrity of the mitochondrial membrane. 

Fig. 7.2 Chemical structures of lipoxins, resolvins and neuroprotectins. Lipoxin A4 (a), Lipoxin B4 (b) 16,17S-docosatriene (c) 10,17S-docosatriene (d) 7,16,17S-resolvin (e) and 4S5,17S-resolvin (f). These metabolites retard the actions of arachidonic acid and its metabolites...

Chiang N, Takano T, Arita M, Watanabe S, Serhan CN (2003) A novel rat lipoxin A4 receptor that is conserved in structure and function. Br J Pharmacol 139 89—98... 

Lee TH, Lympany P, Crea AE, Spur BW Inhibition of leukotriene B4-induced neutrophil migration by lipoxin A4 Structure-function relationships. Biochem Biophys Res Commun 1991 ... 

Fig. 3.7 Chemical structures of DHA-, EPA-, and ARA-derived lipid mediators. Neuroprotectm Di (a) resolvin Dj (b) lipoxin A4 (LXA4) (c) lipoxin (LXB4) (d) EPA-derived lipoxin A5 (LXA5) (e) and EPA-derived leukotrienes (f)...

LIpoxins (LX). Acyclic eicosanoids with conjugated tetraene or pentaene structures and three hydroxy groups. The first identified compounds were designated as L. A and L. B with the index 4 or 5 to indicate the number of their C=C-double bonds. Biosyn-thetically L. are formed from arachidonic acid under the action of various oxidizing enzymes, especially 5- and 15-lipoxygenases. (55,6/J,155)-Trihydroxy-... 

Many other eicosanoids, such as thromboxanes, lipoxins, 0x0 eicosanoids, hydroperoxy eicosanoids, hydroxyeicosatetraenoic acids, epoxyeicosatetraenoic acids, and isoprostanes, are also biologically active molecules. ESI has emerged as an efficient ionization method for these classes of eicosanoids. An abundant carboxylate anion is produced in the negative-ion ESI mode [59]. Low-energy CID of the ESI-produced [M — H] ions of these molecular species produces structurally distinct ions for these disparate molecular species. 

The primary LOX metabolites, the hydroperoxy fatty acids, are further metabolized to an array of secondary products that may be classified into several groups according to their chemical structures (i) leukotrienes containing three conjugated double bonds, (ii) mono- and double-oxygenated polyenoic fatty acids that are not formed via a leukotriene intermediate and (iii) lipoxins and hepoxilins. 

Lipoxins constitute an additional family of bioactive LOX products which are characterized by a conjugated tetraene structure and three asymmetric carbons to which hydroxy groups are attached [25]. Lipoxins are abbreviated to LX followed by a capital letter (A or B) that indicates the position of the OH-groups, and by a subscript which gives the number of the double bonds. The biosynthesis of lipoxins [26,27] involves a concerted action of 5- and 15-LOXs or of 5- and 12-LOXs as well as an enzymic hydrolysis of an epoxide intermediate (Scheme 6). However, in vitro experiments with purified rabbit 15-LOX suggested that lipoxin B4 can be formed... 

Figure 1. Pathways and chemical structures for leukotriene and lipoxin biosynthesis. Enzymes responsible for known catalytic steps are noted in italics. AA, arachidonicacid.5-, 15-LOX, 5-, 15-lipoxygenase. 5-, 15-HETE, 5(5 )-, 15(5)-hydroxyeicosatetraenoicacid.5-, 15-HPETE, 5(5 )-, 15(5 )-hydroperoxyeicosatetraenoic acid. 5(6)-Epoxytetraene, 15(5)-hydroxy-5(6)-epoxy-7,9,13- ra. -ll-c/5-eicosatetraenoic acid. LTA, leukotriene A 5(6)-epoxy-7,9- rafZ5-ll,14-cw-eicosatetraenoic acid. LTB, leukotriene 5(5 ),12(/ )-dihydroxy-6,14-cw-8,10- rfl .y-eicosatetraenoic acid. LTC, peptido-leukotriene C 5(5)-hydroxy-6(/ )-5 -glutathione-7,9-fra 5-ll,14-cw-eicosatetraenoic acid. LTD, peptido-leukotriene D 5(5)-hydroxy-6(/ )-( S-cysteinylglycinyl)-7,9-rra 5-11,14-cA-eicosatetraenoic acid. LTE, peptido-leukotriene E 5(5)-hydroxy-6(/ )-( S-cysteinyl)-7,9-rra 5-ll,14-cw-eicosatetraenoic acid. LXA, lipoxin A 5(5 ),6(/ ), 15(5)-trihydroxy-7,9, 3-trans-11 -cA-eicosatetraenoic acid.

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