Lipoxins

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

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... 

Brink C, Dahlen S, Drazen J et al (2003) Internation Union of Pharmacology XXXVILNomenclature for Leukotriene and Lipoxin receptors. Pharmacol Review 55 195-227... 

Eicosanoids These compounds, derived from eicosa- (20-carbon) polyenoic fatty acids, comprise the prostanoids, leukotrienes (LTs), and lipoxins (LXs). Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs). 

Eicosanoids are formed from 20-carbon polyunsaturated fatty acids and make up an important group of physiologically and pharmacologically active compounds known as prostaglandins, thromboxanes, leukotrienes, and lipoxins. 

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. 

Leukotrienes Lipoxins LXA4 LXB4 LXC4 LXD4 LXE4... 

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 ...

Leukotrlenes LIpoxIns Are Potent Regulators of Many Disease Processes... 

Serhan CN Lipoxin biosynthesis and its impact in inflammatory and vascular events. Biochim Biophys Acta 1994 1212 1. 

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

Schreiber s model has also proved to be a general approach to a series of oxygenated metabolites of arachidonic acid, such as lipoxin A and lipoxin B.50 The family of linear oxygenated metabolites of arachidonic acid has been implicated in immediate hypersensitivity reactions, inflammation, and a number of other health problems. Among these metabolites, several compounds, such as lipoxin A, lipoxin B, 5,6-diHETE, and 14,15-diHETE possess 1-substituted (/ )-1 -alken-3.4-diol 84 as a common substructural moiety. Therefore, the car-binol 83 is an ideal substrate for generating compound 84 by applying Sharpless epoxidation reaction.50... 

---