Leukotrienes and lipoxins

This discovery led to coinage of the term leukotriene , based on the cellular source from which the material was obtained for that first successful molecular characterization, namely leukocytes, and the arrangement of three conjugated double bonds (triene) present in the molecule and causing specific absorption peaks in the ultraviolet (UV) spectrum. It was later discovered that a new UV 

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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 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. 

Brink C et al International Union of Pharmacology XXXVII. nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev 2003 55 195. [PMID 12615958]... 

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

Hormonal lipids. We have already considered a number of hormones that are not water-soluble but may have to be transported by carrier proteins to their sites of action. These include retinoic acid (Box 22-A), metabolites of vitamin D (Box 22-C), and the plateletactivating factor (Box 8-A). The last functions in the brain311 as well as in blood. Hormonal lipids also include the prostaglandins (Fig. 21-7), leukotrienes, and lipoxins (Fig. 21-8). These are products of the eicosenoid cascade or network, which is activated by receptors linked to phospholipase C (Fig. 11-9). Cera-mide formed by hydrolysis of sphingomyelin initiates... 

Norel X. and Brink C. (2004). The quest for new cysteinyl-leukotriene and lipoxin receptors recent clues. Pharmacol. Ther. 103 81-94. 

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. 

In this review, we first describe the paths and enzymes leading to prostaglandins, leukotrienes, and lipoxins. We then take each of our topics, separately dealing with leukotriene modulators followed by cyclooxygenase inhib-... 

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

Suh YJ, Yoon SH, Sampson AP, et al Specific immunoglobulin E for staphylococcal enterotoxins in nasal polyps from patients with aspirin-intolerant asthma. Clin Exp Allergy 2004 34 1270-1275. Perez-Novo CA, Watelet JB, Claeys C, van Cauwenberge P, Bachert C Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis. J Allergy Clin Immunol 2005 115 1189-1196. 

Fig. 35.10. Action of lipoxygenases in the formation of HPETEs and HETEs. Lipoxygenases add hydroperoxy groups at position 5, 12, or 15 with rearrangement of the double bond. HPETEs are unstable and are rapidly reduced to form HETEs or converted to leukotrienes and lipoxins (see Figs. 35.11 and 35.12).

Lindgren JA, Edenius C Transcellular biosynthesis of leukotrienes and lipoxins via leukotriene A4 transfer. Trends Pharmacol Sci 1993 14 351-354. 

Stenke L, Reizenstein P, Lindgren JA Leukotrienes and lipoxins - New potential performers in the regulation of human myelopoiesis. Leuk Res 1994 18 727-732. 

Claria J, Titos E, Jimenez W, Ros J, Gines P, Arroyo V, Rivera F, Rodes J Altered biosynthesis of leukotrienes and lipoxins and host defense disorders in patients with cirrhosis and ascites. Gastroenterology 1998 15 147—156. 

Brezinski DA, Nesto RW, Serhan CN Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy. Circulation 1992 86 56-63. 

Smith, W.L. and Garcia-Perez, A. (1980). A two-receptor model for the mechanism of action of prostaglandins in the renal collecting tubule. In Bailey, J.M. (ed.) Prostaglandins, Leukotrienes, and Lipoxins, pp. 35-45. (New York and London Plenum Press)... 

Prostaglandins are biosynthesized from the 20-carbon unsaturated fatty acid, arachidonic acid. Leukotrienes and lipoxins... 

Enzymatic oxidation of arachidonic acid also leads to two important classes of acyclic products, leukotrienes and lipoxins, that arise from oxidation at C-5 and/or C-15. 

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