Leukotrienes biological activities

Leukotriene. Biologically active compound functions as regulators of allergic and inflammatory reactions. They are identified by the letters A, B, C, D, and E, with subscripts indicating the number of double bonds in the molecule. 

The organization of Part Two is according to structural type. The first section, Chapter Seven, is concerned with the synthesis of macrocyclic compounds. Syntheses of a number of heterocyclic target structures appear in Chapter Eight. Sesquiterpenoids and polycyclic higher isoprenoids are dealt with in Chapters Nine and Ten, respectively. The remainder of Part Two describes syntheses of prostanoids (Chapter Eleven) and biologically active acyclic polyenes including leukotrienes and other eicosanoids (Chapter Twelve). 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Brain, S., Camp, K, Dowd, P., Kobza-Black, A. and Greaves, M. (1984). The release of leukotriene B4-like material in biologically active amounts from the lesional skin of patients with psoriasis. J. Invest. Dermatol. 83, 70-73. 

Fogh, K., Herlin, T. and Kr balle, K. (1989). Eicosanoids in acute and chronic psoriatic lesions leukotriene B4, but not 12-hydroxyeicosatetraenoic acid is present in biologically active amounts in acute lesions. J. Invest. Dermatol. 92, 837-841. 

K. R. and Roberts, L.J. (1990). Formation of unique biologically active prostaglandins in vivo by a non-cyclooxygenase free radical catalyzed mechanism. Adv. Prostagland. Thromboxanes Leukotriene Res. 21, 125-128. 

B. Samuelsson (1980). The leukotrienes a new group of biologically active compounds including slow reacting substance. Trends Pharmacol. Sci. 1 227-230. 

Prostaglandins (PG s) and leukotrienes (LT s) are biologically active derivatives of 20 carbon atom polyunsaturated essential fatty acids, which contains 3, 4 or 5 double bonds (e.g. 5,8,11,14-eicosatetraenoic acid i.e., arachidonic acid). 

This strategy to prepare rran.r,as-configurated functionalized dienes like 34 has elegantly been exploited for syntheses of HETEs (hydroxyeicosatetraenoic acids) and leukotrienes 27). These metabolites of arachidonic acid have received much attention due to thek biological activity. Syntheses of HETEs, for instance, follow the principle outlined in Eq. 12 with the acid catalysed ring opening of homofuran derivatives 36 to 37 as the stereoselective key step. 

The eicosanoids, a group of biologically active lipids that includes the prostaglandins and leukotrienes (Section 29.6) Vioxx, Bextra, and Celebrex—novel anti-inflammatory drugs (Section 29.6)... 

The leukotrienes are molecules that contribute to the asthmatic response. A typical example, leukotriene C4, is shown. Although its biological activity was first observed in the 1930s. the chemical structure of leukotriene C4 was not determined until 1979. Structure determination and chemical synthesis were difficult because leukotrienes are highly unstable and extremely potent, and are therefore present in tissues in exceedingly small amounts. 

The eicosanoids are a group of biologically active compounds containing 20 carbon atoms derived from arachidonic acid. The prostaglandins (Section 19.6) and the leukotrienes (Section 9.16) are two types of eicosanoids. Two others are the thromboxanes and prostacyclins. 

Dietary fat serves several important nutritional functions. It is the source of essential fatty acids. Members of the n-6 and n-3 (also known as the co-6 and co-3) families of fatty acids are important constituents of cell membranes and serve as precursors of eicosanoids (biologically active compounds such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes). Fat also serves as a carrier for the fat-soluble vitamins, and it is important source of energy. In addition, it has important culinary properties and contributes to the palatability of food. 

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