Leucotrienes

Lipoxygenase AVNTR polymorphism in 100 bp upstream from the ATG start codon is associated with transcription efficiency. Differences in response to 5-lipoxygenase inhibitors and leucotriene receptor antagonists. 

Halliwell, B. and Gutteridge, J.M.C. (1989). Eicosanoids prostaglandins and leucotrienes. In Free Radicals in Biology and Medicine pp. 401-403. Clarendon Press, Oxford. 

A summary of the processes for producing the eicosanoids from the polyunsaturated fatty acid, arachidonic acid, is presented in Figure 11.27. The two enzymes separate for synthesising the prostanoids or the leucotrienes are cyclooxygenase and lipoxygenase, respectively. Whether prostanoids or leucotrienes are produced in any given tissue will depend on the relative activities of these two enzymes in that tissue. 

The leucotrienes, lipoxins and hydroperoxy fatty acids are also synthesised from arachidoific acid. The initial enzyme... 

The two essential fatty acids of most biochemical and clinical interest are arachidonic acid, which gives rise to prostanoids of series 2 and leucotrienes of series 4, and eicosapentaenoic acid, which gives rise to prostanoids of... 

Figure 11.32 Formation of prostaglandins of the 2 and 3 series and leucotrienes of the 4 and 5 series from arachidonic acid and eicosapentaenoic acid.

Histamine Prostagiandins Leucotrienes Cationic proteins Proteoiytic enzymes Serotonin... 

Trans fatty acids are produced during the commercial hydrogenation of plant oils (Chapter 11). Some margarines contain these fatty acids, as do some commercially prepared snack foods (e.g. biscnits, cookies, cakes, crisps, chips). In addition, bacteria in the rnmen of rnminants prodnce trans fatty acids, which are therefore present in dairy prodnce and meat. Trans fatty acids can be incorporated into the phospholipids of the plasma membrane of endothelial and other cells, resulting in damage to the membranes. Furthermore, these abnormal fatty acids can interfere in the production of thromboxanes, prostacyclins or leucotrienes and hence interfere in control of blood clotting, immune cell activity and inflammation (Chapter 11). 

Table 4. Measured and calculated log P values (Clog P) of leucotriene antagonists [42]... 

MK-0571, 344, potent antagonist of LTD4306, has been synthesized307 to evaluate the role of leucotriene D4 in human disease states. 344 has been obtained by exchange between diacid 345 and 3-[35S]mercaptopropanoic acid in trifluoroacetic acid (equation 179). 346 has been generated from 348 prepared as shown in equations 180 and 181. 

The anti-inflammatory activity of curcumin and its derivatives is associated with the hydroxyl and phenol groups in the molecule, which are also essential for the inhibition of prostaglandins, PG synthetase and leucotriene synthesis (LT) (Kiuchi et al., 1982, 1992 Iwakami, et al, 1986). Claeson et al. (1993, 1996) suggested that the antiinflammatory action and the antiparasitic activity were associated with the (3-dicarbo-nylic system with conjugated double bonds (dienes) (Araujo et al., 1998, 1999). The better skin penetration and lipophylicity is attributed to the presence of a diene ketone system. Calebin-A, a novel curcuminoid isolated from turmeric, protects neuronal cells from (3-amyloid insult. The hydroxy group at para-position of this compound is most critical for the expression of biological activity (Kim et al., 2001). 

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