Prostaglandins and leukotriene biosynthesis

Kiuchi F, Iwakami S, Shibuya M, Hanaoka F, Sankawa U. (1992). Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharm Bull (Tol o). 40(2) 387-91. Kobayashi M, Shqji N, Ohizumi Y. (1987). Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum. Biochim Biophys Acta. 903(1) 96-102. 

Hanaoka, and U. Sankawa. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diaryl-heptanoids. Chem Pharm Bull 1992 40(2) 387-391. 

Kozubik, A., J. Hofmanova, J. Hola, and J. Netikova. 1993. The effect of nordihydroguaiaretic acid, an inhibitor of prostaglandin and leukotriene biosynthesis, on hematopoiesis of gamma-irradiated mice. Exp. Hematol. 21(1) 138-142. 

Peptideglycan biosynthesis Metabolism of Complex Lipids Glycerolipid metabolism Inositol phosphate metabolism Sphingophospholipid biosynthesis Phospholipid degradation Sphingoglycolipid metabolism Prostaglandin and leukotriene metabolism... 

Figure 8.9 Prostaglandins and leukotrienes are potent eicosanoid lipid mediators, derived from phospholipase-released arachidonic acids, that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and pharmacological actions are inhibited by clinically relevant nonsteroidal anti-inflammatory drugs.

Evidence indicates that steroids affect other cells and substances that modulate inflammation. Exposure of human basophils to steroid in culture inhibits histamine release induced by an IgE-dependent stimulus. Steroids inhibit phospholipase A2, which prevents biosynthesis of arachidonic acid and subsequent formation of prostacyclin, thromboxane A, prostaglandins, and leukotrienes. Steroids also decrease capillary permeability and fibroblast proliferation and the quantity of collagen deposition, thereby influencing tissue regeneration and repair. 

Inhibition of prostaglandin, thromboxane and leukotriene biosynthesis. 15. Ill Integrated control of trematode diseases. 12. 53 Interethnic factors affecting drug response. 25. 1 Interferon and interferon inducers. 10, 101... 

In addition to the conversion of unactivated alkanes to alcohols, cytochrome P450 hemes transform alkenes to epoxides, arenes to phenols, and sulfides to sulfoxides to sulfones. Furthermore, they are involved in the biosynthesis and biodegradation of endogenous compounds such as steroids, fatty acids, prostaglandins and leukotrienes. Under anaerobic conditions, P450 will reductively dehalogenate haloalkanes to the corresponding alkanes. 

AP (apuiinic) site a site, lacking a purine base in DNA, that IS targeted by repair enzymes (10.5) arachidonic acid a fatty acid that contains 20 carbon atoms and 4 double bonds the precursor of prostaglandins and leukotrienes (8.8) aspartate transcarbamo)lase (ATCase) a classic example of an allosteric enzyme that catalyzes an early reaction in pyrimidine biosynthesis (6.5)... 

Alternatively, an e ifo-peroxide may be formed, whose reduction leads to a diol (Eq. 2-8). The latter reaction resembles the cycloadditon of singlet-oxygen onto an unsaturated system and occurs in the biosynthesis of prostaglandins and leukotrienes. Both intermediate hydro- or e peroxide species are highly reactive and may be subject to further transformations such as (enzymatic or non-enzymatic) reduction or rearrangement. 

Figure 1.9. Overview of the biosynthesis of ecosanoids. The 20 carbon fatty acid arachidonic acid is released from cell membrane phospholipids by the actions of phospholipase A2. Free arachidonic acid forms the precursor of prostaglandins and thromboxanes via the multi-enz5une cyclooxygenase pathway, while leukotrienes are formed via the lipoxygenase pathway...

Figure 3 Simple schema of the biosynthesis of prostaglandins (PG), thromboxanes (TX), and leukotrienes from arachidonic acid consequent to cell injury (modified after Bonica, 1990).

Figure 2. Biosynthesis of prostaglandins, thromboxanes, prostacyclins, and leukotrienes.

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