Arachidonic acid metabolism 35

Needleman, P, et al., 1986. Arachidonic acid metabolism. Annual Review of Biochemistry 55 69-102. 

Contrary to other elicitors of non-immune anaphylactic reactions (radiocontrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs (NSAIDs)) where there are at least hypothetical concepts regarding the pathomecha-nism of these reactions via increased mediator release (e.g. histamine release, shift in arachidonic acid metabolism from prostaglandins towards leukotrienes, etc.) [26], there is almost no literature regarding the pathomechanism of these reactions after LA application. 

By interfering with any one of the many phases associated with these second messenger pathways, toxins may alter channel gating. For example, the blue green algal toxins, aplysiatoxin, and lyngbyatoxin bind to and activate protein kinase C in a manner similar to phorbol esters (73). They also stimulate arachidonic acid metabolism (74). The coral toxin, palytoxin, also stimulates arachidonic acid breakdown albeit by an unknown mechanism (74) and affects other biochemical activities of the cell (see chapters by Fujiki et al., Wattenberg et al., and Levine et al., this volume). 

Table I. Cells in Which Arachidonic Acid Metabolism Is Stimulated by Palytoxin to Produce Cyclooxygenase Products ...

Palytoxin s properties of stimulating arachidonic acid metabolism were decreased > 90% after exposure to 0.1 N HCl for 60 min at 37 C and decreased about 75% after exposure to 0.01 N HCl for 60 min at 50 C, but these biologic properties were stable to boiling in H2O for 60 min. Palytoxin s serologic activities were stable to these treatments. 

Furthermore, we found that the two types of tumor promoters induced common biological effects, such as irritation of mouse ear, and stimulation of prostaglandin E2 production and of arachidonic acid metabolism in rat macrophages. These common effects seem to be the most essential biological activities in tumor promotion (6). 

Adler, K.B., Akiey, N.J. and Holdenstaufier, W.J. (1989). Exposure of airway epithelium to extracellular oxidants in vitro stimulates arachidonic acid metabolism and mucin secretion. Am. Rev. Resp. Dis. 139, A403. 

The source of free radicals is multiplied under these circumstances, arachidonic acid metabolism, activation of xanthine oxidase, perturbation of electron flow within the respiratory chain, and NOS activation. Structurally, excitotoxicity is generally described as a necrotic process involving initial swelling of the cell and of the endoplasmic reticulum, clumping of chromatin, followed by swelling of the... 

The title compound 160, a biologically potent metabolite of arachidonic acid metabolism, produced in the 5-lipoxygenase pathway in some mammalian cells127 128, has been synthesized129-131 by the reaction of leukotriene E4, 161, with [l-nC[acetyl chloride in 1.3% yield based on [l-nC] acetyl chloride129 (equation 55). 

Mitochondria, nitric oxide synthase and arachidonic acid metabolism are sources of reactive oxygen species during ischemia—reperfusion injury 568... 

Mitochondria, nitric oxide synthase and arachidonic acid metabolism are sources of reactive oxygen species during ischemia-reperfusion injury. ROS generation during ischemia-reperfusion may come from several sources, including NOS activity, mitochondrial electron transport, multiple steps in the metabolism of arachidonic... 

Kolko, M., DeCoster, M. A., Rodriguez de Turco, E. B. and Bazan, N. G. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures./. Biol. Chem. 271 32722-32728,1996. 

The 5-lipoxygenase pathway of arachidonic acid metabolism is responsible for production of cysteinyl leukotrienes. Leukotrienes C4, D4, and E4 are released during inflammatory processes in the lung and produce broncho-spasm, mucus secretion, microvascular permeability, and airway edema. 

Lawrence, B.P. and Kerkvliet, N.I., Role of altered arachidonic acid metabolism in 2,3,7,8-lelrachlorodibenzo-p-dioxin-induced immune suppression in C57B1/6 mice, Toxicol. Sci., 42, 13, 1998. 

Bornfeldt, K. E., Axelsson, K. L., Studies on the effect of different inhibitors of arachidonic acid metabolism on glyceryl trinitrite-induced relaxation and cGMP elevation in bovine vascular tissue. Pharmacol. Toxicol. 60 (1987),... 

Steinbeck, M. J., Webb, D. S. A., Roth, J. A. (1989). Role for arachidonic acid metabolism and protein synthesis in recombinant bovine interferon- /induced activation of bovine neutrophils. J. Leuk. Biol. 46, 450-60. 

M. Moghaddam, K. Motoba, B. Borhan, F. Pinot, B. D. Hammock, Novel Metabolic Pathways for Linoleic and Arachidonic Acid Metabolism , Biochim. Biophys. Acta 1996, 1290, 327 - 339. 

Srivastava KC. (1984). Aqueous extracts of onion, garlic and ginger inhibit platelet aggregation and alter arachidonic acid metabolism. Biomed Biochim Acta. 43(8-9) S335-46. 

Capasso F. (1986). The effect of an aqueous extract of Tanacetum parthenium L. on arachidonic acid metabolism by rat peritoneal leucocytes. J Pharm Pharmacol. 38(1) 71-72. 

F i g u re 18.1 One pathway of arachidonic acid metabolism. The branches of this pathway lead to the prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TxBs). The key reaction is the formation of PGH2, creating five chiral centers from an achiral molecule. (Modified from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. Reprinted with permission John Wiley and Sons Inc.)... 

D. Washo-Stultz, C. L. Crowley-Weber, K. Dvorakova, C. Bernstein, H. Bernstein, K. Kunke, C. N. Waltmire, H. Garewal and C. M. Payne, Role of mitochondrial complexes I and II, reactive oxygen species and arachidonic acid metabolism in deoxycholate-induced apoptosis. Cancer Lett., 2002, 177(2), 129. 

Leukotrienes are products of arachidonic acid metabolism and are released from mast cells and eosinophils. Leukotrienes and leukotriene receptor occupation have been correlated with airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. 

Another important aspect of the inflammatory cascade is arachidonic acid metabolism, leading to the synthesis of the proinflammatory prostaglandins and leukotrienes. Through the formation of Upocortin, an inhibitor of phospholipase A2, glucocorticoids depress the release of arachidonic acid from phospholipids and hence the production of arachidonic acid metabolites. 

HV051 Sekiya, K., T. Fushimi, T. Kanamori, et al. Regulation of arachidonic acid metabolism in platelets by vegetables. 

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