Oxygen arachidonic acid cascade

Sulfasalazine. Salicylazosulfapyridine or Azulfadine [599-79-1] (2-hydroxy-5-[[4[(2-pyridylamino)sulfonyl]-phenyl]azo] benzoic acid) (15) is a light brownish yellow-to-bright yellow fine powder that is practically tasteless and odorless. It melts at ca 255°C with decomposition, is very slightly soluble in ethanol, is practically insoluble in water, diethyl ether, chloroform, and benzene, and is soluble in aqueous solutions of alkali hydroxides. Sulfasalazine may be made by the synthesis described in Reference 13. It is not used as an antidiarrheal as such, but is indicated for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn s disease. Its action is purported to result from the breakdown in the colon to 5-aminosalicylic acid [89-57-6] (5-AS A) and sulfapyridine [144-83-2]. It may cause infertility in males, as well as producing idiosyncratic reactions in some patients these reactions have been attributed to the sulfa component of the compound. The mechanism of 5-ASA is attributed to inhibition of the arachidonic acid cascade preventing leukotriene B4 production and the ability to scavenge oxygen free radicals. The active component appears to be 5-aminosalicylic acid. 

Prostaglandin H synthase is the first enzyme involved in the arachidonic acid cascade . The prostaglandins can cause both relaxation and tension in smooth muscle and so have vital physiological roles. Prostaglandin H synthase acts as both a peroxidase and an oxygenase its so-called cyclooxygenase activity involves addition of two equivalents of oxygen to a free radical derived from arachidonic acid to form an endoperoxide... 

In many of the pathological conditions of the brain in which eicosanoid production is increased, it has been found or speculated that there is production of oxygen-free radicals, and that lipid peroxidation occurs. The chemistry of these species is considered briefly, since their effects on brain structure and function may be additive to those of eicosanoids. Moreover both interact with the arachidonic acid cascade and can modify eicosanoid production. 

The arachidonate cascade includes the COX pathway to form prostanoids and the lipoxygenase (LOX) pathway to generate several oxygenated fatty acids, collectively called eicosanoids. While the exact mechanism remains unknown, it has been shown that eicosanoids play a dual role in regulating both cell survival and apoptosis in various types of cells [81]. One recent study, for example, demonstrated that arachidonic acid metabolites are involved in the regulation of apoptosis in human polymorphonuclear neutrophil granulocytes [82],... 

C20H32O2, Mr 304.47, mp. -49.5 °C, bp. 163°C (133 Pa). A biochemically important essential fatty acid, precursor of various eicosanoids. In animals, A. is formed in several steps from linoleic acid by introduction of 2 double bonds and chain extension by 2 carbon atoms linoleic acid - y- linolenic acid - di-homo-y-linolenic acid arachidonic acid. In nature A. occurs in animal lipids, especially in phospholipids of cell membranes, from which phospholipase A2 releases A. on stimulation by hormones or mediators. A. serves as starting material for the biosynthesis of numerous physiologically active oxygen derivatives (especially hydroxy-, hydroperoxy-, and epoxy compounds) known as the eicosanoids. Their separation into different groups in the so-called A. cascade is shown in the figure... 

Figure 11.17. Examples of unsaturated fatty acids. Large numbers of such alkenes both as ( )- and (Z)-isomers exist. The intermediate in the oxidation of arachidonic acid to (only one shown member of the) prostaglandins is part of a cascade of reactions to an entire family of compounds that vary in oxidation state. Leukotrienes (three conjugated double bonds and no five-membered ring) and thromboxanes with six-membered oxygen-containing rings (oxa-cyclohexane, pyran, oxane) are also derived from C20 polyalkenes.

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