Arachidonic acid, conversion

NSAIDs usually do not inhibit lipoxygenase activity at concentrations that inhibit COX activity. In fact, by preventing arachidonic acid conversion via the COX pathway, NSAIDs may cause more substrate to be metabolized through the lipoxygenase pathways, leading to an increased formation of the inflammatory leukotrienes. Even among the COX-dependent pathways, inhibiting the... 

Other investigators have shown that oily garlic extracts, which contain ajoene, are able to inhibit enzymes necessary for arachidonic acid conversion to thromboxane (Srivastava anad Tyagi, 1993). Makheja et al. (1979) demonstrated the effect of garlic oil on platelet thromboxane synthesis. Human and rabbit platelets were incubated with garlic oil, resulting in almost complete... 

TXA2 is produced by activated platelets via the sequential conversion of arachidonic acid by phospholipase A2, cyclooxygenase-1 (COX-1), and thromboxane synthase. Similar to ADP, TXA2 acts as a... 

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

FIGURE 4.22 Prostaglandin H synthase-mediated conversion of arachidonic acid to PGH2. 

LO catalyses the stereospecific conversion of arachidonic acid (1) to a 5-hydroperoxyeicosatetraenoic acid (5-HPETE) (2). The enzyme contains... 

The acid-soluble SH-groups in platelets are mainly those of glutathione (GSH). GSH is a cofactor for enzymes such as peroxidase. If feverfew is able to interfere with this cofactor, enzyme function may be impaired. One pathway that may be affected in this way is the metabolism of arachidonic acid (Figure 6.1). In the presence of feverfew extract an increase was found in lipoxygenase product formation and impaired conversion of HPETE to HETE, for which GSH is a cofactor [52]. Inhibition of the liberation of [ " C]arachidonic acid from phospholipids was also found [53], which implies impairment of phospholipase A2 activity and for which SH-groups are thought to be important. 

Cyclooxygenase converts arachidonic acid first to prostaglandin G (PGG) and then to PGH prior to formation of prostaglandins, thromboxanes and prostacyclins. The structures of the intermediates and some of the end-products of these conversions are provided in Figure 11.28. 

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