Phospholipase platelet metabolism

The enzymes responsible for the platelet metabolism are distributed in different platelet structures, For example, the plasma membrane contains adenylate cyclase in contrast, phospholipase (PL) A2, diglycerol lipase, cyclooxygenase... 

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. 

Stimulated platelets release arachidonic acid rapidly from their phospholipids, apparently as a result of activation of phospholipase A2. The released arachidonate can in turn be metabolized to endoperoxides and thromboxane A2 (Chapter 21). These compounds are also potent activators of platelets and cause a self-activating or autocrine effect.1) While PAF has a beneficial function, it can under some conditions contribute in a dangerous way to inflammation and to allergic responses including anaphylaxis,) asthmag and cold-induced urticaria.1 Although the effect of PAF is separate from those of histamine and of leukotrienes, these agents may act cooperatively to induce inflammation.1... 

Metabolism of membrane phospholipids may be also a target for the action of cGMP. Indeed, the inhibition of both phospholipase C and A has been implicated in the mechanism of this action on platelets (Nakashima et al, 1986 Sane et al, 1989). 

Recently Liu and Weller [84] have reviewed the arachidonic acid metabolism in filarial parasites and other helminths. Arachidonic acid (AA) is a 20 carbon polyunsaturated fatty acid derived from dietary fatty acids. In human tissues, AA is usually present in the esterified form such as glycerolipids, phospholipids and neutral lipids. The free AA, released by phospholipases, undergoes various enzymatic oxygenations to form local mediators such as prostaglandins and leukotrienes, which are collectively known as eicosanoids (Chart 9). These eicosanoids are associated with platelet aggregation, vasodilation, leukocyte inflammatory and immune functions and cellular adhesion [85]. 

Sato, T.. Aoki, J Nagai, Y Dohmae, N Takio, K Doi, T.. Arai, H., and Inoue, K. (1997), Serine phospholipid-specific phospholipase A that is secreted from activated platelets, A new member of the lipase family. J. Biol Chem. 211, 2192-2198. Seifert, J., and Pewnim, T. (1992), Alteration of mice L-tryptophan metabolism by the organophosphorous acid iriester diatrinon. Biochem. Pharmacol. 44, 2243-2250. 

The mechanism of an increased phosphatidylinositol metabolism has been studied in platelets stimulated with thrombin in some detail. Thrombin stimulation leads to formation of the 1,2-diacylglyceride and inositol phosphate through hydrolysis by phospholipase C (Fig. 4). According to Majerus and coworkers, the diacylglyceride is then hydrolysed by a diglyceride lipase with liberation of arachidonic acid [35,40]. In contrast, Lapetina and his colleagues [41,42] propose that the diacylglyceride is phosphorylated to phosphatidic acid, a likely calcium ionophore [43], which in turn... 

PDGF is synthesized and released not only by activated platelets but also by monocytes, endothelial cells, or (embryonal) smooth muscle cells, and it binds to specific receptors of target cells such as monocytes, polymorphonuclear leukocytes (PMN), smooth muscle cells, and fibroblasts. It is important to consider that PDGF is able both to provoke full expression of the entire PMN activation response and to promote the full sequence of monocyte activation [120]. Elevated levels of plasma lipoproteins, especially low- and very low density fractions, may be iqjurious to the endothelium [S4], may permit monocyte adhesion, induce growth factor formation [74], and seem to be linked to arachidonic acid metabolism [46]. Furthermore, it has been demonstrated in cell culture systems that PDGF leads to subsequent activation of the phospholipase C/diglyceride... 

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