Platelet activating factor phospholipases

Sawai, H., Domae, N., Nagan, N., and Hannun, Y. A. Function of the Cloned Putative Neutral Sphingomyehnase as Lyso-platelet Activating Factor-Phospholipase C. J Biol Chem 274 (1999) 38131-38139. 

Hendrickson, H. S., Hendrickson, E. K., Johnson, I. D. and Farber, S. A. (1999). Intramolecularly quenched BODIPY-labeled phospholipid analogs in phospholipase A(2) and platelet-activating factor acetylhydrolase assays and in vivo fluorescence imaging. Anal. Biochem. 276, 27-35. 

Esterases play a role in regulating the platelet-activating factor (PAF), a lipid with hypotensive properties [96], Phospholipase A2 (EC 3.1.1.4) is involved in this pathway by hydrolyzing a precursor to lyso-PAF and a free fatty acid. The activity of PAF, formed by acetylation of lyso-PAF, is controlled by an esterase hydrolyzing the acetate moiety [100]. 

L. W. Tjoelker, C. Eberhardt, J. Unger, H. Letrong, G. A. Zimmerman, T. M. McIntyre, D. M. Stafforini, S. M. Prescott, P. W. Gray, Plasma Platelet-Activating Factor Acetyl-hydrolase Is a Secreted Phospholipase A2 with a Catalytic Triad ,./. Biol. Chem. 1995, 270, 25481-25487. 

Since predators of snakes (and humans) have to deal with snake venoms as defenses, they are included here, even though they serve in predation. Snake venoms are primarily enzymes (proteins), especially of the phospholipase A2 type, which breaks down cell membrane phospholipids hydrolytically. Other snake venoms such as cobrotoxin contain peptides with 60-70 amino acid residues. Pharmacologically, they have neurotoxic, cytotoxic, anticoagulant, and other effects. The neurotoxins, in turn, can have pre- or postsynaptic effects. Snake venoms with both neurotoxic and hemolytic effects on the heart are known as cardiotoxins. Cytotoxins attach to the cells of blood vessels and cause hemorrhage. Snake venom factors may stimulate or inhibit blood clotting. Finally, platelet-active factors can contribute to hemorrhage. 

In addition to their effects on leukocyte function, glucocorticoids influence the inflammatory response by reducing the prostaglandin, leukotriene, and platelet-activating factor synthesis that results from activation of phospholipase - Finally, glucocorticoids reduce expression... 

FI Naraba, Y Imai, I Kudo, Y Nakagawa, S Oh-ishi. Activation of phospholipase A2 and acylation of lysophospholipids the major regulators for platelet activating factor production in rat neutrophils. J Biochem (Tokyo) 118 442-447, 1995. 

Hakkinen, T, Luoma, JS, Hiltunen, MO, Macphee, CH, Milliner, KJ, Patel, L, Rice, SQ, Tew, DG, Karkola, K, and Yla-Herttuala, 1999, Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions, Arterioscler. Thromb. Vase. Biol. 19 2909-2917. 

Dhar A, Shukla SD. Electrotranqection of pp60v-src monoclonal antibcxly inhibits activation of phospholipase C in platelets. A new mechanism for platelet-activating factor responses. J Biol Chem 1994 269 9123-9127... 

Kramer RM, Jakubowski JA, and Deykin D. (1988). Hydrolysis of l-aikyl-2-aradtidonoyl-sn-glycero -3-pbosphocholine, a common precursor of platelet-activating factor and eicosanoids, by human platelet phospholipase A2. Biodiim. Biophys. Acta 959,269-279. 

Concerning mediators of immediate hypersensitivity, the most important include histamine, leukotriene e.g., SRS-A (slow-reacting substance of anaphylaxis, ECF-A (eosinophil chemotactic factor of anaphylaxis), PAF (platelet-activating factor), and serotonin. There are also three classes of lipid mediators that are synthesized by activated mast cells through reactions initiated by the actions of phospholipase A2. These are prostaglandins, leukotrienes, and platelet-activating factors (PAF). 

Phospholipase AjS (PLAjs) hydrolyze the sn-1 fatty acid residue from phospholipids and produce mostly saturated or mono-unsaturated fatty acids and 2-acyl-lyso-phosphohpids. PLAjS have not attracted as much attention as mammalian acylhy-drolases, PLA2S, which are involved in the production of bio-active hpids such as prostanoids and platelet-activating factor (PAP) [1, 2]. 

Tjoelker LW. Eberhardt C, Unger J, et al. (1995) Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad. J Biol Chem 270 25481-25487... 

Fig. 13. Catabolism of platelet-activating factor (PAF) and its metabolites by (I) PAF-AH, (II) lysophospholipase D, (III) phosphohydrolase, (IV) phospholipase C, (V) Cok-independent or CoA-dependenI transacylase, and/or (VI) alkylacetylglycerol acetylhydrolase. The O-alkyl linkage in products that contain free hydroxyl groups can be cleaved by (VII) the O-alkyl Pte H4-dependent monooxygenase.

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