Phospholipase 13 pathways

It is fitting to introduce the phospholipase pathways here because they are controlled by small G proteins. Phospholipases C and D (PLC, PLD) are controlled by Rho/Arf and Cdc42 and Src tyrosine kinases participate in the control of PLD. 36 Phospholipases form potent second messengers, such as inositol trisphosphate (IP3) and diacylglycerol (DAG). In Fig. 4.6a the reactions catalysed by phospholipases C and D and the connections between phospholipases C and D are summarized, and in Fig. 4.6b the regulatory pathways that activate phospholipase D synergistically are summarized.37... 

Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi R, Arai H (2002) Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem 277 48737 8744... 

The release of 32 nmol of arachidonic acid per 10 platelets obtained using 5U/ml thrombin represents the hydrolysis of approximately 25% of the total arachidonate present in platelet phospholipids (Table 1.1) and is approximately twice the mass of phosphatidylinositol. Thus, the total hydrolysis of phosphatidylinositol by either a phospholipase pathway acting on this phospholipid or a phospholipase C-diglyceride lipase pathway could at the... 

Pasteurella multocida toxin (PMT) is the major pathogenic factor responsible for atrophic rhinitis, a disease which is characterized by bone loss in the nose of pigs. PMT is a 145 kDa single-chain exotoxin, which activates Goq protein (but not Gan) and stimulates phospholipase C 3. In addition, G12/i3 proteins and subsequently Rho pathways are activated. 

There are three groups of eicosanoids that are synthesized from C20 eicosanoic acids derived from the essential fatty acids linoleate and a-linolenate, or directly from dietary arachidonate and eicosapentaenoate (Figure 23-5). Arachidonate, usually derived from the 2 position of phospholipids in the plasma membrane by the action of phospholipase Aj (Figure 24-6)—but also from the diet—is the substrate for the synthesis of the PG2, 1X2 series (prostanoids) by the cyclooxygenase pathway, or the LT4 and LX4 series by the lipoxygenase pathway, with the two pathways competing for the arachidonate substrate (Figure 23-5). 

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). 

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