Phospholipases turnover

Other enzymes present in myelin include those involved in phosphoinositide metabolism phosphatidylinositol kinase, diphosphoinositide kinase, the corresponding phosphatases and diglyceride kinases. These are of interest because of the high concentration of polyphosphoinositides of myelin and the rapid turnover of their phosphate groups. This area of research has expanded towards characterization of signal transduction system(s), with evidence of G proteins and phospholipases C and D in myelin. 

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

In contrast to their more highly expressed counterparts, the 3-phosphoinositides do not serve as substrates for phospholipase C (PLC), the enzyme known to be activated in stimulated phosphoinositide turnover. This observation indicates that the 3-phosphoinositides themselves, rather than their breakdown products, are likely to... 

Phospholipid turnover also takes place in an asymmetric manner. The enzymes responsible for phospholipid turnover in response to receptor-mediated phospholipase c activation are active from the cytoplasmic surface of the membrane. Likewise, diacylglycerol kinases converting the product of phospholipase c back into the key intermediate of phospholipid biosynthesis, phosphatidic acid, are also located on the cytoplasmic smface of the membrane (Sanjuan et al., 2001). 

DC 196 Kleinig, H., and C. Kopp. Lipids, lipid DC208 turnover, and phospholipase D in plant suspension culture cells (Daucus carota). Planta 1978 139(1) 61-65. 

Further support for the hypothesis that Ca2+ plays a central role in regulating phytoalexin accumulation is provided by experiments in which the turnover of phosphatidylinositol was measured in the plasma membrane of elicitor-treated carrot cells [17]. The carrot cells were first labelled with [3H]myo-inositol and, after the addition of elicitors, acid extracts of the cells were analyzed chromatographically for the production of inositol trisphosphate (IP3). In cells treated with elicitor, the release of radioactive IP3 increased with time and attained a maximum at 3 - 5 min after treatment. Phospholipase activity responsible for the degradation of phosphorylated phosphatidylinositol increased correspondingly. Several reports have shown that IP3 induces rapid release of Ca2+ from intracellular stores in animal cells [18, 19]. Studies on plant cells have also demonstrated that exogenous IP3 releases Ca2+ from microsomal preparations at micromolar concentrations, although only limited... 

Very recent efforts to further evaluate the functional implications of phosphoinositol signaling in vertebrate chemosensory transduction have led to the discovery that not only the phosphoinositol breakdown pathway catalyzed by phospholipase C, but also membrane phosphoinositols themselves involving phosphoinositide-3-kinase may play a functional role in the transduction process. It was found that 3-phosphoinositides signaling in concert with the canonical phosphoinositide turnover pathway modulate the cyclic nucleotide signaling cascade downstream of the receptor. The data suggest that 3-phosphoinositide, the primary product of PI3K activity, attenuates the cyclic nucleotide-dependent excitation of olfactory neurons (Spehr et al., 2002). 

Munnik, T., Van Himbergen, J.A.J., Ter Riet, B., Braun, F.-J., Irvine, F.F., Van den Ende, H. and Musgrave, A., 1998b, Detailed analysis of the turnover of polyphosphoinositides and phosphatidic acid upon activation of phospholipases C and D in Chlamydomonas cells treated with non-permeabilizing concentrations of mastoparan. Planta 207 133-145. 

Phospholipase C A family of intracellular enzymes central to many signal transduction pathways via effects on Ca + and protein kinase C. Phospholipase C catalyzes the hydrolysis of phosphoinositol 4,5-bisphosphate to yield 1,4,5-inositol triphosphate and diacylglycerol. See Irvine, R.F., The enzymology of stimulated inositol lipid turnover. Cell Calcium 3, 295-309,1982 Farese, R.V., Phospholipids as intermediates in hormone action. Mol. Cell Endocrinol. 35,1-14,1984 Majerus, P.W., The production... 

The rate-limiting step in the biosynthesis of eicosanoids is the availabiUty of free precursor, unesterified AA (20 4, o)-6), for both cyclooxygenase (COX) and lipoxygenase en2ymes (13). The initial mobilization cellular AA (20 4, (0-6) is an essential step in the synthesis of eicosanoids (14, 15). Cellular AA is known to be exclusively associated with membrane phospholipids (16-18). It is also tigfrtly regulated through enzymes of the Lands cycle. The enzymes such as phospholipase Aj, arachidonoyl-CoA synthetase and lysophosphatidyl acyltransferases appear to be simultaneously active in order to maintain a steady turnover of AA (20 4, -6) (19). Platelets contain arachidonoyl CoA synthetase (20). 

Chock, S. P., Rhee,S. G.,Tang, L. C., andSchmauder-Chock, A. (1991). Linking phospholipase A2 to phospholipid turnover and prostaglandin synthesis in mast cell granules. Eur.J. Biochem. 195, 707-713. 

It has now been established by studies of numerous tissues that the interaction of all members of the Nk receptor family with appropriate ligands results in G protein-linked activation of phospholipase C and phos-phoinositol turnover with increased synthesis of inositol triphosphate (IPs) and consequent increases in levels of intracellular calcium (Nakanishi et al., 1993). This activation occurs via a pertussis toxin-insensitive pathway and probably involves the Gq/11 subfamily of Ga proteins (Kwatra et al., 1993). Activation of transfected tachykinin receptors in CHO cells can also result in the generation of cAMP (Nakajima et al., 1992 Wiener, 1993). 

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