Phosphatidylinositol phospholipase

Hydrolytic cleavage by phosphatidylinositol phospholipase C (PI-PLC) of the cyclic myo-inositol-l,2-phosphate (cIP) at C-2 is faster than that at C-1. A cyclic monofluorophosphonate has been prepared as a stable analogue of the substrate in... 

Postulated transition state analogue Figure 7.63 Inhibition of phosphatidylinositol phospholipase C. 

Pettitt, T.R., Martin, A., Horton, T., Liossis, C, Lord, J.M., and Wakelam M.J.O., 1997, Diacyl-glycerol and phosphatidate generated by phospholipases C and D, respectively, have distinct fatty add compositions and functions. J. Biol. Chem. 272 17354 17359 Powis G., Seewald, M.J., Gratas, C., Melder, D., Riebow, J., and Modest, E.J., 1992, Selective inhibition of phosphatidylinositol phospholipase C by cytotoxic ether lipid analogs. Cancer Res. 52 2835-2840... 

Helsper, J.P.F.G., Heemskerk, J.W.M. and Veerkamp, J.H., 1987, Cytosolic and particulate phosphatidylinositol phospholipase C activity in pollen of Lilium longiflorum. Physiol. Plant. 71 120-126. 

Chiarini, A., Fiorilli, A., Siniscalco, C., Tettamanti, G., and Venerando, V., 1990, Solubilization of the membrane-bound sialidase from pig brain by treatment with bacterial phosphatidylinositol phospholipase C, J. Neurochem. 55 1576-1584. 

Phosphatidic acid is glycerol esterified at the sn-1 and sn-2 positions to two fatty acids and at the sn-3 position to phosphoric acid. It is a product of phospholipase D action that is also an intermediate in the biosynthesis of phosphatidylseiine and phosphatidylinositol. 

Hormonal factors and other stimuli by activating phospholipase C-(3 or -y isoforms stimulate the breakdown of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol, a reaction called PI response. 

Covalent regulation. Following occupation and activation of the M2 acetyl choline receptors, phospholipase C (PLC), is activated and both inositol (l,4,5)-trisphosphate (IP3), and diacylglycerol (DAG), are formed by hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2). 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

The mechanisms involved in platelet activation are discussed in Chapter 51 (see Figure 51-8). The process involves interaction of the stimulus (eg, thrombin) with a receptor, activation of G proteins, stimulation of phospholipase C, and hberation from phosphatidylinositol... 

Figure 4 Schematic representation of the Ca2+-transporting systems affecting cellular calcium homeostasis during hormonal stimulation, oq = oq-adrenergic receptor VP = vasopressin receptor PLC = phospholipase C PI = phosphatidylinositol PIP = phospha-tidylinositol-4-phosphate PIP2 = phosphatidylinositol-4,5-biphosphate IP3 = inositol-1,4,5-triphosphate DG = diacylglycerol PKC = protein kinase C. (Modified from Refs. 125 and 285.)...

Inositol triphosphate (IP3)-gated channels are also associated with membrane-bound receptors for hormones and neurotransmitters. In this case, binding of a given substance to its receptor causes activation of another membrane-bound protein, phospholipase C. This enzyme promotes hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3. The IP3 then diffuses to the sarcoplasmic reticulum and opens its calcium channels to release Ca++ ions from this intracellular storage site. 

Zaikova, T. (2001). Synthesis of fluorogenic substrates for continuous assay of phosphatidylinositol-specific phospholipase C. Bioconjug. Chem. 12, 307-313. 

A bacterial phosphatidylinositol specific phospholipase C (PI-PLC) had been available for many years before it was demonstrated to strip a number of membrane-bound proteins from eukaryotic cell surfaces [1], Such proteins are anchored by a PI moiety in which the 6 position of inositol is glycosidically linked to glucosamine, which in turn is bonded to a polymannan backbone (Fig. 3-10). The polysaccharide chain is joined to the carboxyl terminal of the anchored protein via amide linkage to ethanolamine phosphate. The presence of a free NH2 group in the glucosamine residue makes the structure labile to nitrous acid. Bacterial PI-PLC hydrolyzes the bond between DAG and phosphati-dylinositols, releasing the water-soluble protein polysac charide-inositol phosphate moiety. These proteins are tethered by glycosylphosphatidylinositol (GPI) anchors. 

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. 

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