Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Lysosomes from rat liver contain two enzymic systems for hydrolysing phosphatidyl-inositol: a deacylation via lysophosphatidylinositol producing glycerophosphoinositol and non-esterified fatty acid, and a phospholipase C-like cleavage into inositol 1-phosphate and diaclygycerol. 2. The separate enzyme systems involved can be distinguished by gel filtration, differential temperature-stability and the inhibitory action of detergents. 3. The enzyme systems both have pH optima at 4.8 and their attack on a pure phosphatidylinositol substrate is inhibited by many bivalent metals including Ca2+ and Mg2+, and cationic drugs. 4. Whereas the deacylation system will attack other glycerophospholipids, the phospholipase C shows a marked specificity towards phosphatidylinositol, although it will also slowly attach phosphatidylcholine with the liberation of phosphocholine. 5. Gel filtration and temperature-stability distinguish the phospholipase C from lysosomal phosphatidic acid phosphatase, but not from sphingomyelinase. 6. Evidence is presented that an EDTA-insensitive phospholipase C degrading phosphatidylinositol is present in rat brain.
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PMID:The hydrolysis of phosphatidylinositol by lysosomal enzymes of rat liver and brain. 74 53

A phospholipase C prepared from lymphocytes readily hydrolysed pure phosphatidyl-inositol but was relatively ineffective against phosphatidylinositol in erythrocyte "ghosts" and rat liver microsomal fraction and also against sonicated lipid extracts from these membranes. In contrast, a phospholipase C prepared from Staphylcoccus aureus readily hydrolysed phosphatidylinositol in sonicated lipid extracts but had only low activity against purified phosphatidylinositol. Unlike the enzyme from lymphocytes, the S. aureus phospholipase C did not require Ca2+ for its activity and was inhibited by cations. The previously reported specificity of this enzyme was confirmed by our observation of hydrolysis of approx. 75% of the phosphatidylinositol in ox, sheep and cat erythrocyte "ghosts" together with no detectable effect on the major erythrocyte membrane phospholipids. The phosphatidylinositol of rat liver microsomal fraction was hydrolysed only to a maximum of 15%. Some preliminary experiments showed that approx. 60% of the phosphatidylinositol of ox or sheep erythrocytes could be hydrolysed without causing substantial haemolysis.
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PMID:The action of phosphatidylinositol-specific phospholipases C on membranes. 127 8

The effect of various detergents on polyphosphoinositide-specific phospholipase C activity in highly purified wheat root plasma membrane vesicles was examined. The plasma membrane-bound enzyme was solubilized in octylglucoside and purified 25-fold by hydroxylapatite and ion-exchange chromatography. The purified enzyme catalyzed the hydrolysis of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) with specific activities of 5 and 10 mumol/min per mg protein, respectively. Phosphatidylinositol (PI) was not a substrate. Optimum activity was between pH 6-7 (PIP) and pH 6-6.5 (PIP2). The enzyme was dependent on micromolar concentrations of Ca2+ for activity, and millimolar Mg2+ further increased the activity. Other divalent cations (4 mM Ca2+, Mn2+ and Co2+) inhibited (PIP2 as substrate) or enhanced (PIP as substrate) phospholipase C activity.
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PMID:Polyphosphoinositide phospholipase C in wheat root plasma membranes. Partial purification and characterization. 131 Aug 75

Phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus thuringiensis (0.11 units per ml) inhibited growth of IC-Sofia carcinoma cell line in culture by 64%. The growth of transplanted carcinoma in hamsters was also inhibited by 29% at a dose of 4.9 units of PIPLC/kg animal/day. In addition, degeneration processes and a significant fibrosis of the tumour occurred. The functional, clinical, biochemical and haematological parameters studied were consistent with the established antitumour effect in vivo.
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PMID:Effect of phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis on solid spinocellular carcinoma. 131 7

[3H]Inositol ([3H]Ins) labeling of phosphoinositides was studied in rat brain cortical membranes. [3H]Ins was incorporated into a common lipid pool through both CMP-dependent and independent mechanisms. These are as follows: (1) a reverse reaction catalyzed by phosphatidyl-inositol (PtdIns) synthase, and (2) the reaction performed by the PtdIns headgroup exchange enzyme, respectively. Membrane phosphoinositides prelabeled in either CMP-dependent or independent fashions were hydrolyzed by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)- and carbachol-stimulated phospholipase C. Unlike CMP-dependent labeling, however, CMP-independent incorporation of [3H]Ins into lipids was inhibited by 1 mM (0.04%) sodium deoxycholate. Thus, when PtdIns labeling and phospholipase C stimulation were studied in a concerted fashion, [3H]Ins was incorporated into lipids primarily through the PtdIns synthase-catalyzed reaction because of the presence of deoxycholate required to observe carbachol-stimulation of phospholipase C. Little direct breakdown of [3H]PtdIns was detected because production of myo-[3H]inositol 1-monophosphate was minimal and myo-[3H]inositol 1,4-bisphosphate was the predominant product. Although PtdIns labeling and 3H-polyphosphoinositide formation were unaffected by GTP gamma S and carbachol and had no or little lag period, GTP gamma S- and carbachol-stimulated appearance of 3H-Ins phosphates exhibited an appreciable lag (10 min). Also, flux of label from [3H]Ins to 3H-Ins phosphates was restricted to a narrow range of free calcium concentrations (10-300 nM). These results show the concerted activities of PtdIns synthase, PtdIns 4-kinase, and phospholipase C, and constitute a simple assay for guanine nucleotide-dependent agonist stimulation of phospholipase C in a brain membrane system using [3H]Ins as labeled precursor.
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PMID:Concerted CMP-dependent [3H]inositol labeling of phosphoinositides and agonist activation of phospholipase C in rat brain cortical membranes. 131 77

An ectoenzyme hydrolyzing diadenosine polyphosphates (ApnA) to AMP and Ap(n-1) has been studied in cultured chromaffin cells from bovine adrenal medulla. The KM value for extracellular Ap4A hydrolysis was 2.90 +/- 0.72 microM, the V(max) value obtained was 11.59 +/- 0.92 pmol/min x 10(6) cells (116 pmol/min.mg total protein). Ap3A, Ap5A, Ap6A, and Gp4G were competitive inhibitors of Ap4A hydrolysis with K(i) values of 3.65, 1.10, 1.20, and 2.65 microM, respectively. Phosphatidylinositol-specific phospholipase C removes the ApnA hydrolase activity from cultured chromaffin cells, suggesting an anchorage of this protein to the plasma membrane through the phosphatidylinositol. The turnover time for this enzyme calculated in the presence of cycloheximide was 38.94 +/- 1.53 hr for cultured chromaffin cells.
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PMID:Extracellular hydrolysis of diadenosine polyphosphates, ApnA, by bovine chromaffin cells in culture. 132 12

Profilin was originally discovered in a tight complex with monomeric actin from bovine spleen, leading to its description as an actin monomer sequestering protein that maintains a pool of unpolymerized actin in cells. Subsequent purifications of profilin using different methods from diverse cells have consistently yielded preparations that affect the kinetics of actin assembly but do not efficiently maintain actin monomeric at steady state in solutions containing mM magnesium. Recent evidence that profilin inhibits phospholipase C and enhances nucleotide exchange of actin has led some to question whether profilin is ever truly an actin monomer sequestering agent. Here we report that the extraction of bovine spleen with fluoride- and pyrophosphate-containing solutions facilitates isolation of monomeric actin that is bound to profilin and does not polymerize in mM magnesium ion. The integrity of this complex depends on the presence of ATP. Phosphatidylinositol 4-monophosphate (PIP), previously shown to dissociate the low-affinity profilin-actin complex (Kd = 0.4 microM in mM Mg2+), also dissociates the high-affinity profilin-actin complex (Kd less than 0.02 microM in mM Mg2+) yielding actin that is polymerization competent and profilin that functions like profilins purified by conventional methods. Although the chemical basis of these results is not known, they indicate that profilin can tightly sequester actin monomers and support the earlier suggestion that the affinity of profilin for actin may be under metabolic control.
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PMID:Isolation of the phosphatidylinositol 4-monophosphate dissociable high-affinity profilin-actin complex. 132 1

We investigated the turnover of polyphosphoinositides in bovine retinal microvascular endothelial cells and rat astrocytes cultured in the presence of high ambient concentrations of glucose in order to study the possible involvement of this pathway in the pathogenesis of diabetic retinopathy. a 35-45% decrease in the amount of 32P incorporated into phosphatidylinositol(4)phosphate (PIP) and phosphatidyl-inositol(4,5)biphosphate (PIP2) occurred in rat astrocytes but not bovine retinal endothelial cells grown for 14 +/- 3 days in a medium with an elevated (28 mM) glucose concentration. Incorporation of 32P into phosphatidylinositol, phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine was not altered by these conditions. A 39-45% decrease in 32P incorporated into PIP/PIP2 was also found in rat astrocytes grown in 28 mM glucose which were detergent solubilized and incubated with [32P]ATP. Exposure to elevated concentrations of glucose decreased the amount of PIP/PIP2 cleaved by ionomycin or fluoroaluminate treatment, but did not disturb phospholipase C activity. Thus, the lower level of PIP/PIP2, induced by exposure to elevated concentrations of glucose, appears due to changes in phospholipid substrate levels, or polyphosphoinositide kinase activity, rather than a decrease in ATP levels or phospholipase C activity. These results suggest that high ambient glucose levels alter second-messenger generation by astrocytes. In turn, cellular interactions dependent upon these second messengers and important for maintenance of normal microvessel function in the retina may be disrupted.
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PMID:Effect of elevated ambient glucose upon polyphosphoinositide turnover in bovine retinal endothelial cells and rat astrocytes. 132 21

Phosphatidylinositol-specific phospholipase C (PtdIns-PLC) of Bacillus cereus catalyzes the conversion of PtdIns to inositol cyclic 1:2-phosphate and diacylglycerol. NIH 3T3, Swiss mouse 3T3, CV-1, and Cos-7 cells were transfected with a cDNA encoding this enzyme, and the metabolic and cellular consequences were investigated. Overexpression of PtdIns-PLC enzyme activity was associated with elevated levels of inositol cyclic 1:2-phosphate (2.5-70-fold), inositol 1-phosphate (2-20-fold), and inositol 2-phosphate (3-20-fold). The increases correlated with the levels of enzyme expression obtained in each cell type. The turnover of phosphatidylinositol (PtdIns) was also increased in transfected CV-1 cells by 13-fold 20 h after transfection. The levels of PtdIns, phosphatidic acid, diacylglycerol, or other inositol phosphates were not detectably altered. Expression of bacterial PtdIns-PLC decreased rapidly after 20 h implying that either the increased PtdIns turnover or the accumulation of inositol phosphates was detrimental to cells and that by some adaptive mechanism enzyme expression was suppressed.
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PMID:Mammalian cells that express Bacillus cereus phosphatidylinositol-specific phospholipase C have increased levels of inositol cyclic 1:2-phosphate, inositol 1-phosphate, and inositol 2-phosphate. 132 86

Phosphatidylinositol (PtdIns) kinase and phosphatidylinositol 4-phosphate (PtdIns4P) kinase have been studied in a purified sarcolemmal fraction isolated from rat heart. Both enzymes were Mg(2+)-dependent and their activities were maximal at 2.5 mM Mg2+ and pH 7.5. Kinetic analysis of endogenous substrate phosphorylation by ATP showed that the apparent Km and Vmax values for PtdIns kinase were 292 +/- 17 microM and 1390 +/- 80 pmol.mg-1.min-1, respectively, while the apparent Km and Vmax values for PtdIns4P kinase were 398 +/- 25 microM and 382 +/- 24 pmol.mg-1.min-1. Under normal conditions, the activity of PtdIns4P kinase was lower than that of PtdIns kinase; however, the former activity increased several fold in the presence of PtdIns4P as an exogenous substrate. The enzymatic synthesis of intramembranal PtdIns4P and phosphatidylinositol 4,5-bisphosphate (PtdIns (4,5)P2) was maximally enhanced by 0.1% Triton X-100 and inhibited by micromolar concentrations of Ca2+. Inhibition of PtdIns and PtdIns4P kinase showed IC50 values for Ca2+ of 20 and 6 microM, respectively, and was independent of either Ca(2+)-induced activation of phospholipase C and polyphosphoinositide monophosphoesterases or low ATP concentrations. The results indicate that purified rat heart sarcolemmal membranes contain a very active phosphoinositide phosphorylation system which is regulated by micromolar levels of Ca2+. The Ca2+ effect may contribute to the feedback inhibition of the receptor-activated formation of inositol 1,4,5-trisphosphate.
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PMID:Phosphoinositide kinases in rat heart sarcolemma: biochemical properties and regulation by calcium. 133 11


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