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)

Phospholipase activity in the lysosomes of the protozoan Tetrahymena pyriformis strain NT-1 was studied using phospholipids radioactively labeled in the fatty acid moieties. Lysosomal homogenates showed high phospholipase activity with an acidic pH optimum. Unlike the phospholipases in rat liver lysosomes, almost all activity was recovered from the membranous fraction of the lysosomes. The activity was partially solubilized by treatment of the membranes with a detergent or trypsin. Using specifically labeled phospholipids revealed that phospholipase. A1 and C are predominant in Tetrahymena lysosomes, no appreciable phospholipase A2 or lysophospholipase activity was detected in the fraction. There are two catabolic pathways of the hydrolysis of phospholipid: Hydrolysis is initiated by deacylation at the 1-position by phospholipase A1 and the 2-acyllysophospholipid thus formed is successively attacked by (lyso)phospholipase C; hydrolysis is initiated by cleavage of phosphodiester by phospholipase C and the diacylglycerol thus formed is attacked by lipase. Both pathways give the same end products, free fatty acid and 2-monoacylglycerol. The former pathway might be predominant in Tetrahymena lysosomes under physiological conditions since the pathway is independent of detergent. Phospholipases A1 and C activities were partially released into the medium. At least two different phospholipases C are present in the medium as judged by chromatographic behavior and their substrate specificities.
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PMID:Properties of acid phospholipases in lysosome and extracellular medium of Tetrahymena pyriformis. 308 63

The pathways for degradation of phosphatidylinositol (PI) were investigated in sonicated suspensions prepared from confluent cultures of bovine pulmonary artery endothelial cells. The time courses of formation of 3H-labeled and 14C-labeled metabolites of phosphatidyl-[3H]inositol ([3H]Ins-PI) and 1-stearoyl-2-[14C] arachidonoyl-PI were determined at 37 degrees C and pH 7.5 in the presence of 2 mM EDTA with or without a 2 mM excess of Ca2+. The rates of formation of lysophosphatidyl-[3H]inositol ([3H]Ins-lyso-PI) and 1-lyso-2-[14C] arachidonoyl-PI were similar in the presence and absence of Ca2+, and the absolute amounts of the two radiolabeled lyso-PI products formed were nearly identical. This indicated that lyso-PI was formed by phospholipase A1, and phospholipase A2 was not measurable. In the presence of EDTA, [14C]arachidonic acid release from 1-stearoyl-2-[14C]arachidonoyl-PI paralleled release of glycerophospho-[3H]inositol ([3H]GPI) from [3H]Ins-PI. Formation of [3H]GPI was inhibited by treatment with the specific sulfhydryl reagent, 2,2'-dithiodipyridine, and this was accompanied by an increase in [3H]Ins-lyso-PI. In the presence of Ca2+, [14C] arachidonic acid release from 1-stearoyl-2-[14C]arachidonoyl-PI was increased 2-fold and was associated with Ca2+-dependent phospholipase C activity. Under these conditions, [3H]inositol monophosphate production exceeded formation of [14C]arachidonic acid-labeled phospholipase C products, diacylglycerol plus monoacylglycerol, by an amount that was equal to the amount of [14C]arachidonic acid formed in excess of [3H]GPI. Low concentrations of phenylmethanesulfonyl fluoride (15-125 microM) inhibited Ca2+-dependent [14C]arachidonic acid release, and the decrease in [14C] arachidonic acid formed was matched by an equivalent increase in 14C label in diacylglycerol plus monoacyclglycerol. These data supported the existence of two pathways for arachidonic acid release from PI in endothelial cells; a phospholipase A1-lysophospholipase pathway that was Ca2+-independent and a phospholipase C-diacylglycerol lipase pathway that was Ca2+-dependent. The mean percentage of arachidonic acid released from PI via the phospholipase C-diacylglycerol lipase pathway in the presence of Ca2+ was 65 +/- 8%. The mean percentage of nonpolar phospholipase C products of PI metabolized via the diacylglycerol lipase pathway to free arachidonic acid was 28 +/- 3%.
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PMID:Ca2+-dependent and Ca2+-independent pathways for release of arachidonic acid from phosphatidylinositol in endothelial cells. 311 76

The myocardium contains diverse cellular components and heterogeneous phospholipid-containing membranes. The major phospholipids are phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositnol, sphingomyelin and cardiolipin. The phospholipases capable of hydrolyzing these membrane lipids include phospholipase A, lysophospholipase, and phosphatidylnositol-specific phospholipase C. Early studies revealed that myocardial phospholipase A with an acid pH is localized to lysosomes; those with more alkaline and neutral activities are present in cytosol, microsomes, mitochondria and sarcolemma. Recently, we have identified phosphatidylinositol-specific phospholipase C activity in bovine myocardium with molecular weights ranging from 40,000 to 271,000. Interestingly, forms I, II and III, had pH optima ranging from 4.5 to 5.5; form III also had significant activity at pH 7.0. All activities were stimulated by calcium, suggesting that they are different from calcium-independent phospholipases C found in liver and brain. The pathophysiological significance of these four cytosolic forms of phospholipase C remains to be determined. Thus, under injury-promoting conditions, phospholipase C appears capable of hydrolyzing membrane-associated phosphatidylinositol and the polyphosphoinositides, whereas phospholipases A and lysophospholiphases appear to prefer non-inositol containing phospholipids. Finally, very recent studies suggest "free radical-triggered lipolysis" by phospholipases as a possible mechanism for production of lysophospholipids in myocardial membranes.
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PMID:Phospholipases of the myocardium. 331 Sep 98

Human liver was homogenised and fractionated by differential centrifugation, and the subcellular fractions were characterised biochemically. Absolute values and distribution patterns of protein and marker enzyme activities obtained from human liver have also been compared with those from rat liver. In addition, acid phospholipase activities have been studied in human liver. On the basis of product formation from stereo-specifically radiolabeled phosphatidylethanolamine substrates, lysosomal phospholipases A1 and A2 with optimal activities at pH 4.7 have been identified in human liver. Acid phospholipase C and lysophospholipase activities, however, were not found in human liver. Cationic amphiphilic drugs inhibited the activities of the acid phospholipases A in human and rat liver lysosomes to about the same extent.
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PMID:Fractionation, biochemical characterization and lysosomal phospholipases of human liver. 358 66

The murine macrophage (M phi) cell line, P388D1, was employed as a source of M phi phospholipases in order to characterize the enzymatic properties and subcellular localization of these enzymes because of their importance for prostaglandin biosynthesis. Phospholipase activity was assessed with dipalmitoylphosphatidylcholine (DPPC) as substrate. Phospholipases were characterized with respect to divalent cation dependence, pH optima, and localization in subcellular compartments using linear sucrose gradients. By these criteria a number of different phospholipases were identified. Most importantly, a single Ca2+-dependent activity with a pH optimum of 8.8 was identified in membrane-rich fractions (plasma membrane, mitochondria, and endoplasmic reticulum) and could be clearly separated from the remaining activities, which are Ca2+ independent and exhibit pH optima of 7.5, 5.1, and 4.2. The phospholipases with acidic pH optima may be associated with subcellular components containing lysosomal enzymes and both phospholipase A1 and phospholipase A2 activities are observed. In contrast, the phospholipase activity with a pH optimum of 7.5 sediments with the cytosolic proteins and is inhibited by 5 mM Ca2+. No significant phospholipase C activity was detected in assays performed with or without added Ca2+ at pH's 4.2, 5.1, 7.5, or 8.8 using DPPC as substrate. However, the P388D1 cells do contain a lysophospholipase that is at least 20 times more active than the phospholipase A activities identified. Its presence must be taken into account in evaluating the positional specificities and properties of the macrophage phospholipases.
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PMID:Phospholipase activities of the P388D1 macrophage-like cell line. 398 20

It has been well recognized that acyl groups of phospholipids play an important role for structure and function of biomembrane. The turnover of these acyl groups in normal brain biomembrane is also well known. Some types of enzymic system related to this turnover has been investigated. Phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase belong to these enzymic systems. In this report, the sequential changes of phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase activities in ischemic rat brain were examined. The purpose of this study was to examine the enzymic changes of deacylation-reacylation cycle of biomembrane phospholipid in ischemic brain. Ischemic brain were produced by decapitation and activities of 5 enzymes were assayed in microsomal fraction. The activities of phospholipase A, PI-specific phospholipase C, lipase showed high value during early stage of ischemia for 15 or 30 min and then decreased gradually. Lysophospholipase activity was not changed for 120 min. On the other hand, acylCoA: lysophospholipid acyltransferase activity showed gradual decrease from the beginning of ischemia. There are some reports that in early ischemic stage, the concent of free fatty acids increase, while that of phospholipid decrease. The present results may suggest that the changes of free fatty acid and phospholipid in ischemic brain are related to these enzymic system.
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PMID:[The activities of phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase in ischemic brain microsomal fraction]. 402 86

Hydrolysis of 2-[1-14C]oleoyl phosphatidylcholine and of 1-[1-14C]oleoyl lysophosphatidylcholine by lysosomes prepared from rat liver using Triton WR-1339 has been studied. At pH 5.0 sodium taurocholate stimulated the release by the soluble lysosomal fraction of labelled lysophosphatidylcholine, diacyl- and monoacylglycerol and fatty acids from [14C]phosphatidylcholine. The time course of appearance of labelled products suggested that monoacylglycerol could be released as a result of the action of phospholipase A1 followed by lysophospholipase C or by the initial action of phospholipase C followed by monoacylglycerol lipase. The hydrolysis of 1-[14C]acyl lysophosphatidylcholine was also stimulated by sodium taurocholate under similar conditions; however, only release of monoacylglycerol was increased, whereas release of fatty acid was inhibited. Mg2+ inhibited the release of labelled monoacylglycerol and of fatty acid from lysophosphatidylcholine. The detergents deoxycholate and Triton X-100 and phospholipids were strongly inhibitory. 5'-AMP almost completely suppressed release of monoacylglycerol but increased release of fatty acid. Chloroquine strongly suppressed release of monoacylglycerol and only at high concentration (1.25 mM) diminished fatty acid release. In the presence of sodium taurocholate the predominant mechanism for degradation of phosphatidylcholine by the soluble fraction of lysosomes involves phospholipase A followed by phospholipase C. Assay of release of monoacylglycerol from [14C]lysophosphatidylcholine catalyzed by extracts of fibroblasts from patients with Niemann-Pick disease and controls in the presence of taurocholate revealed that lysophospholipase C activity was lacking in those cell lines that were deficient in sphingomyelinase. This suggests that lysophospholipase C and sphingomyelinase activities may be catalyzed by one enzyme.
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PMID:Degradation of lysophosphatidylcholine by lysosomes. Stimulation of lysophospholipase C by taurocholate and deficiency in Niemann-Pick fibroblasts. 673 21

Lysosomal catabolism of radioactively labelled phosphatidylethanolamine, phosphatidylcholine and several potential metabolites of these diacylphospholipids was studied using rat-liver lysosomes which had been isolated from Triton WR-1339-treated animals. Hydrolysis of these lipids seems to be restricted to the soluble lysosomal compartment. The initial intralysosomal degradation is predominantly catalysed by phospholipase A1 (EC 3.1.1.32) followed by lysophospholipase (EC 3.1.1.5). The end products of this pathway are free fatty acids and glycerophosphorylethanolamine or glycerophosphorylcholine. These phosphodiesters are not hydrolysed further in lysosomes, as has been shown previously (Fowler, S. and De Duve, C. (1969) J. Biol. Chem. 144, 471-481). The intermediary lysophospholipids, however, are also hydrolysed by an alternative pathway, i.e. by a lysophospholipase which catalyses the hydrolysis of the glycerophosphate ester bond, followed by a monoacylglycerol lipase and a phosphomonoesterase (EC 3.1.3.2), respectively. Besides these two catabolic routes of intralysosomal hydrolysis of phosphatidylethanolamine and phosphatidylcholine, additional pathways are possible, which seem, however, to be of minor importance, at least in the substrate concentration ranges employed in these studies. These additional reactions include attack by a phospholipase A2 (EC 3.1.1.4) and--as discovered recently (Matsuzawa, Y. and Hostetler, K.Y. (1980) J. Biol. Chem. 255, 646-652)--by a phospholipase C (EC 3.1.4.3). Cations such as Mg2+, Ca2+, K+ and Na+ inhibit preferentially deacylation reactions.
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PMID:Hydrolytic degradation of phosphatidylethanolamine and phosphatidylcholine by isolated rat-liver lysosomes. 706 64

Venoms from two related Australian ants, a jumper ant (Myrmecia pilosula) and a bulldog ant (Myrmecia pyriformis), were quantitatively analysed for the following enzymic activities: phospholipase A2, phospholipase B, phospholipase C, hyaluronidase, esterase, acid phosphatase, alkaline phosphatase and phosphodiesterase. Both venoms contained phospholipase A2, phospholipase B, hyaluronidase, acid phosphatase and alkaline phosphatase activities. Myrmecia pyriformis venom had significantly greater phospholipase B, acid phosphatase and alkaline phosphatase activities than Myrmecia pilosula venom. No detectable quantities of phospholipase C, esterase or phosphodiesterase activities were found in either venom.
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PMID:Some enzymic activities of two Australian ant venoms: a jumper ant Myrmecia pilosula and a bulldog ant Myrmecia pyriformis. 772 23

A phospholipase activity has been associated with the interaction of Rickettsia prowazekii with the surface of erythrocytes and competent host cells as well as during the growth of the rickettsiae within their host cells. Both fatty acid and lysophosphatides have been found in the interaction of rickettsiae with the surface of eucaryotic cells; this finding provided strong evidence for the activity of a phospholipase A. However, fatty acids, but not lysophosphatides, were found during the growth of rickettsiae within cells in which the phospholipids had been radiolabeled with oleic acid; this observation left the type of phospholipase activity in doubt. In this study, the water-soluble components of phospholipid hydrolysis by phospholipase A plus lysophospholipase and phospholipase C were determined following the growth of rickettsiae in host cells in which the phospholipids had been radiolabeled with choline. In infected cells relative to mock-infected cells, there was a loss of phosphatidylcholine with a corresponding increase not in lysophosphatidylcholine but in the water-soluble components. There was a large increase in glycerylphosphorylcholine (185%) and a smaller increase in phosphorylcholine (16%). These results indicate that both phospholipase A activity (plus a lysophospholipase activity) and phospholipase C were increased during infection by R. prowazekii and that the former was the predominant activity.
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PMID:Analysis of hydrolytic products from choline-labeled host cell phospholipids during growth of Rickettsia prowazekii. 813 53


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