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)

Hemolymph (blood) of an insect, the tobacco hornworm, Manduca sexta, contains a phospholipase A1. The specificity of this enzyme was demonstrated by the use of substrates with labeled fatty acids in specific positions and by conversion of the enzyme product, a lysophospholipid, to 2-acylglycerol by the action of bacterial phospholipase C. The insect phospholipase A1 hydrolyzes phosphatidylethanolamine and phosphatidylglycerol, but not phosphatidylcholine or triolein. Divalent cation is required, with calcium ion being most effective, although strontium, barium, and magnesium ions also support activity. Only substrates dispersed in buffer from ethanol are hydrolyzed; ether, Triton X-100, and taurodeoxycholate are inhibitory. The enzyme has been purified 90-fold. At that stage, it is still far from homogeneous, but stability problems have hindered further purification. It has an apparent Mr = 155,000 +/- 11,000, estimated by gel permeation chromatography.
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PMID:A phospholipase A1 from the hemolymph of the tobacco hornworm, Manduca sexta. 683 59

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

EDTA-insensitive phospholipase A activity hydrolyzing phosphatidylinositol was detected in a bovine brain soluble fraction. This phospholipase A was purified 25-fold by sequential chromatographies of DEAE-Toyopearl, Phenyl-Toyopearl, and Ultrahydrogel 1000. The partially purified EDTA-insensitive phospholipase A showed an apparent molecular mass of 230kDa on an Ultrahydrogel 1000 column in the presence of 0.05% Triton X-100 and a pH optimum at 7.0. The enzyme was highly specific for phosphatidylinositol; phosphatidylethanolamine and phosphatidylcholine were not hydrolyzed significantly. The enzyme activity was characterized as phospholipase A1, and Ca2+ and Mg2+ were not required for its activity. These results indicate the existence of Ca(2+)-independent, phosphatidylinositol-specific metabolism besides those catalyzed by Ca(2+)-dependent phospholipase A2 and Ca(2+)-dependent, phosphatidylinositol-specific phospholipase C.
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PMID:The presence of Ca(2+)-independent phospholipase A1 highly specific for phosphatidylinositol in bovine brain. 821 58

Incubation of [2-3H]glycerol-labeled phosphatidylinositol with a crude cytosol fraction of rat brain in the presence of EDTA yielded [3H]lysophosphatidylinositol predominantly without accumulation of labeled monoacylglycerol and diacylglycerol. The pH optimum of this phospholipase A activity was 8.0. The activity for phosphatidylinositol was twofold higher than for phosphatidylethanolamine, whereas phosphatidylcholine, phosphatidylserine, and phosphatidic acid were not hydrolyzed significantly under the conditions used. The phospholipase A activity for phosphatidylethanolamine was resolved in part from that for phosphatidylinositol by ammonium sulfate fractionation of the cytosol, indicating the existence of at least two forms of EDTA-insensitive phospholipase A. The positional specificity of the phosphatidylinositol-hydrolyzing activity was found to be that of a phospholipase A1, as radioactive lysophosphatidylinositol was produced from 1-stearoyl-2-[1-14C]arachidonyl-sn-glycero-3-phosphoinositol without release of free arachidonate. A phospholipase C activity specific for lysophosphoinositides was found in a membrane fraction from rat brain, which was similar to that characterized in porcine platelets. The phospholipase C was demonstrated to hydrolyze the 2-acyl isomer as well as the 1-acyl isomer of lysophosphatidylinositol. Taken together, our results suggest a possible pathway through which phosphatidylinositol is selectively degraded to the 2-acyl isomer of lysophosphatidylinositol in a Ca(2+)-independent manner, and subsequently converted to a 2-monoacylglycerol in rat brain.
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PMID:A possible pathway of phosphoinositide metabolism through EDTA-insensitive phospholipase A1 followed by lysophosphoinositide-specific phospholipase C in rat brain. 822

Infection of human cells with poliovirus leads to modification of phospholipase activity. Phospholipase C, which generates inositol triphosphate, is stimulated, whereas the activation of phospholipase A2 by the calcium ionophore A23187 is inhibited. Analysis of phospholipid moieties in media of HeLa cells infected with poliovirus indicates that the release of fatty acids is not enhanced during infection, suggesting that phospholipase A1 and A2 activities are not stimulated. The release of choline into the medium is significantly higher 3 h after infection, indicating that a phospholipase that has phosphatidylcholine as its substrate becomes activated. This activation requires viral gene expression because inhibitors of poliovirus gene expression added at the beginning of infection block choline release, but continuous viral protein synthesis is not required. Choline and phosphorylcholine are released into the medium, but the pools of both are gradually depleted in poliovirus-infected cells, perhaps as a consequence of their release into the medium and the increased synthesis of phospholipids that takes place in poliovirus-infected cells. Inhibitors of phospholipase activity such as mepacrine, zinc or cadmium ions significantly reduce this increased release of choline from poliovirus-infected cells. Labelling of cells with [3H]phosphatidylcholine suggests that the choline released from infected cells comes, at least in part, from the hydrolysis of this compound. These results indicate that, in addition to the activation of the phospholipase C which hydrolyses phosphatidylinositol in poliovirus-infected cells, a phospholipase C that acts on a phosphatidylcholine is also activated.
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PMID:Enhancement of phospholipase activity during poliovirus infection. 838 98

The aim of the present paper was to clarify if the prostaglandin F2 alpha (PGF2 alpha) production stimulated by mammalian gonadotropin-releasing hormone (mGnRH) comes from arachidonic acid (AA) freed by diacylglycerol (DAG) and/or membrane phospholipids in the interrenal of Rana esculenta. Interrenals of Rana esculenta were incubated with inhibitors of phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase C (PLC), protein kinase C (PKC) and diacylglycerol lipase (DAGlipase) in the presence or absence of mGnRH. In parallel, the same experiments were carried out using [3H]AA-labelled interrenals. The results of the experiments with non-labelled and [3H]AA-labelled interrenals were in agreement. PLA1, PLA2, PLC, PKC and DAGlipase inhibitors induced a decrease in PGF2 alpha production in interrenals without mGnRH, and PLA2 inhibitor was more effective than other inhibitors. PLC and DAGlipase inhibitors decreased the PGF2 alpha production by interrenals incubated with mGnRH, and PLC inhibitor was more effective than DAGlipase inhibitor. These findings suggest that the main source of AA used for mGnRH-induced PGF2 alpha synthesis is DAG; probably this decapeptide increases PGF2 alpha production enhancing the DAGlipase activity.
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PMID:Mammalian gonadotropin-releasing hormone increases PGF2 alpha production activating diacylglycerol lipase in Rana esculenta interrenal. 845 54

The effect of omega 3 fatty acids on the metabolism of the normal liver was studied using 31P NMR spectroscopy. Human subjects were examined before and after 1, 3 and 7 days of supplementation with 50 mL fish oil per day (12 g omega 3 fatty acids). 31P NMR spectra (1.6 T) revealed a significant increase in phosphodiester (PDE) to ATP ratios after 1 and 3 days of fish oil. After 7 days, [PDE]/[ATP] ratios at a TR of 1 s had returned to baseline levels, but [PDE]/[ATP] at a TR of 5 s appeared to remain high. Rats were fed diets containing 50% of the energy from fish oil or normal rat chow (controls) for 14 days. 31P NMR liver spectra in vivo (4.7 T) confirmed increased [PDE]/[ATP] in rats fed fish oil compared to controls, although the difference was only statistically significant at a TR of 1.5 s but not at a TR of 8 s. 31P NMR spectra of rat liver extracts (8.7 T) suggested that increased concentrations of glycerophosphocholine and possibly glycerophosphoethanolamine were responsible for rising PDE levels in vivo. Phosphocholine (PC) concentrations were markedly reduced in rat liver after fish oil. The combined rise in glycerophosphocholine and reduction in PC would be consistent with a shift from the phospholipase C to the phospholipase A1/A2 pathway of phosphatidylcholine breakdown after fish oil consumption.
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PMID:Effects of fish oil on phospholipid metabolism in human and rat liver studied by 31P NMR spectroscopy in vivo and in vitro. 849 47

A phospholipase C activity highly specific for lysophosphoinositide (lysoPI-PLC) has been demonstrated to be present in synaptic plasma membranes of the rat brain. Several lines of evidence suggested that the lysoPI-PLC is an enzyme distinct from known isoforms of phosphoinositide-specific phospholipase C (PI-PLC). On the other hand, the occurrence of a Ca(2+)-independent phospholipase A1 hydrolyzing PI in rat brain was also demonstrated. The lysoPI-PLC hydrolyzed the 2-acyl isomer as well as the 1-acyl isomer of lysoPI. These findings suggest possible pathways for PI metabolism through lysoPI to yield monoacylglycerol (mainly 2-arachidonoyl glycerol) and inositolphosphates in the brain, which are different from the well-characterized PI-PLC pathway.
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PMID:Phospholipases involved in lysophosphatidylinositol metabolism in rat brain. 890 42

In this work, we have studied the effects and the possible cellular mechanism of Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele crested newt, Triturus carnifex. Adrenals were in vitro superfused with SP, prostaglandin E2 (PGE2), nitric oxide (NO) donor, cyclic GMP (cGMP) analogue, and inhibitors of phospholipase A1, phospholipase A2 (PLA2), phospholipase C, adenylate cyclase (AC), cyclooxygenase (COX), NO synthase (NOS), and soluble guanylate cyclase (sGC). PGE2, corticosterone, and aldosterone release and NOS activity were determined. SP, PGE2, NO donor, and cGMP analogue increased corticosterone and aldosterone; SP and PGE2 increased NOS, and SP increased PGE2. PLA2, AC, COX, NOS, and sGC inhibitors counteracted SP and PGE2 effects, except for PLA2, which did not affect PGE2. These results suggest that SP exhibits a stimulatory role on the corticosteroidogenesis of T. carnifex adrenal gland. In particular SP enhances PLA2 activity, increasing PGE2; this prostaglandin affects AC, which, in turn, enhances NO, and the latter therefore affects sGC, with the consequent corticosteroidogenesis increase.
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PMID:Cellular mechanism of substance P in the regulation of corticosteroid secretion by newt adrenal gland. 914 46

Ehrlich ascites tumor cells, loaded with 3H-labeled arachidonic acid and 14C-labeled stearic acid for two hours, were washed and transferred to either isotonic or hypotonic media containing BSA to scavenge the labeled fatty acids released from the cells. During the first two minutes of hypo-osmotic exposure the rate of 3H-labeled arachidonic acid release is 3.3 times higher than that observed at normal osmolality. Cell swelling also causes an increase in the production of 14C-stearic acid-labeled lysophosphatidylcholine. This indicates that a phospholipase A2 is activated by cell swelling in the Ehrlich cells. Within the same time frame there is no swelling-induced increase in 14C-labeled stearic acid release nor in the synthesis of phosphatidyl 14C-butanol in the presence of 14C-butanol. Furthermore, U7312, an inhibitor of phospholipase C, does not affect the swelling induced release of 14C-labeled arachidonic acid. Taken together these results exclude involvement of phospholipase A1, C and D in the swelling-induced liberation of arachidonic acid. The swelling-induced release of 3H-labeled arachidonic acid from Ehrlich cells as well as the volume regulatory response are inhibited after preincubation with GDP beta S or with AACOCF3, an inhibitor of the 85 kDa, cytosolic phospholipase A2. Based on these results we propose that cell swelling activates a phospholipase A2--perhaps the cytosolic 85 kDa type--by a partly G-protein coupled process, and that this activation is essential for the subsequent volume regulatory response.
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PMID:Cell swelling activates phospholipase A2 in Ehrlich ascites tumor cells. 935 91


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