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. The composition and metabolism of phospholipids were studied in various tissues from both normal and dystrophic mice of the 129 ReJ strain. Phospholipids extracted from forebrain, spinal cord, sciatic nerve and plasma were fractionated by t.l.c. and measured. 2. Very significant alterations were found in the choline phospholipids from these tissues, except forebrain. Plasma phosphatidylcholine in the dystrophic mouse was increased by 38%. There was a 2-fold increase in lysophosphatidylcholine in the spinal cord of dystrophic mice. The sciatic nerve showed a marked decrease in sphingomyelin content, which is approximately half of that in the controls. 3. Five enzymes involved in phosphatidylcholine metabolism [namely cholinephosphotransferase (EC 2.7.8.2); phospholipases A (EC 3.1.1.4, EC 3.1.1.32); lysophospholipase (EC 3.1.1.5); lysophosphatidylcholine acyltransferase (EC 2.3.1.23); phospholipase C (EC 3.1.4.3)] were studied in tissue preparations from forebrain, spinal cord, sciatic nerves, gastrocnemius muscles and liver. 4. Activities of phospholipases A and C were significantly increased, about 5-fold and 60% respectively, in gastrocnemius muscle of dystrophic mice compared with controls. Phospholipases A also showed 50% higher activity in the sciatic nerves of dystrophic than of normal mice. Lysophosphatidylcholine acyltransferase activities were significantly increased in the sciatic nerves and spinal cord, by 50-100% over that of the controls. The forebrain and spinal cord from dystrophic mice, however, had only 60% of lysophospholipase activities of that of the normal control. Cholinephosphotransferase activity was unchanged in these tissues from both normal and dystrophic mice. 5. It is suggested that are number of features of mouse muscular dystrophy related to altered membrane structure and function can be rationalized in terms of changes in lipid composition and metabolism.
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PMID:Phospholipid composition and metabolism in mouse muscular dystrophy. 72 3

Human preimplantation embryos and endometrium secrete platelet-activating factor (PAF). The mechanism of phosphatidylcholine (PC) degradation stimulated by PAF was investigated in endometrial explants prelabeled with [methyl-3H]choline or preincubated with [3H]butan-1-ol. Analysis of the water-soluble metabolites of PAF-induced PC hydrolysis in secretory endometrium demonstrated that the stimulated generation of [3H]choline ([3H]Cho) precedes that of [3H]choline phosphate ([3H]ChoP) and [3H]glycerophosphocholine ([3H]GPC). Within 30 sec there was a rapid rise in PAF-induced [3H]Cho generation and by 2 min this had increased to 59.9% +/- 10.6% (p less than 0.02), with no effect upon [3H]ChoP and [3H]GPC during this period. Both [3H]GPC and [3H]ChoP, however, were increased at a later time point. The slower [3H]ChoP generation may suggest that PC-specific phospholipase C activation as well as delayed [3H]GPC rise may be due to PC-specific phospholipase A2 and lysophospholipase activation. Phospholipase D activity was confirmed by the incorporation of high-specific-activity [3H]butan-1-ol into [3H]phosphatidylbutanol ([3H]PBut). The rapid generation of [3H]PBut, which paralleled the rise in intracellular [3H]Cho, strongly suggests that PC breakdown is catalyzed by the phospholipase D pathway. It is proposed that PAF induces PC hydrolysis as a consequence of an early phospholipase D-catalyzed breakdown of PC in human secretory endometrium. This may be an alternative source for prostaglandin synthesis and an important pathway essential for long-term activation of local cellular events at the time of implantation.
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PMID:Platelet-activating factor mediates phosphatidylcholine hydrolysis by phospholipase D in human endometrium. 163 48

Thirty and 60-min ischemic insults resulted in an increase in free fatty acid and 1,2- diacylglycerol contents of rat forebrain. No significant changes were detected in phospholipids except phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate during ischemic insult. Phosphatidylinositol 4-monohosphate and phosphatidylinositol 4,5-bisphosphate contents decreased during ischemia. Although the increase in free fatty acid contents continued, 1,2-diacylglycerol did not show further increase after 30-min ischemia. These results suggest that there may be another pathway for the accumulation of free fatty acids in addition to phospholipase C coupled to di- and monoacylglycerol lipase. Free fatty acid and 1,2-diacylglycerol contents increased transiently and thereafter decreased to control levels within 90 min after postischemic recirculation. The decrease in arachidonic acid content preceded those of other FFA. Phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate contents gradually increased after the initiation of recirculation in ischemic brains. Lysophosphatidylcholine decreased gradually after temporary increase during 15 and 5-min recirculations in 30 and 60-min ischemic groups. Phospholipase A, phospholipase C, and di- and monoacylglycerol lipase activities did not show significant changes during entire course of recirculation. Total activities of lysophospholipase and acylation enzymes of lysophospholipid demonstrated 1.5-and 2.2-fold increase during 30-min recirculation.
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PMID:Changes in lipid metabolites and enzymes in rat brain due to ischemia and recirculation. 191 Mar 56

Endogenous free choline levels and acetylcholine (ACh) synthesis in nerve terminals were investigated using cerebral cortical synaptosomes of C57BL/6 mice. Endogenous choline was produced at a rate ten-fold faster than ACh to provide levels adequate for the formation of the latter. The combined pool size of the water-soluble intermediates derived from phosphatidylcholine (PhC), such as glycerophosphorylcholine (GpCh) and phosphorylcholine (PCh), increased significantly during the first 10-15 min of incubation and was always higher than that of free choline. These results most likely indicate an effective degradation of PhC by the combined action of phospholipase A2/lysophospholipase, as well as by phospholipase C in synaptosomes. ACh synthesis proceeded at a constant rate in the presence or absence of exogenous free choline (0-10 microM) and was almost entirely abolished in the presence of 10(-6) M hemicholinium-3. These results suggest that ACh is effectively synthesized by free choline generated in synaptosomes by a coupling mechanism involving the high-affinity choline uptake system. No changes in the production rates of choline and ACh were observed between adult and aged mice.
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PMID:Phospholipid-derived choline intermediates and acetylcholine synthesis in mouse brain synaptosomes. 258 48

Ischemic rat brains were prepared by decapitation followed by incubation in an artificial cerebrospinal fluid at various times at 37 degrees C, and the levels of phospholipids, free fatty acids, and enzymes involved in their metabolism were studied. Activities of phospholipase A, phospholipase C, and di- and monoglyceride lipase, assayed with optimal concentrations of Ca2+ and lysophospholipase, did not significantly change by 60 min of ischemia, whereas acylation enzymes of lysophospholipid decreased in activity to an extent of 70% of control at 15 min after the ischemic treatment. The maximal activities were found at 8 x 10(-3)M, 1 x 10(-3) M, and 2 x 10(-2) M Ca2+ for phospholipase A, phospholipase C, and di- and monoglyceride lipases, respectively in microsomal fractions of both control and ischemic brain. Furthermore, the sensitivity of microsomal enzymes to endogenous Ca2+ was estimated in control and ischemic brain. The sensitivity of phospholipase C was found to be increased after 1 min of ischemic treatment, but those of phospholipase A and di- and monoglyceride lipase were not increased.
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PMID:Activities of enzymes metabolizing phospholipids in rat cerebral ischemia. 274 39

We have investigated the effects of the specific platelet-activating factor (PAF; 1-alkyl-2-acetyl-glycerophosphocholine) antagonist BN52021 on free fatty acid (FFA) and diacylglycerol (DG) accumulation and on the loss of fatty acids from phosphatidylinositol-4,5-bisphosphate (PIP2) in mouse brain. Mice were pretreated with BN52021 (10 mg/kg, i.p.) 30 min before electroconvulsive shock (ECS) or postdecapitation ischemia. These procedures cause rapid breakdown of PIP2 and accumulation of FFA and DG. Lipid extracts were prepared from microwave-fixed cerebrum and fractionated by TLC, and the fatty acid methyl esters were prepared by methanolysis and quantified by capillary GLC. In saline or vehicle (dimethyl sulfoxide)-treated mice, ECS caused marked accumulation of FFA and DG and loss of mainly stearic (18:0) and arachidonic (20:4) acids from PIP2. BN52021 pretreatment of ECS-treated mice decreased the accumulation of free palmitic (16:0), 18:0, 20:4, and docosahexaenoic (22:6) acids with no effect on the fatty acids in DG or the loss of PIP2. BN52021 had no effect on basal levels of FFA, DG, or PIP2. One minute of postdecapitation ischemia induced PIP2 loss and accumulation of FFA and DG. BN52021 attenuated the accumulation of free 20:4 and 22:6 acids, decreased the content of oleic (18:1), 20:4, and 22:6 acids in DG, but had no effect on PIP2 loss. These data indicate that BN52021 reduces the injury-induced activation of phospholipase A2 and lysophospholipase, which mediate the accumulation of FFA in brain, while having a negligible effect on phospholipase C-mediated degradation of PIP2.
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PMID:Platelet-activating factor antagonist BN52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock. 284 88

Thrombin-induced changes in arachidonate content of platelet phospholipids were quantitated to establish the ultimate origins of this eicosanoid precursor. Fifteen seconds following thrombin addition (15 U/5 X 10(9) platelets), phosphatidylcholine lost 11.8 nmol of arachidonate and phosphatidylethanolamine lost 10.5 nmol. Arachidonate in phosphatidate, phosphatidylinositol, and phosphatidylinositol-4,5-bisphosphate combined decreased by 11.0 nmol. Increases in free and oxygenated arachidonate (41 nmol) exceeded decreases in inositides. Thus phospholipase A2 released at least twice as much arachidonate as phospholipase C-diglyceride lipase. Phosphatidylinositol-4-phosphate levels remained unchanged upon stimulation. Therefore, increases in phosphatidylinositol-4,5-bisphosphate indicated the minimum rate of phosphorylation of phosphatidylinositol to resynthesize phosphatidylinositol-4,5-bisphosphate, following stimulus-induced breakdown by phospholipase C. Phosphatidylinositol-4, 5-bisphosphate increased 1.4 nmol between 10 and 15 sec following thrombin, markedly less than phosphatidylinositol decreased (2.1 nmol). This could be due to phospholipase A2, in addition to phospholipase C, acting directly on phosphatidylinositol to a greater extent than estimated by accumulation of lysophosphatidylinositol, degraded rapidly by lysophospholipase. Thus, upon high-dose thrombin stimulation of human platelets inositide metabolism via phospholipase C directs initial formation of intracellular second messengers, and sequentially, or in parallel, arachidonate release by phospholipase A2 supplies the larger proportion of arachidonate for syntheses of eicosanoids involved in intercellular communication.
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PMID:Stimulated platelets release equivalent amounts of arachidonate from phosphatidylcholine, phosphatidylethanolamine, and inositides. 302 86

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


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