Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the amount of phospholipids and lysophospholipids of mitochondria and their fragments have been studied under long-term heat incubation. A discrepancy is found between a decrease in the content of phospholipids as a result of their hydrolysis by mitochondrial phospholipase A2 and accumulation of the corresponding lysoderivatives. Data are presented which show that all this is a result of lysoderivatives splitting by lysophospholipase A. The activity of this enzyme is observed in incubation of intact mitochondria, their "ghosts" as well as fractions of the external and internal mitochondrial membranes. It is shown that lysophospholipase A is able to hydrolyze both endogenic and exogenic substrates. The enzyme is active at pH 6.0, lysocardiolipin being the most preferable substrate.
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PMID:[Lysophospholipase activity in mitochondrial membranes of the rat liver]. 323 94

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

Phospholipid catabolism is thought to be one of the critical events in membrane injury during heart ischemia. In this work, the enzymes involved in phospholipid metabolism were studied in purified cultured ventricular myocytes in normoxic and hypoxic conditions. Purified ventricular myocytes exhibited an alkaline phospholipase A activity which had sn-2 specificity and which was calcium dependent, and an acid phospholipase A activity with sn-1 specificity. These cells also exhibited lysophospholipase and acyl-CoA/lysophosphatidylcholine acyltransferase activities. Oxygen deprivation of the myocardial cells for 4 h resulted in a sharp reduction of both phospholipase A2 and A1 activities. The activities of the other lipolytic enzymes were unaffected by hypoxia. Although hypoxia resulted in a marked increase of lactate dehydrogenase leakage in the bathing fluid, no additional release of the lipolytic enzymes and mitochondrial enzyme was observed. However, we noted an important alkaline phospholipase A2 leakage during normoxia. It is suggested that ventricular myocytes, under hypoxia, tend to prevent phospholipid degradation by reducing their phospholipase A activities.
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PMID:Activities of some enzymes of phospholipid metabolism in cultured rat ventricular myocytes in normoxic and hypoxic conditions. 333 66

The phospholipase activity of rat jejunal brush-border membranes was examined in the presence of several solubilizing agents, by measuring the hydrolysis of endogenous membrane phospholipids, as well as the hydrolysis of exogenous, radiolabelled substrates. Enzyme activity was highly stimulated by dispersion in 1% solutions of bile salts, or in a synthetic, bile-salt derivative, 3-[(3-cholamidopropyl)dimethylammonio]propanesulphonate (CHAPS). Under these conditions the endogenous membrane phospholipids were largely degraded to free fatty acids and water-soluble phosphate. In the presence of 1% CHAPS, hydrolysis of exogenous phosphatidylcholine was shown to be due to an initial phospholipase A2-type attack followed by a subsequent lysophospholipase-type attack. These activities co-purified with the brush-border membrane. Maximal phospholipase A2 hydrolysis occurred at an alkaline pH of 8-11, with bile-salt detergents present at greater than their critical micellar concentrations. Hydrolysis was completely divalent-ion independent. Phospholipase A2 activity was not stimulated by 50% diethyl ether or ethanol, or in the presence of 1% solutions of Triton X-100, Zwittergent 3-12, sodium dodecyl sulphate, or n-octylglucoside. Stimulation of phospholipase activity by detergents was not related to their effectiveness at solubilizing the membrane proteins. When assayed individually phosphatidylcholine and lysophosphatidylcholine were each hydrolyzed (at the sn-2 and sn-1 positions, respectively) at a rate of approximately 125 nmol/mg protein per min. When assayed together, the two substrates appeared to compete for the same active site over a wide range of concentrations. It was concluded that the brush-border membrane contains an integral membrane protein with phospholipase A2 and lysophospholipase activities, which is specifically stimulated by bile salts and bile salt-like detergents.
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PMID:Solubilization and assay of phospholipase A2 activity from rat jejunal brush-border membranes. 334 32

Two lysophospholipase activities (designated I and II) were identified in the macrophage-like cell line P388D1. Lysophospholipase I was purified (8,500-fold) to homogeneity by DEAE-Sephacel, Sephadex G-75, Blue-Sepharose, and chromatofocusing chromatography. Lysophospholipase II was separated from the lysophospholipase I in the Blue-Sepharose step. The apparent molecular mass of lysophospholipase I and II are 27,000 and 28,000 daltons, respectively, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Their pI values were 4.4 and 6.1 respectively, as determined by isoelectric focusing. Lysophospholipase I exhibited a broad pH optimum between 7.5-9.0. The double-reciprocal plot of the substrate dependence curve of the purified lysophospholipase I showed a break around the critical micelle concentration of the substrate (1-palmitoyl-sn-glycerol-3-phosphorylcholine). The apparent Km, determined from substrate concentrations above 10 microM was 22 microM, and the apparent Vmax was 1.3 mumol min-1mg-1. The purified enzyme did not have phospholipase A1, phospholipase A2, acyltransferase, or lysophospholipase-transacylase activity. No activity was detected toward triacylglycerol, diacylglycerol, p-nitrophenol acetate, p-nitrophenol palmitate, or cholesterol ester. The enzyme did, however, hydrolyze monoacylglycerol although at a rate 20-fold less than lysophospholipid, 0.06 mumol min-1mg-1. The lysophospholipase I was inhibited by fatty acids but not by glycerol-3-phosphorylcholine, glycerol-3-phosphorylethanolamine, or glyc-fjerol-3-phosphorylserine. A synthetic manoalide analogue 3(cis,cis,-7,10)hexadecadienyl-4-hydroxy-2-butenolide inhibited the enzyme with half-inhibition (IC50) at about 160 microM. Triton X-100 decreased the enzymatic activity, although this apparent inhibition can be explained by a "surface dilution" effect. The pure lysophospholipase I was stable for at least 5 months at -20 degrees C in the presence of glycerol and beta-mercaptoethanol. Lysophospholipid also demonstrated a protective effect during the later stage of purification.
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PMID:Purification and characterization of a lysophospholipase from a macrophage-like cell line P388D1. 338 24

The influence of ischaemia and revascularisation on lipid peroxidation and phospholipid metabolism in the rat small intestinal mucosa was investigated. Two hours of total ischaemia followed by five minutes of revascularisation caused not only accumulation of malondialdehyde in the mucosa, but also increased activity of phospholipase A2, decreased activity of lysophospholipase, and increased ratio between lysophosphatidylcholine and phosphatidylcholine. Pretreatment with the phospholipase A2 inhibitor, quinacrine, prevented the increases in mucosal phospholipase A2 activity and lysophosphatidylcholine/phosphatidylcholine ratio after ischaemia and morphological examinations revealed that the mucosa was then also protected against ischaemic injury. These findings point to the possibility that activation of phospholipase A2 and accumulation of lysophosphoglycerides could be involved in mediating the mucosal injury caused by small intestinal ischaemia.
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PMID:Increased phospholipase A2 and decreased lysophospholipase activity in the small intestinal mucosa after ischaemia and revascularisation. 342 70

Rat platelets released phospholipase A2 and lysophospholipase upon activation with thrombin or ADP. The release of phospholipases was energy-dependent and was not in parallel with that of a known lysosomal marker enzyme, N-acetyl-beta-D-glucosaminidase. The phospholipases are derived from other granules (dense granules or alpha-granules) rather than lysosomal granules of the cells. All of the activities of both phospholipases in the cell free fraction obtained from the activated platelet reaction mixture was recovered in the supernatant after centrifugation at 105,000 X g. The degree of hydrolysis of phospholipids by the phospholipase A2 followed the order: phosphatidylethanolamine (PE) greater than phosphatidylserine (PS) greater than phosphatidylcholine (PC). Phospholipase A2 shows a broad pH optimum (greater than pH 7.0) and absolutely requires Ca2+. Lysophospholipase was specific to lysophosphatidylserine (lysoPS), and neither lysophosphatidylethanolamine (lysoPE) nor lysophosphatidylcholine (lysoPC) was hydrolyzed appreciably. Both 1-acyl- and 2-acyl-lysophosphatidylserine were equally hydrolyzed. Lysophospholipase activity shows similar pH optimum to phospholipase A2. The lysophospholipase activity was lost easily at 60 degrees C. The activity was reduced by the presence of EDTA, though low but distinct activity was observed even in the presence of EDTA. Addition of Ca2+ to the mixtures restores the full activity.
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PMID:Selective release of phospholipase A2 and lysophosphatidylserine-specific lysophospholipase from rat platelets. 357 Dec 10

The developmental profiles of the protective mechanisms of heart against peroxidative injury during neonatal growth was examined in the pigs of three different age groups. Lipid peroxidation expressed in terms of malonaldehyde formation was considerably higher in the pig hearts of the 8-10 day age group compared to that either by newborn or adult age groups. The four principal antioxidative enzymes, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase (G6PD), were enhanced during early neonatal growth and, with the exception of G6PD, all other enzymes were further enhanced during further growth to adulthood. G6PD activity dropped significantly in adult heart. The phospholipid contents of myocardial membrane between newborn and week-old pigs did not vary significantly. Total phospholipids and phosphatidylcholine contents were significantly higher in adult heart compared to those in neonatal heart. The enzymes of phospholipid synthesis and degradation, fatty acyl CoA synthetase (FACS), phospholipase A2 (PLA2), lysophospholipase (LPL), and lysophophatidylcholine acyltransferase (LPCAT) increased during early neonatal growth. During further growth to adulthood, FACS decreased, PLA2 did not change, whereas both LPL and LPCAT increased significantly. Analysis of free fatty acids showed that palmitic and stearic acids decreased during the first week of growth, but increased during further growth to adulthood. Oleic acid did not change with aging, but arachidonic acid dropped in adult heart compared to that in neonatal heart. Linoleic, palmitoleic and free fatty acids increased dramatically during the first week of neonatal growth, but dropped thereafter. These results suggest that the unusual peroxidative status of the week-old pig heart is related to the presence of high concentrations of polyunsaturated fatty acids in the membrane phospholipids and not with the antioxidative defense system.
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PMID:Developmental profiles of protective mechanisms of heart against peroxidative injury. 359 80

It was found that phospholipase A2 and lysophospholipase, both of which were released from thrombin-stimulated rat platelets, had high affinity to insolubilized heparin. Phospholipase A2 released from rat platelets was purified by the sequential use of column chromatography on heparin-Sepharose and TSK gel G2000SW (high-performance liquid chromatography, HPLC). The enzyme was near homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and HPLC, and its Mr was estimated to be 13,500. The purified enzyme was labile and lost its activity within 1 h when incubated at 37 degrees C. Phospholipids or detergent in the solution protected the enzyme against inactivation. Phospholipase activity was inhibited by p-bromophenacylbromide, but not by diisopropylfluorophosphate or iodoacetamide. Lysophospholipase, which was also released from rat platelets, was separated from phospholipase A2 by chromatography on heparin-Sepharose.
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PMID:Purification and characterization of phospholipase A2 released from rat platelets. 359 43

Highly purified chromaffin granule membranes contain high levels (100 nmol/mg protein) of long-chain free fatty acids (Husebye, E.S. and Flatmark, T. (1984) J. Biol. Chem. 259, 15272-15276), as well as lysophosphatidylcholine (268 nmol/mg protein) and lysophosphatidylethanolamine (92 nmol/mg protein). The release of saturated and unsaturated long-chain fatty acids from endogenous phospholipids was 38 and 28 nmol/mg protein per h, respectively, at 37 degrees C and pH 7.5 (alkaline pH optimum). p-Bromophenacyl bromide inhibited the release of palmitate and oleate by 88 and 65%, respectively. The deacylation of membrane phospholipids was not significantly affected by micromolar free Ca2+. Based on experiments with pancreatic phospholipase A2, stearate and arachidonate were found to be suitable markers for deacylation at the sn-1 and sn-2 positions, respectively. Experiments with exogenously added labeled phosphatidylcholines confirmed that chromaffin granule ghosts contain a phospholipase A2 activity (alkaline pH optimum). The preparations also revealed a phospholipase A1 activity (acid pH optimum). Finally, the ghosts contain a lysophospholipase activity (alkaline pH optimum), that accounts for the major part of the deacylation of membrane phospholipids, notably the release of saturated fatty acids (stearate and palmitate). It is unlikely that the high content of lysophospholipids is an artifact of the procedure by which the granule ghosts are isolated.
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PMID:Characterization of phospholipase activities in chromaffin granule ghosts isolated from the bovine adrenal medulla. 360 74


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