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:3.1.1.5 (neuropathy target esterase)
1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The distribution of the hydrolyses of phosphatidylcholine by phospholipase A2 and phospholipase A1, and the hydrolysis of lysophosphatidylcholine by lysophospholipase, in subcellular and subsynaptosomal fractions of cerebral cortices of guinea-pig brain, was determined. 2. Noradrenaline stimulated hydrolysis by phospholipase A2 in whole synaptosomes, synaptic membranes and fractions containing synaptic vesicles. 3. Stimulation of hydrolysis by phospholipase A2 in synaptic membranes by noradrenaline was enhanced by CaCl2, and by a mixture of ATP and MgCl2. The optimum concentration of CaCl2, in the presence of ATP and MgCl2, for stimulation by 10 muM-noradrenaline was in the range 1-10muM. The optimum concentration for ATP-2MgCl2 in the presence of 1 muM-CaCl2 was in the range 0.1-1mM. 4. Hydrolysis by phospholipase A2 of synaptic membranes was also stimulated by acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine), histamine, psi-aminobutyric acid, glutamic acid and aspartic acid. With appropriate concentrations of cofactors, sigmoidal dose-response curves were obtained, half-maximum stimulations being obtained with concentrations of stimulant in the range 0.1-1muM. 5. Taurine also stimulated hydrolysis of phosphatidylcholine by phospholipase A2. There were only slight stimulations with methylamine, ethylenediamine or spermidine. No stimulation was obtained with glucagon.
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PMID:The stimulation by transmitter substances and putative transmitter substances of the net activity of phospholipase A2 of synaptic membranes of cortex of guinea-pig brain. 19 82

We have recently characterized lysophospholipase A2 activities in guinea-pig heart microsomes and postulated that these enzymes act sequentially with phospholipases A1 to release fatty acids selectively from phosphatidylcholine (PC) and phosphatidylethanolamine, thus providing an alternative route to the phospholipase A2 mode of release. In a further investigation of the postulated pathway, we have characterized the PC-hydrolysing phospholipase A1 in guinea-pig heart microsomes. Our results show that the enzyme may have a preference for substrates with C16:0 over C18:0 at the sn-1 position. In addition, although the enzyme cleaves the sn-1 fatty acid, the rate of hydrolysis of PC substrates with C16:0 at the sn-1 position was influenced by the nature of the fatty acid at the sn-2 position. The order of decreasing preference was C18:2 > C20:4 = C18:1 > C16:0. The hydrolyses of the molecular species were differentially affected by heating at 60 degrees C. An investigation into the effect of nucleotides on the activity of the enzyme showed that guanosine 5'-[gamma-thio]triphosphate (GTP[S]) inhibited the hydrolysis of PC by phospholipase A1 activity, whereas GTP, guanosine 5'-[beta-thio]diphosphate (GDP[S]), GDP, ATP and adenosine 5'-[gamma-thio]triphosphate (ATP[S]) did not affect the activity. The inhibitory effect of GTP[S] on phospholipase A1 activity was blocked by preincubation with GDP[S]. A differential effect of GTP[S] on the hydrolysis of different molecular species was also observed. Taken together, the results of this study suggest the presence of more than one phospholipase A1 in the microsomes with different substrate specificities, which act sequentially with lysophospholipase A2 to release linoleic or arachidonic acid selectively from PC under resting conditions. Upon stimulation and activation of the G-protein, the release of fatty acids would be inhibited.
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PMID:Evidence for the regulation of guinea-pig heart microsomal phosphatidylcholine-hydrolysing phospholipase A1 by guanosine 5'-[gamma-thio]triphosphate. 147 9

Incubation of bovine rod outer segments (ROS) with radiolabeled palmitic acid (16:0) and lysophosphatidylcholines (lysoPC) radiolabeled in either the fatty acid or the choline group indicated the presence of a lysophospholipase activity that is unaffected by Ca2+. In the presence of ATP, Mg2+ and CoA and acyl CoA:lysophospholipid acytransferase activity is evident, and free fatty acids, including those released by lysophospholipase activity, are esterified to membrane phospholipids. At low concentrations of lysoPC, 68% of it is acylated to form phosphatidylcholine (PC) and 24% is converted to glycerophosphocholine (GPC) and fatty acid per hour. As the concentration of lysoPC increases lysophospholipase activity increases, acyl-CoA:lysophospholipid acyltransferase activity decreases, and the proportion of lysoPC converted to PC decreases. The rate of production of lysophospholipids in vitro under phospholipase A-stimulatory conditions exceeds the rate at which it can be removed by 5-10-fold. This suggests the possibility that an early step in light, anoxia- or hypoxia-induced damage to photoreceptor cells may be activation of the phospholipase A endogenous to ROS.
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PMID:Lysophospholipase and the metabolism of lysophosphatidylcholine in isolated bovine rod outer segments. 292 Jul 84

Phospholipase B from a fungus Penicillium notatum, which was previously shown to possess phospholipase B activity as well as lysophospholipase activity, was found to have another activity to convert lysophospholipid to phospholipid, to an extent comparable to its phospholipase B activity. The enzyme did not incorporate free fatty acid into phospholipid in the presence of CoA and ATP. The results shown here coincide with data reported on yeast phospholipase B and may imply the functional and structural kinship between two related enzymes.
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PMID:Lysophosphatidylcholine----phosphatidylcholine converting activity of Penicillium notatum phospholipase B. 339 Jan 93

Incubation of intact platelets from Sinclair(S-1) miniature swine with 32P-labeled lysophosphatidylcholine (lyso PC) indicated the presence of an active lysophospholipase with a pH optimum of 8.0 for hydrolysis of the substrate. However, lyso PC was incorporated into the membrane phosphatidylcholines by the acyltransferase pathway upon addition of ATP, Mg++ and CoA to the platelet suspension. These results suggest that intact platelets are able to resist the cytotoxic effects of lyso PC in plasma, and the phospholipids in platelet membranes are not readily affected by the lipid environment of the plasma. The acyltransfer reaction apparently is saturated with endogenous free fatty acids since arachidonic acid added exogenously did not further enhance the incorporation activity. Neither the acyltransferase nor the lysophospholipase activity was affected by Ca++, but divalent metal ions such as Zn++ inhibited the lysophospholipase activity. Cholesterol but not cholesteryl esters elicited a biphasic effect on both enzymes, stimulating at low concentration but inhibiting at a cholesterol to lyso PC ratio greater than 1. Serum albumin inhibited the lysophospholipase but gave a small biphasic effect to the acyltransferase.
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PMID:Metabolism of lysophosphatidylcholine by swine platelets. 399 May 21

Exposure of isolated arteries to oxidatively modified low density lipoprotein (LDL) has been reported to suppress endothelium-dependent relaxation (EDR). To determine whether lipid degradation products in oxidized LDL contribute to impaired relaxation, we have tested the responsiveness of isolated rabbit aortas to endothelium-dependent relaxants (acetylcholine, ATP, and calcium ionophore A23187) and nitroglycerin before and after 2-hour incubations with selected lipids and LDL preparations. Concentrations (10 microM) of lecithin, phosphatidylserine, lysophosphatidylserine, sphingomyelin, phosphatidic acid, palmitate, arachidonate, and auto-oxidized arachidonate had no effect on EDR. Concentrations (10 microM) of lysolecithin, lyso-platelet activating factor, and sphingosine significantly suppressed endothelium-dependent relaxation. Native LDL (100 micrograms/ml incubation buffer) containing only small amounts of lysophosphatidylcholine exerted no effect on EDR. In contrast, LDL preparations oxidatively modified by exposure to cultured endothelial cells or copper inhibited EDR. When modified LDL was depleted of its lysolecithin by treatment with a selective phospholipase B (lysolecithinase), the inhibitory effects were attenuated. In contrast, native LDL accumulating lysolecithin under the influence of a phospholipase A2 (lecithinase) exerted inhibitory effects mimicking those of oxidized LDL. Lipids and lipoproteins had no effect on the responsiveness to nitroglycerin, an endothelium-independent vasodilator. We conclude that lysolecithin in oxidatively modified LDL contributes importantly to its vasomotor effects.
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PMID:Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. 841 38

It has been known since ancient times that turtle hearts exhibit extraordinary tolerance to anoxia or ischemia. The mechanisms by which they accomplish this remain obscure. The most important adaptation in anoxic turtles is a rapid and dramatic decrease in metabolic rate. Nuclear magnetic resonance measurements indicate that painted turtle (Chrysemys picta) hearts respond to anoxia with a rapid decrease in phosphocreatine (PCr; to 50% of control) after which PCr remains constant for at least 4 h. ATP is defended and does not decrease while intracellular pH (pHi) decreases by 0.2 pH units early in anoxia and is then maintained constant. Softshelled turtles (Trionyx spinifer) have been demonstrated to be far more sensitive than painted turtles to anoxia in vivo. However, isolated hearts from softshelled turtles appear to be as anoxia tolerant as those of Chrysemys. During ischemia there is also little difference in cardic performance, high energy phosphates, or pHi between these two species. A peculiar feature of turtle hearts is an extremely high concentration of phosphodiesters (PDE). The role of cytosolic PDEs remains controversial but they may function as lysophospholipase inhibitors and thereby limit phospholipid turnover (Burt CT and Ribolow H, Comparative Biochemistry and Physiology, 108B: 11-20, 1994). Whether PDEs promote anoxia/ischemia tolerance is unknown but these stresses can result in membrane lipid dysfunction in mammals. Metabolic control, acid-base, and phospholipid homeostasis all play a role in anoxia and ischemia tolerance in turtle hearts. These physiologic processes are interdependent, and how they interact in these animals is unknown, but they are experimentally accessible by modern analytical methods.
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PMID:Anoxia and ischemia tolerance in turtle hearts. 872 53

A CHO cell-derived 80-kDa recombinant polypeptide (GenBank number I15470I15470) putatively encoding a calcium-independent phospholipase A2 was expressed in S. frugiperda cells resulting in over a 15-fold increase in a calcium-independent phospholipase A1/A2 activity which was entirely inhibitable by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one. The recombinant polypeptide was purified from cytosol by sequential tandem affinity chromatographies employing ATP-agarose and calmodulin-Sepharose stationary phases. This strategy resulted in the rapid purification (36 h) of recombinant phospholipase A2 activity in 56% overall yield to a single intense 80-kDa protein band on SDS-polyacrylamide gel electrophoresis after silver staining. The purified protein possessed phospholipase A1, phospholipase A2, and lysophospholipase activities. Microbore anion exchange chromatography demonstrated that the 80-kDa protein band was comprised of multiple distinct isoforms including an anionic isoform which possessed over a 5-fold higher specific activity (5 micromol/mg.min) than earlier eluting isoforms. Collectively, these results unambiguously demonstrate that: 1) the 80-kDa polypeptide catalyzes phospholipase A1/A2 and lysophospholipase activities with distinct kinetic parameters; 2) calmodulin and ATP both interact with the catalytic polypeptide independent of regulatory proteins; and 3) distinct isoforms of this polypeptide exist which possess markedly different specific activities.
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PMID:Expression, purification, and kinetic characterization of a recombinant 80-kDa intracellular calcium-independent phospholipase A2. 894 72

A Ca2+-independent phospholipase A2 (PLA2) maximally active at pH 4 and specifically inhibited by the transition-state analogue 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33) was isolated from rat lungs. The sequence for three internal peptides (35 amino acids) was used to identify a 1653-base pair cDNA clone (HA0683) from a human myeloblast cell line. The deduced protein sequence of 224 amino acids contained a putative motif (GXSXG) for the catalytic site of a serine hydrolase, but showed no significant homology to known phospholipases. Translation of mRNA produced from this clone in both a wheat germ system and Xenopus oocytes showed expression of PLA2 activity with properties similar to the rat lung enzyme. Apparent kinetic constants for PLA2 with dipalmitoylphosphatidylcholine as substrate were Km = 0.25 mM and Vmax = 1.89 nmol/h. Activity with alkyl ether phosphatidylcholine as substrate was decreased significantly compared with diacylphosphatidylcholine. Significant lysophospholipase, phospholipase A1, or 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase activity was not observed. Enzyme activity was insensitive to p-bromophenacyl bromide, bromoenol lactone, trifluoromethylarachidonoyl ketone, mercaptoethanol, and ATP, but was inhibited by MJ33 and diethyl p-nitrophenyl phosphate, a serine protease inhibitor. SDS-polyacrylamide gel electrophoresis with autoradiography of the translated [35S]methionine-labeled protein confirmed a molecular mass of 25.8 kDa, in good agreement with the enzyme isolated from rat lung. By Northern blot analysis, mRNA corresponding to this clone was present in both rat lung and isolated rat granular pneumocytes. These results represent the first molecular cloning of a cDNA for the lysosomal type Ca2+-independent phospholipase A2 group of enzymes.
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PMID:Identification of a human cDNA clone for lysosomal type Ca2+-independent phospholipase A2 and properties of the expressed protein. 899 71

We previously reported that platelets release a soluble factor that decreases the solute permeability of cultured bovine aortic endothelial monolayers. This factor was characterized as heat stable, tryspsin sensitive, and not serotonin, adenosine, ADP, or ATP [F. R. Haselton and J. S. Alexander. Am. J. Physiol. 263 (Lung Cell Mol. Physiol. 7): L670-L678, 1992]. We now report its identity as lysophosphatidic acid (LPA). Endothelial permeability decreases rapidly, reversibly, and repeatedly when exposed to platelet supernatants. Continuous exposure produces a sustained decrease in permeability. Methanol extracts of platelet supernatants also decrease endothelial permeability. Treatment of methanol extracts of platelet supernatants with phospholipase B or alkaline phosphatase, which modify the structure of LPA, abolishes the permeability-decreasing activity. However, activity is unaffected by treatment with phospholipase A2. This pattern of enzyme inactivation is consistent with the structure of LPA. Furthermore, synthetic 1-oleoyl-LPA rapidly and significantly decreases endothelial permeability in a concentration-dependent manner. Platelet activation does not appear to be required to produce activity in supernatants from platelet isolations, since P-selectin expression is not increased and thromboxane B2 is < 14 pg/6,000 platelets. Our data show that platelets release a methanol-extractable compound with an enzyme degradation profile consistent with LPA, which decreases the permeability of endothelial monolayers in vitro. In vivo, LPA derived from platelets may be an important mediator of the transport barrier formed by the vascular endothelium.
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PMID:Platelet-derived lysophosphatidic acid decreases endothelial permeability in vitro. 945 59


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