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)

Cells of Mycoplasma mycoides var. Capri grown in a medium containing 10 micrograms/ml cholesterol (native organisms) or in cholesterol-free medium (adapted organisms) were treated with phospholipase A2. Hydrolysis of polar lipids (phosphatidylglycerol and diphosphatidylglycerol) only occurred in the adapted cells. Cholesterol replenishment of the membranes of these adapted cells in vitro which involves an increase from 7 micrograms to 66 micrograms cholesterol/mg membrane protein, completely abolished hydrolysis of polar lipid pools by phospholipase A2. This suggests that cholesterol incorporated either during growth or under conditions in vitro has an identical disposition and function in the membrane. This observation further indicates that cholesterol incorporation in M. mycoides var. Capri can be explained in terms of a simple physical adsorption process. Polar-lipid breakdown products resulting from phospholipase A2 action on intact cells, isolated membranes and lipids extracted from adapted organisms were analyzed. In experiments with intact cells [14C]oleic lysoderivatives but not [3H]palmitic lysoderivatives are accumulated within the membranes. In membrane preparations, again only [14C]oleic lysoderivatives are accumulated but transiently. Finally, both [14C]oleic and [3H]palmitic lysoderivatives were produced in phosphatidylglycerol-diphosphatidylglycerol liposomal preparations. From these results it can be concluded that: (a) 80% of the phosphatidylglycerol and diphosphatidylglycerol have an unusual positional distribution of their fatty acid (unsaturated oleic acid in position 1) and (b) membranes of M. mycoides var. Capri contain an active lysophospholipase which more efficiently hydrolyzes palmitic-acid-containing lysoderivatives.
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PMID:Effect of membrane cholesterol on action of phospholipase A2 in Mycoplasma mycoides var. Capri. Evidence for lysophospholipase activity. 700 48

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

Two lysophospholipases were isolated from the venom of an Australian elapid snake (subfamily Acanthophiinae), Pseudechis australis, by sequential chromatography on CM-52 cellulose, Sephadex G-75 and DE-52 cellulose columns. They were very similar to each other. One of them, lysophospholipase I, was obtained as a homodimer, the monomer of which consisted of 123 amino acid residues with seven disulphide bridges. The amino acid composition and the N-terminal amino acid sequence of the enzyme were similar to those of phospholipase A2, Ca2+ was required for its activity and the maximum activity was attained at 2 mM-CaCl2 in the presence of 1 mM-EDTA. The optimum pH was 7.5. Lysophospholipase I hydrolysed lysophosphatidylcholine more rapidly than lysophosphatidylethanolamine. It did not hydrolyse, however, phosphatidylcholine, 1-palmitoylglycerol, tripalmitoylglycerol or p-nitrophenyl acetate. Modification of the enzyme with p-bromophenacyl bromide or 2-nitrophenylsulphenyl chloride suppressed the activity. A strong direct haemolytic activity was exhibited when the lysophospholipase was present together with phospholipase A2.
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PMID:Isolation and properties of lysophospholipases from the venom of an Australian elapid snake, Pseudechis australis. 710 39

Two lipolytic enzymes--phospholipase A2 and lysophospholipase A1 were isolated in individual state from the venom of the big hornet Vespa orientalis. It was shown that these enzymes have approximately the same molecular weight of about 26 000, but differ in their electrophoretic mobilities. Besides, the enzymes possess marked specificity to lecithin and L-lysolecithin, respectively.
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PMID:[Isolation and purification of two lipolytic enzymes from Vespa orientalis venom]. 727 51

Several lipolytic enzymes from guinea-pig pancreas have been determined in a soluble extract and in a purified zymogen granule fractions. The positional specificity of phospholipolytic enzymes was detected using phospholipids bearing various radioactive labels. It is shown that guinea-pig pancreatic extracts are able to release both fatty acids from phosphatidylcholine, but with more efficiency towards the fatty acid occupying the 1-position of sn-glycerol. Evidence is given that guinea-pig pancreas lacks the classical secretory phospholipase A2 and that phospholipid digestion is achieved through the sequential action of phospholipase A1 and lysophospholipase.
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PMID:Evidence for the lack of classical secretory phospholipase A2 in guinea-pig pancreas. 729 66

A phospholipase A2 bound tightly to the particulate fractions of rat ascites hepatoma cells was purified approximately 13,000-fold with a reasonably high yield (34%) by extraction with sodium cholate, ammonium sulfate fractionation, solubilization with sodium dodecyl sulfate, column chromatographies on Sephadex G-150 in the presence of sodium dodecyl sulfate, and on DEAE-cellulose and CM-cellulose in the presence of Triton X-100. The enzyme has a unique substrate specificity; namely, it preferentially hydrolyzes phosphatidylethanolamine and, to a lesser degree, phosphatidylglycerol. However, it does not attack phosphatidylcholine, phosphatidic acid or cardiolipin in the present experimental conditions. The final preparation shows both phospholipase A2 and lysophospholipase L2 activities, but neither lysophospholipase L1 nor lipase activity. The purified enzyme has a rather broad pH optimum ranging from 7 to 9, requires Ca2+, and is resistant to heat-treatment at 95 degree C for 5 min.
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PMID:Purification and properties of a membrane-bound phospholipase A2 from rat ascites hepatoma 108A cells. 739 Sep 73

An "A1 type" phospholipase activity with serine-phospholipid preference was released by rat activated platelets. It was distinct from the secretory type II phospholipase A2 [Horigome, K., Hayakawa, M., Inoue, K., and Nojima, S. (1987) J. Biochem. 101, 625-631] and co-purified with the secretory lysophosphatidylserine-selective lysophospholipase activity [Higashi, S., Kobayashi, T., Kudo, I., and Inoue, K. (1988) J. Biochem. 103, 442-447]. Several lines of evidence indicated that a single protein was responsible for the phospholipase A1 and lysophospholipase activities. Marked accumulation of lysophospholipids was observed in rat calcium ionophore-activated washed platelets and both phospholipase A1/lysophospholipase and type II phospholipase A2 were shown to contribute to this phospholipid degradation. A selective inhibitor of type II phospholipase A2 reduced the phospholipid degradation and enhanced the clotting time and prothrombinase activity. These results indicate that secretory platelet phospholipases may play a role in regulation of blood clotting.
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PMID:Phospholipid degradation in rat calcium ionophore-activated platelets is catalyzed mainly by two discrete secretory phospholipase As. 749 Feb 72

Entamoeba histolytica phospholipase A and lysophospholipase activities from a vesicular subcellular fraction (P30) were analyzed. The products, obtained using specific substrates labeled with 14C or 3H, indicated the presence of phospholipase A1 and A2 as well as lysophospholipase L1 activities. The enzymes detected could participate in phospholipid metabolism and the alkaline phospholipase A2 may contribute to E. histolytica cytopathogenicity.
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PMID:Identification of Entamoeba histolytica intracellular phospholipase A and lysophospholipase L1 activities. 762 91

The regulation of the lysophospholipase activity of the 85-kDa cytosolic phospholipase A2 (PLA2) was studied in vitro and in stimulated macrophages. Bovine serum albumin was found to inhibit lysophospholipase activity of the recombinant 85-kDa PLA2 when assayed at a relatively low substrate concentration. Inhibition could be reversed if the substrate concentration was increased or if Ca2+ was present in the assay. Incubation of recombinant enzyme with macrophage membranes and lipid extracts from macrophage membranes resulted in the release of arachidonic acid, as well as, stearic acid, which is enriched at the sn-1 position of macrophage phospholipids. This suggests that with a bilayer substrate the PLA2 can sequentially deacylate the sn-2 then sn-1 acyl groups. This was verified by demonstrating that the phospholipids, phosphatidylcholine and phosphatidylinositol, were hydrolyzed to glycerophosphocholine and glycerophosphoinositol by incubation with recombinant 85-kDa PLA2. The 85-kDa enzyme was identified as the main lysophospholipase activity in mouse peritoneal macrophage cytosols. Addition of Ca2+ to the assay enhanced activity, but this effect decreased as the substrate concentration was increased. Incubation of macrophages with zymosan increased the lysophospholipase activity of the 85-kDa PLA2 in cytosols. Phosphorylation of recombinant PLA2 with mitogen-activated protein kinase resulted in an increase in lysophospholipase, as well as, PLA2 activity. In macrophages stimulated with zymosan release of stearic acid (18:0) and palmitic acid (16:0) was observed in addition to arachidonic acid (20:4). These results are consistent with a role of the 85-kDa PLA2 in regulating lysophospholipid levels in macrophages during zymosan stimulation.
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PMID:Regulation of lysophospholipase activity of the 85-kDa phospholipase A2 and activation in mouse peritoneal macrophages. 765 19

Clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 were investigated for their effects on FaDu cells, a human squamous carcinoma cell line. These agents, at concentrations within the therapeutic range (0.25-2 micrograms/ml), caused a dose-dependent tumor cell cytotoxicosis which was greatly enhanced in the presence of human neutrophils. The neutrophil-mediated increment in tumoricidal activity, but not the direct antitumor effects of the drugs per se, was inhibited by catalase. The effects of these drugs on three more cell carcinoma lines as well as on two primary cultures and a noncarcinoma cell line were also investigated and compared with the activity of the standard antitumor chemotherapeutic agents bleomycin, cisplatin, and methotrexate. All seven cultures were sensitive to clofazimine and B669 compared to six that were sensitive to cisplatin, three that were sensitive to bleomycin, and one that was sensitive to methotrexate. The treatment of FaDu cells with clofazimine and B669 was associated with enhanced activity of phospholipase A2, as evidenced by increased release of radiolabeled arachidonate and lysophosphatidylcholine from membrane phospholipids. Inhibitors of arachidonic acid metabolism, protein kinase C inhibitors, as well as water and lipid soluble antioxidants failed to protect the cells against the cytotoxic activity of clofazimine and B669. However, alpha-tocopherol, a lysophospholipid-complexing agent, completely blocked the antiproliferative effects of the riminophenazines and also protected the cells against the direct cytotoxic effect of lysophosphatidylcholine, while the lysophospholipid-neutralizing enzyme lysophospholipase protected against the riminophenazines. These observations demonstrate that the tumoricidal properties of clofazimine and B669 are probably due to increases in the lysophospholipid content of cell membranes.
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PMID:The riminophenazine agents clofazimine and B669 inhibit the proliferation of cancer cell lines in vitro by phospholipase A2-mediated oxidative and nonoxidative mechanisms. 767 73


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