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)

Two calcium-independent phospholipases isolated from guinea pig pancreas (lipase Ia, 37 kDa) and from guinea pig intestine (phospholipase B, 97 kDa) have been used to probe the mechanism of phospholipase inhibition by lipocortin. In the presence of calcium, both enzymes were inhibited by lipocortin I in a manner very similar to the inhibition of pig pancreas phospholipase A2. By using phospholipases that lack a requirement for calcium, we have for the first time been able to dissociate enzymatic activity from the role of calcium in the inhibitory process. It was found that lipocortin was without effect against phospholipase A1 and phospholipase B in the absence of calcium, under which conditions the inhibitory protein is unable to interact with anionic phospholipid surfaces. The same behavior toward phospholipase A1 was observed with two other related proteins, endonexin II or lipocortin V, and p68/67-kDa calelectrin or lipocortin VI. Together with the observation that lipocortins are active only in the presence of limited amounts of substrate, these data give further support to the "surface depletion model" of lipocortin inhibition, rather than to a mechanism involving a direct interaction between enzyme and inhibitor.
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PMID:Calcium-independent phospholipases from guinea pig digestive tract as probes to study the mechanism of lipocortin. 213 21

The effect of phorbol ester pretreatment of human vascular smooth muscle cells (hVSMC) was studied with respect to regulation of endothelin (ET)-receptor binding and cellular responses to ET. The capacity of hVSMC to bind ET was decreased (by approximately 50% at maximum) after phorbol exposure, and this reductive effect was both rapid (t 1/2 approximately 10 min.) and sustained (for up to 24 hrs. of chronic phorbol exposure). Phorbol pretreatment inhibited both inositol phosphate and diacylclycerol production responses of hVSMC to ET in a manner that was time-dependent and sustained. Phorbol pretreatment also produced a persistent reduction in the ability of ET to release isotopically-labelled arachidonic and/or its metabolites from hVSMC, but importantly ionomycin-stimulated release was similarly negatively affected. Furthermore, ET-induced accumulation of the phospholipase A2/phospholipase B-derived inositol phospholipid metabolite, glycerophosphoinositol, was not different between control and phorbol-treated hVMSC. The mechanism whereby phorbol exerts differential, but notably sustained inhibitory effects on ET-promoted signal transduction pathways are thus complex and illustrative of the selectivity of protein kinase C in regulating cellular responses.
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PMID:Phorbol ester promotes a sustained down-regulation of endothelin receptors and cellular responses to endothelin in human vascular smooth muscle cells. 215 74

Similarities in substrate specificity, localization and molecular weight between villus membrane phospholipase A2/lysophospholipase and carboxylester lipase of pancreatic origin suggested their possible identity. To test this, a preparation of the phospholipase A2/lysophospholipase released from brush border vesicles by papain was compared to authentic, pancreatic carboxylester lipase. Susceptibility of both activities to the inhibitor, diisopropylfluorophosphate, was consistent with their identity, but inconclusive. It also indicated that two populations of phospholipase A2 species may be present in the papain-released preparation. However, comparison of binding of the activities to Sepharose-coupled, anti-carboxylester-lipase IgG indicates that they are immunologically distinct.
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PMID:Is intestinal villus phospholipase A2/lysophospholipase bound pancreatic carboxylester lipase? 228 Jun 82

In the macrophages (M phi) obtained from mouse peritoneal exudates, five kinds of phospholipid-deacylating activities were detected using phosphatidylethanolamine (PE) and phosphatidylcholine (PC) labeled with [1-14C]oleic acid either in 1- or 2- position and 1- [1-14C]oleoyl-lysoPE, as substrates. Two types of phospholipipase A1 with pH optima of 4 to 6 and 8, respectively, and two types of phospholipase A2 activities with pH optima of 4 to 5 and 8, respectively, were identified. A detected lysophospholipase activity exhibited a broad pH optimum between 4 and 8. Both types of the phospholipase A1 and A2 of M phi hydrolyzed PE more than PC. Exogenously added Ca2+ did not increase the enzymatic activities. A comparison was made of three kinds of the M phi-phospholipid deacylating activities at pH8, after challenging the M phi with Mycobacterium lepraemurium, Escherichia coli, zymosan, or latex beads for 17 hours at 37 degrees C. The bacteria used to the phagocytosis were autoclaved. When the M phi were challenged with M. lepraemurium, the phospholipase A1, A2 and lysophospholipase activities were stimulated by about 160%, 150% and 140%, respectively. However, when challenged with E. coli, the phospholipase A1 activity remarkably decreased by about a third, although the phospholipase A2 activity was stimulated by about 150% that is similar to the challenge with M. lepraemurium. An inflammatory substance, zymosan seemed an effective inducer of the phospholipase A2, the enzymatic activity was remarkably stimulated by 260%, when challenged with 200 micrograms of zymosan. The increase in phospholipase A2 activity of the M phi pretreated with the bacteria or zymosan seems to result in an increase in the hydrolysis of arachidonic acid from the M phi-phospholipids to synthesize its inflammatory oxygenated metabolites. The lysophospholipase activity was not stimulated by the substances used to challenge the M phi, except for M. lepraemurium. No significant increase in three kinds of phospholipid-deacylating activities was observed after challenging the M phi with latex beads. It was considered from the above results that the M phi-phospholipid-deacylating activities at pH8 might be affected by sort of the ingested substances.
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PMID:[Phospholipid-deacylating activities of the mouse peritoneal macrophages during phagocytosis]. 248 84

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

The substrate specificity of Escherichia coli outer membrane phospholipase A was analyzed in mixed micelles of lipid with deoxycholate or Triton X-100. Diglycerides, monoglycerides, and Tweens 40 and 85 in Triton X-100 are hydrolyzed at rates comparable to those of phospholipids and lysophospholipids. p-Nitrophenyl esters of fatty acids with different chain lengths and triglycerides are not hydrolyzed. The minimal substrate characteristics consist of a long acyl chain esterified to a more or less hydrophilic headgroup as is the case for the substrate monopalmitoylglycol. Binding occurs via the hydrocarbon chain of the substrate; diacyl compounds are bound three to five times better than monoacyl compounds. When acting on lecithins, phospholipase A1 activity is six times higher than phospholipase A2 activity or 1-acyl lysophospholipase activity. Activity on the 2-acyl lyso compound is about two times less than that on the 1-acyl lysophospholipid. The enzyme therefore has a clear preference for the primary ester bond of phospholipids. In contrast to phospholipase A1 activity, phospholipase A2 activity is stereospecific. Only the L isomer of a lecithin analogue in which the primary acyl chain was replaced by an alkyl ether group is hydrolyzed. The D isomer of this analogue is a competitive inhibitor, bound with the same affinity as the L isomer. On these ether analogues the enzyme shows the same preference for the primary acyl chain as with the natural diester phospholipids. Despite its broad specificity, the enzyme will initially act as a phospholipase A1 in the E. coli envelope where it is embedded in phospholipids.
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PMID:Kinetic characterization of Escherichia coli outer membrane phospholipase A using mixed detergent-lipid micelles. 265 33

A phospholipase A2 activity directed against phosphatidylcholine was previously described in brush-border membrane from guinea pig intestine (Diagne, A., Mitjavila, S., Fauvel, J., Chap, H., and Douste-Blazy, L. (1987) Lipids 22, 33-40). In the present study, this enzyme was solubilized either with Triton X-100 or upon papain treatment, suggesting a structural similarity with other intestinal hydrolases such as leucine aminopeptidase, sucrase, or trehalase. The papain-solubilized form, which is thought to lack the short hydrophobic tail responsible for membrane anchoring, was purified 1800-fold to about 90% purity by ion exchange chromatography on DEAE-Sephacel, gel filtration on Ultrogel AcA44, and hydrophobic chromatography on phenyl-Sepharose. Upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, a main band with an apparent molecular mass of 97 kDa was detected under reducing and nonreducing conditions. In the latter case, phospholipase A2 activity could be recovered from the gel and was shown to coincide with the 97-kDa protein detected by silver staining. The enzyme activity was unaffected by EGTA and slightly inhibited by CaCl2. The purified enzyme displayed a similar activity against phosphatidylcholine and phosphatidylethanolamine, whereas 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine hydrolysis was reduced by 50% compared to diacylglycerophospholipids. Using phosphatidylcholine labeled with either [3H]palmitic acid or [14C]linoleic acid in the 1- or 2-positions, respectively, the purified enzyme catalyzed the removal of [3H]palmitic acid, although at a lower rate compared to [14C]linoleic acid. This resulted in the formation of sn-glycero-3-phosphocholine, but only 1-[3H]palmitoyl-sn-glycero-3-phosphocholine was detected as an intermediary product. In agreement with this, 1-acyl-2-lyso-sn-[14C]glycero-3-phosphocholine was deacylated at almost the same rate as the sn-2-position of phosphatidylcholine. Since upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the two hydrolytic activities were detected at the same position as 97-kDa protein, the enzyme is thus considered as a phospholipase A2 with lysophospholipase activity (phospholipase B), which might be involved in phospholipid digestion.
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PMID:Purification of a new, calcium-independent, high molecular weight phospholipase A2/lysophospholipase (phospholipase B) from guinea pig intestinal brush-border membrane. 272 44

Orientotoxin I, a neurotoxin of presynaptic effect having a lysophospholipase activity, and orientotoxin II, a highly toxic phospholipase A2, were isolated from the hornet Vespa orientalis venom, and their primary structures were determined. Despite their different functional activity, orientotoxin I and II proved to be structural homologues, differing significantly in the amino acid sequence from well-known toxic phospholipase from other sources.
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PMID:[Amino acid sequence of orientotoxins I and II from the venom of the hornet Vespa orientalis]. 274 6

We have attempted to determine the size and membrane orientation of a recently described rat jejunal brush-border protein possessing phospholipase A2 and lysophospholipase activities (phospholipase B) (Pind, S. and Kuksis, A. [1988] Biochim, Biophys. Acta 938, 211-221). The phospholipase A2 and lysophospholipase activities were renatured following nonreducing sodium dodecyl sulphate polyacrylamide gel electrophoresis of the total membrane proteins and were shown to migrate as a component of a protein band having a relative molecular mass of 170 kDa. This band accounted for approximately 1% of the total Coomassie Blue staining proteins. Phospholipase B was also shown to be solubilized from the membranes, in an active form, by a proteolytic digestion with papain. Papain solubilization resulted in a loss of the hydrophobic properties observed for the intact phospholipase. These results suggest that the active site of the phospholipase projects from the luminal surface of the membrane vesicles. In support of this, phospholipase activity towards exogenous, detergent-solubilized phosphatidylcholine was demonstrated under conditions in which the membranes remained intact. We conclude that the phospholipase B has the characteristics of a stalked, brush-border membrane protein and may be considered as another digestive enzyme anchored in this membrane.
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PMID:Association of the intestinal brush-border membrane phospholipase A2 and lysophospholipase activities (phospholipase B) with a stalked membrane protein. 275 13

The degradation of lipids by endogenous hydrolytic activity has been studied in rat cardiac tissue deliberately damaged by freezing and thawing prior to storage under anoxic conditions. Aliquots of the freeze-thawed material were kept at 37 degrees C under an atmosphere of N2 up to 120 minutes. Triacylglycerol was hydrolyzed at a rate of 0.14 mumol fatty acids per minute per gram dry weight of tissue. Hydrolysis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was associated with proportional production of lyso PC and lyso PE, respectively. This finding indicates that the activity of lysophospholipase is negligible in autolyzing cardiac tissue. The rate of hydrolysis of PC and PE was found to be 0.10 and 0.06 mumol per minute per gram dry weight of tissue. The observation that lyso PC and lyso PE mainly contained saturated and mono-unsaturated fatty acids indicates that phospholipase A2 rather than A1 is active in autolyzing cardiac tissue. The accumulation of fatty acids corresponded with the loss of triacylglycerol and phospholipids from the tissue during 120 minutes of autolysis.
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PMID:Degradation of phospholipids and triacylglycerol, and accumulation of fatty acids in anoxic myocardial tissue, disrupted by freeze-thawing. 278 32


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