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)

Lysophospholipase activity was measured in rabbit aorta using 1-[1-14C]palmitoyl-sn-glycero-3-phosphocholine as a substrate. The enzyme did not require Ca2+ for its activation and the maximal activation was attained in the presence of EGTA. Cholesterol dose-dependently inhibited the lysophospholipase activity in the soluble fraction and IC50 value was approximately 15 microM. Lineweaver-Burk plot revealed that cholesterol competitively inhibited lysophospholipase and Km values in the presence and absence of cholesterol (15.5 microM) were 12.3 and 2.8 microM, respectively. Vmax values were approximately 475 pmol/min.mg. The results suggest that cholesterol can interact with the enzyme per se, resulting in the inhibition of the lysophospholipase activity in rabbit aorta.
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PMID:Inhibition of lysophospholipase by cholesterol in rabbit aorta. 210 79

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

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

Legionella pneumophila, an intracellular pathogen causing a severe pneumonia, possesses distinct lipolytic activities which have not been completely assigned to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a protein with high homology to PlaA, the major secreted lysophospholipase A of L. pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we show that L. pneumophila plaC mutants possessed reduced phospholipase A and lysophospholipase A activities and lacked glycerophospholipid:cholesterol acyltransferase activity in their culture supernatants. The mutants' reduced phospholipase A and acyltransferase activities were complemented by reintroduction of an intact copy of plaC. Additionally, plaC conferred increased lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities to recombinant Escherichia coli. Furthermore, PlaC was shown to be another candidate exported by the L. pneumophila type II secretion system and was activated by a factor present in the bacterial culture supernatant dependent on the zinc metalloprotease. Finally, the role of plaC in intracellular infection of Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed, and plaC was found to be dispensable. Thus, L. pneumophila possesses another secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and lysophospholipase A activities. This enzyme is distinguished from the previously characterized phospholipases A and lysophospholipases A by its capacity not only to cleave fatty acids from lipids but to transfer them to cholesterol. Cholesterol is an important compound of eukaryotic membranes, and an acyltransferase might be a tool for host cell modification to fit the needs of the bacterium.
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PMID:Characterization of the major secreted zinc metalloprotease- dependent glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila. 1584 96

The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression. Following recent findings that the brain fatty acid composition of FSL is characterised by increased arachidonic acid (AA), we used electrospray tandem mass spectrometry and (1)H-NMR to examine lipid species in different brain areas. Cholesterol and sphingolipids were increased in the hypothalamus of the FSL rats. Furthermore, arachidonic acid-containing phosphatidylcholine (AA-PC) species were elevated with PC16:0/20:4, PC18:1/20:4 and PC18:0/20:4 (p<0.003) increased in the hypothalamus and striatum. In contrast, there was a decrease in some docosahexaenoic acid (DHA)-containing species, specifically PC18:1/22:6 (p<0.003) in the striatum and PE18:1/22:6 (p<0.004) in the prefrontal cortex. Since no significant differences were observed in the erythrocyte fatty acid concentrations, dietary or environmental causes for these observations are unlikely. The increase in AA-PC species which in this animal model may be associated with altered neuropathy target esterase activity, an enzyme involved in membrane PC homeostasis, may contribute to the depressive phenotype of the FSL rats.
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PMID:Arachidonic acid-containing phosphatidylcholine species are increased in selected brain regions of a depressive animal model: implications for pathophysiology. 1934 8

Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the "DNA--RNA-protein" synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes-cholesterol, phospholipids, and the ganglioside G(M1)--in context of the modern paradigm of acrosome exocytosis. We describe how these various- species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis.
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PMID:Lipid Regulation of Acrosome Exocytosis. 2719 52