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)

Lysophosphatidylcholine accumulates in the coronary sinus during pacing-induced myocardial ischemia in humans. This amphiphile accelerates Ca++ flux leading to cell injury in cultured cardiac myocytes, but it is not known whether lysophosphatidylcholine accumulation is injurious to human myocardium. In this study, we measured lysophosphatidylcholine in normal human myocardium obtained during cardiac surgery and exposed to ischemic conditions in vitro. Total lysophosphatidylcholine concentration (sum of lysophosphatidylcholine remaining in tissue and lysophosphatidylcholine released into the buffer) increased from 0.73 +/- 0.08 nmol/mg protein at baseline to 1.83 +/- 0.45 nmol/mg protein after 5 minutes of ischemia (p < 0.001), and was associated with evidence of cell injury (26% depletion of tissue lactate dehydrogenase). Significant lysophosphatidylcholine release into the incubation buffer (0.41 +/- 0.11 nmol/mg protein) also occurred after 5 minutes of ischemia. In contrast, there was no lysophosphatidylcholine accumulation or release and no lactate dehydrogenase depletion in oxygenated and perfused controls. Attenuation of lysophosphatidylcholine accumulation by incubation with lysophospholipase did not prevent cell injury. Lysoplasmalogen was not detected in ischemic tissue. We conclude that lysophosphatidylcholine accumulation is a marker of myocardial ischemia in humans.
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PMID:Lysophosphatidylcholine accumulation in ischemic human myocardium. 842 72

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

As part of our ongoing research on cardiac hypoxia tolerance we have conducted 31P nuclear magnetic resonance (NMR) studies of isolated, perfused, working hearts from freshwater turtles, animals that are well known for their ability to tolerate prolonged periods of anoxia. A striking feature of turtle heart spectra is an extremely high concentration of NMR visible phosphodiesters (PDEs). Cardiac spectra from mammals, on the other hand, typically exhibit only a small resonance in the PDE region. Our aim in this study was to compare myocardial PDE profiles between the highly hypoxia tolerant western painted turtle (Chrysemys picta bellii) and the relatively hypoxia sensitive softshelled turtle (Trionyx spinifer) in order to begin to rest the hypothesis that high constitutive levels of cytosolic PDEs may play a role in conferring hypoxia and ischemia tolerance on the myocardium. We also collected 31P-NMR spectra of PCA extracts of tissue from these species and from Kemp's ridley sea turtles (Lepidochelys kempi), as well as spectra from isolated hearts and PCA extracts of red-eared sliders (Trachemys [formerly Pseudemys] scripta]). Total NMR visible phosphodiesters make up 24 +/- 8.6% of the total NMR visible phosphorus in Chrysemys hearts, 20.7 +/- 5.9% in Trachemys hearts, but only 12.2 +/- 5.1% in Trionyx hearts (P < 0.05). We have identified three distinct PDEs in turtle hearts: glycerophosphorylcholine (GPC); glycerophosphorylethanolamine (GPE); and serine ethanolamine phosphodiester (SEP). SEP is the dominant compound in Chrysemys and Trachemys (79.3 +/- 10.2% and 84.7 +/- 3.7% of total PDE, respectively), while GPC is most abundant in Trionyx (74.0 +/- 4.3% of total PDE) and Lepidochelys (not quantitated). The function of this class of compounds is unclear but it has been suggested that cytosolic PDEs may function as lysophospholipase inhibitors, a role that would decrease the rate of membrane phospholipid turnover. Our comparative data suggest that cytosolic PDEs could play a role in phospholipid sparing during anoxic or ischemic stress in turtles but a direct test of this hypothesis awaits future experimentation.
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PMID:31P-NMR determinations of cytosolic phosphodiesters in turtle hearts. 950 28

Neuronal nuclei isolated from rabbit cerebral cortex were found to be enriched in an NEM-insensitive lysophosphatidic acid (lysoPA) phosphohydrolase activity. LysoPA is an inhibitor of the nuclear lysophosphatidylcholine (lysoPC) lysophospholipase, and by preserving lysoPC levels, lysoPA boosted the nuclear production of the acyl analogue of platelet-activating factor by promoting the acetylation of lysoPC (Baker and Chang, Mol. Cell Biochem., 1999, in press). The nuclear phosphohydrolase converts lysoPA to 1-monoacylglycerol, and thus eliminates this lysoPA inhibition of lysoPC lysophospholipase. The nuclear lysoPA phosphohydrolase specific activity was more than three times that observed for the nuclear lysoPA lysophospholipase (Baker and Chang, Biochim. Biophys. Acta 1438 (1999) 253-263) and represents a more active route for nuclear lysoPA removal. The neuronal nuclear lysoPA phosphohydrolase was inhibited at acidic pH, and also inhibited by calcium ions. The 1-monoacylglycerol product of the phosphohydrolase is rapidly degraded by neuronal monoacylglycerol lipase, an enzyme some sevenfold more active than the phosphohydrolase and sensitive to inhibition by arachidonoyl trifluoromethyl ketone (AACOCF(3)). Both acidic pH and free fatty acid inhibited the lipase. In the absence of AACOCF(3), production of fatty acid from lysoPA substrate could be largely attributed to the sequential actions of the nuclear phosphohydrolase and lipase. This facilitates fatty acid recycling back into phospholipid by lysophospholipid acylation when ATP levels are restored following periods of brain ischemia. At relatively low concentrations, sphingosine-1-phosphate, and alkylglycerophosphate were the most effective phosphohydrolase inhibitors while phosphatidic acid, alkylacetylglycerophosphate and ceramide were without effect. LysoPA is an interesting regulatory molecule that can potentially preserve lysophosphatidylcholine within the nuclear membrane for use in acetylation reactions. Thus conditions relevant to brain ischemia such as falling pH, falling ATP concentrations, rising fatty acid and intracellular calcium levels may, by slowing this metabolic path for lysoPA loss, promote the production of acyl PAF and contribute to the increased levels of the acetylated lipids noted in ischemia.
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PMID:A metabolic path for the degradation of lysophosphatidic acid, an inhibitor of lysophosphatidylcholine lysophospholipase, in neuronal nuclei of cerebral cortex. 1060 95

CoA-independent transacylase activities generating alkylacylglycerophosphocholine (AAGPC) from alkylglycerophosphocholine (1-alkyl GPC) were considerably enriched in neuronal nuclei isolated from rabbit cerebral cortex. Specific nuclear transacylation activities were 13 times the corresponding microsomal values. Several lysophospholipids, notably 1-acyl glycerophosphocholine (1-acyl GPC), 1-alkenyl GPC and 1-alkenyl GPE (1-alkenyl glycerophosphoethanolamine) inhibited the transacylation of 1-alkyl GPC. The inhibitory effects of 1-acyl GPC were seen in the presence of MAFP (methyl arachidonoylfluorophosphonate) or free oleate, compounds that inhibit neuronal nuclear lysophospholipase. When neuronal nuclei were preincubated with 1-alkyl GPC, the radioactive AAGPC product served as donor in transacylation reactions, to generate 1-alkyl GPC. In these nuclear reactions, 1-palmitoyl GPE and 1-palmitoyl GPC appeared to be poor acceptor substrates, when compared with corresponding 1-alkyl and 1-alkenyl analogues. The presence of free oleate or MAFP in the reactions containing 1-acyl GPC boosted the release of 1-alkyl GPC from AAGPC. These observations are of particular relevance to brain ischemia in which lysophospholipid, free fatty acid, and platelet-activating factor (PAF) levels rise dramatically. PAF can be made by the nuclear acetylation of 1-alkyl GPC, which is formed by nuclear transacylation mechanisms. Yet transacylase also removes 1-alkyl GPC, and thus this enzyme activity can regulate 1-alkyl GPC availability. Our observations indicate that lysophospholipids promote the formation of 1-alkyl GPC from nuclear AAGPC via transacylation, while free fatty acid likely prolongs the lifetime of 1-acyl lysophospholipids substrates by lysophospholipase inhibition. Similarly, once 1-alkyl GPC is formed, other lysophospholipids effectively compete with this 1-alkyl analogue and reduce its conversion back to AAGPC by transacylation. Free oleate, in this case, sustains 1-acyl lysophospholipid inhibitors of 1-alkyl GPC transacylation. Thus the cycle of transacylation may favour 1-alkyl GPC formation during ischemia, increasing levels of 1-alkyl GPC for nuclear acetylation reactions and PAF formation. The nuclear generation of PAF is of considerable importance as PAF can play regulatory roles in transcription events associated with inflammation.
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PMID:The regulation of CoA-independent transacylation reactions in neuronal nuclei by lysophospholipid, free fatty acid, and lysophospholipase: the control of nuclear lyso platelet-activating factor metabolism. 1120 49

cPLA2gamma was identified as an ortholog of cPLA2alpha, which is a key enzyme in eicosanoid production. cPLA2gamma was reported to be located in endoplasmic reticulum (ER) and mitochondria and to have lysophospholipase activity beside phospholipase A2 (PLA2) activity. However, subcellular localization, mechanism of membrane binding, regulation and physiological function have not been fully established. In the present study, we examined the subcellular localization and enzymatic properties of cPLA2gamma with C-terminal FLAG-tag. We found that cPLA2gamma was located not only in ER but also mitochondria even in the absence of the prenylation. Purified recombinant cPLA2gamma catalyzed an acyltransferase reaction from one molecule of lysophosphatidylcholine (LPC) to another, forming phosphatidylcholine (PC). LPC or lysophosphatidylethanolamine acted as acyl donor and acceptor, but lysophosphatidylserine, lysophosphatidylinositol and lysophosphatidic acid (LPA) did not. PC and phosphatidylethanolamine (PE) also acted as weak acyl donors. Reaction conditions changed the balance of lysophospholipase and transacylation activities, with addition of LPA/PA, pH>8, and elevated temperature markedly increasing transacylation activity; this suggests that lysophospholipase/transacylation activities of cPLA2gamma may be regulated by various factors. As lysophospholipids are known to accumulate in ischemia heart and to induce arryhthmia, the cPLA2gamma that is abundant in heart may have a protective role through clearance of lysophospholipids by its transacylation activity.
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PMID:Subcellular localization and lysophospholipase/transacylation activities of human group IVC phospholipase A2 (cPLA2gamma). 1950 Nov 89


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