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)

The de novo cytidine-5'-diphosphocholine (CDP-choline) pathway enzymes: choline kinase (CK); phosphorylcholine cytidyltransferase (CyT), and phosphorylcholine glyceride transferase (PCGT), and the phosphatidylcholine-lysophosphatidylcholine (PC-lysolPC) cycle pathway enzymes: lysophospholipase (LPL), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acyl-CoA LAT) were studied in the rabbit lung subcellular fractions. The purity of the fractions was examined by the marker enzymes and electron microscopy. The lamellar bodies had the highest concentration of phospholipids (10.0 mumol/mg protein, 80% of which was phosphatidylcholine (PC), about 10-fold higher than that of mitochondria (0.8) and microsomes (1.0) (50% of which was PC in both fractions). The lamellar bodies contained no enzymic activities of either the CDP-choline pathway or the PC-lysoPC cycle pathway. The enzymic activities of CK, CyT, LPL, and LAT were found mainly in the soluble fraction (about 40% for CK and CyT, and 70% for LPL and LAT); PCGT and acyl-CoA LAT were microsomal enzymes. Some general properties of PC-lysoPC cycle enzymes were also studied. The activities of LPL, LAT, and acyl-CoA LAT were not stimulated by the divalent metal ion Ca+. Their activities were inhibited by 10(-3) M diisopropyl phosphorofluoridate (DFP). The role of the PC-lysoPC cycle pathway enzymes in remodeling the lung PC is discussed.
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PMID:Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. I. Subcellular localization and properties. 19 61

Lysophosphatidylcholine (lysoPC), a breakdown product of phosphatidylcholine (PC), might be important in pulmonary PC synthesis through fatty acid exchange reactions. This study defines the levels of three of the enzymes of the PC-lysoPC cycle pathway (lysophospholipase (LPL) (EC. 3.1.1.5), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acryl-CoA LAT) (EC. 2.3.1.23)) in developing fetal rabbit lung and compared them with the enzymes of the CPD-choline synthetic pathway (choline kinase (CK) (EC. 2.7.1.32), phosphorylcholine cytidyl transferase (CyT) (EC. 2.7.7.15), and phosphorylcholine glyceride transferase (PCGT) (EC. 2.7.8.2). Lung homogenates of fetal rabbits of known gestation, newborn, and adult rabbits were used for the enzyme, protein, and phospholipid analyses. Total lung phospholipid, PC, and protein increased with gestational age. Thirty days' gestation, newborn, and maternal lung activities of CK, CyT, and PCGT had decreased to only 50% of their activities at 22-26 days' gestation. In contrast, LPL and LAT activities increased 4-5-fold from 22-26 days to 30 days' gestation, and increased further in the newborn lung, finally to a level matching maternal lung (about 8-10-fold higher than the 22-26 days' gestation activities). The microsomal acyl-CoA LAT also showed a similar increasing activity with gestational age. In fetal lung, enzymic activities for the apparent major PC synthetic pathway decreased. In contrast, the marked increases in LPL, LAT, and acyl-CoA LAT activities with increasing gestational age and at birth suggests importance of the PC lysoPC cycle pathway in regulating synthesis and turnover with maturation.
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PMID:Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. II. Marked differences in the effect of gestational age on activity compared to the CDP-choline pathway. 19 62

2-Acyl-glycerophosphoethanolamine (2-acyl-GPE) acyltransferase and acyl-acyl carrier protein (acyl-ACP) synthetase are thought to be dual catalytic activities of a single inner membrane enzyme. A filter disc replica print method for the detection of acyl-ACP synthetase activity by colony fluorography was used to screen a mutagenized population of cells for acyl-ACP synthetase mutants (aas). All aas mutants lacked both acyl-ACP synthetase and 2-acyl-GPE acyltransferase activities in vitro. There was no detectable acyl-CoA-independent incorporation of exogenous fatty acids into phosphatidylethanolamine or the major outer membrane lipoprotein in aas mutants. Exogenous lysophospholipid uptake and acylation was also lacking in aas mutants. Lipoprotein acylation by phospholipids synthesized by the de novo biosynthetic pathway was not affected in aas mutants showing that this gene product was not directly involved in lipoprotein biogenesis. The aas mutants had an altered membrane phospholipid composition and accumulated both 2-acyl-GPE and acylphosphatidylglycerol. Acylphosphatidylglycerol accumulation was due to the transacylase activity of lysophospholipase L2 (the pldB gene product) since aas pldB double mutants accumulated 2-acyl-GPE, but not acylphosphatidylglycerol. The aas allele was mapped to 61 min of the Escherichia coli chromosome, and the deduced gene order in this region was thyA-aas-lysA. The biochemical, physiological, and genetic analyses of aas mutants support the conclusion that 2-acyl-GPE acyltransferase and acyl-ACP synthetase are two activities of the same protein and confirm that this enzyme system participates in membrane phospholipid turnover and governs the acyl-CoA independent incorporation of exogenous fatty acids and lysophospholipids into the membrane.
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PMID:Isolation and characterization of Escherichia coli K-12 mutants lacking both 2-acyl-glycerophosphoethanolamine acyltransferase and acyl-acyl carrier protein synthetase activity. 164 29

Lysophosphatidylcholine (lysoPC) is an arrhythmogenic phospholipid metabolite which accumulates in the ischemic myocardium. Reduced catabolism of lysoPC has been proposed to be one of the biochemical mechanisms responsible for the increase in lysoPC content. In this investigation we compared the microsomal catabolism of exogenous labeled lysoPC in isolated perfused rat and guinea pig hearts. Analysis of the amount of radioactivity in microsomal phosphatidylcholine (PC) and free fatty acid (FFA) was used as an index of the participation in lysoPC clearance by acylation catalyzed by acyl-CoA:lysoPC acyltransferase and deacylation catalyzed by lysophospholipase, respectively. There was no significant difference in the incorporation of radioactivity into rat and guinea pig heart microsomes; however, the patterns of radioactivity in lysoPC metabolites were notably different. Equal participation by deacylation and reacylation was observed in rat microsomes, whereas deacylation was clearly the preferred route for lysoPC clearance in guinea pig microsomes. Modulation of enzyme activity by treatment of the isolated heart with pHMB, a sulfhydryl agent, was used to probe the relationship among acylation, deacylation and the extent of lysoPC clearance. In guinea pig microsomes impairment of lysoPC acylation was not associated with any change in the amount of radioactivity in lysoPC because of a compensatory increase in deacylation. In contrast, impaired deacylation in rat microsomes led to significant elevations in the amount of radioactivity in lysoPC. We conclude, therefore, that in intact perfused rat and guinea pig hearts the relative participation of acylation and deacylation in lysoPC clearance differs. Moreover, we propose that the level of deacylation by lysophospholipase is an important factor in the extent of clearance of lysoPC.
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PMID:The catabolism of exogenous lysophosphatidylcholine in isolated perfused rat and guinea pig hearts: a comparative study. 185 1

Phospholipid peroxidation and the activities of phospholipase A, acyl Coenzyme A:lysophospholipid acyltransferase and lysophospholipase were measured in isolated bovine rod outer segments (ROS) that were incubated in the presence or absence of the added antioxidants, vitamin E and dithiothreitol (DTT), and additionally in light or dark. DTT and vitamin E significantly inhibit both lipid peroxidation and the enzyme activities. These results suggest that one function of the enzymes for molecular replacement of fatty acids in ROS, is removal of peroxidized fatty acids and thus protection of the membrane phospholipids and proteins from further oxidative damage.
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PMID:Effects of the antioxidants dithiothreitol and vitamin E on phospholipid metabolism in isolated rod outer segments. 206 29

It has been shown for the first time that lysosomal (tritosomal) membranes of rat liver contain enzymes that are responsible for the deacylation-reacylation of phospholipids; their activity optimum lies at pH 7.0. Deacylation of lysosomal membrane phospholipids is controlled by a cascade of enzymatic reactions involving Ca2(+)-dependent phospholipase A1 which exhibits the maximal activity at 2.5 mM Ca2+ and at neutral values of pH, as well as lysophospholipase. Reacylation of lyso-derivatives of phospholipids is catalyzed by Mg2(+)-activated oleoyl-CoA:lysophosphatidylcholine acyltransferase having an activity optimum at pH 7.2.
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PMID:[The enzymatic system of phospholipid deacylation-reacylation in rat liver lysosomal membranes]. 207 42

Human umbilical vein endothelial cells (HUVEC) in culture synthesize prostacyclin (PGI2) as the predominant metabolite of arachidonic acid which is derived from the deacylation of phospholipids. Under basal-unstimulated condition, PGI2 release from HUVEC is extremely low; however, when endothelial monolayers were preincubated with the natural vitamin E (R,R,R-alpha-tocopherol), we found a dose-dependent potentiation of basal PGI2 release. When HUVEC were stimulated with arachidonate or ionophore A23187, there was a dose-dependent increase of PGI2 release in response to tocopherol enrichment. When HUVEC were labelled with [Me-3H]choline followed by A23187 stimulation, a significantly higher lysophosphatidylcholine was found in the tocopherol-enriched cells, suggesting a change in enzymes involved in phosphatidylcholine metabolism. Analysis of these enzymes revealed that phospholipase A2 activity was enhanced by tocopherol enrichment, whereas lysophospholipase and acyl-CoA acyltransferase were unaffected. To determine the specificity of the tocopherol molecule, different analogues were tested for their PGI2 potentiating activity. Results showed that the free hydroxyl group on the chromanol ring as well as the phytyl side-chain are absolutely required to stimulate PGI2 release, whereas, different methyl locations and substituents on the chromanol ring had no effect. These studies demonstrated that tocopherol potentiates basal PGI2 release in HUVEC and in contrast to its reported inhibitory role in rat platelets, myocardium and neutrophils, tocopherol stimulates phospholipase activity in HUVEC.
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PMID:R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule. 210 79

An important feature in the remodelling of fatty acyl chains in cellular phospholipids is the acylation of lysophospholipids. Since lysophospholipids are cytolytic at high concentrations, the acylation reaction may provide an alternate pathway for the removal of cellular lysophospholipids. However, the physiological role of the acylation process in the maintenance of lysophospholipid levels in mammalian tissues has not been clearly defined. In this study, methyl lidocaine was found to inhibit both lysophosphatidylcholine:acyl-CoA and lysophosphatidylethanolamine:acyl-CoA acyltransferase activities in the hamster heart, but the drug had no effect on the other lysophospholipid metabolic enzymes. When the heart was perfused with 0.5 mg methyl lidocaine/mL, acyltransferase activities were attenuated, but there was no change in the activities of phospholipase A or lysophospholipase. The levels of the major lysophospholipids in the heart were not altered by methyl lidocaine perfusion. When the hearts were perfused with labelled lysophospholipid in the presence of methyl lidocaine, there was a reduction in the formation of the phospholipid and an increase in the release of the free fatty acid. However, the labelling of lysophospholipid in the heart was not altered by methyl lidocaine. We postulate that the acylation reaction has no direct contribution to the maintenance of the lysophospholipid levels in the heart.
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PMID:The effect of methyl lidocaine on lysophospholipid metabolism in hamster heart. 222 99

Alterations in the lipid composition of lung microsomal membranes occur in oleic acid-induced respiratory distress. The marked decrease in the phosphatidylcholine/lysophosphatidylcholine molar ratio could be related with an altered metabolism of lysophosphatidylcholine in these membranes. Results revealed that the activity of phospholipase A increased whereas that of acyl-CoA:lysophosphatidylcholine acyltransferase decreased. Microsomal lysophospholipase activity remained unchanged. On the other hand, the microsomal enzyme system involved in the de novo synthesis of diacylglycerol was impaired, and cholinephosphotransferase activity was lowered. These changes in the activity of some membrane-bound enzymes were not caused by changes in the membrane lipid fluidity since lipid structural order parameter (SDPH) did not change and neither did the major factors on which the fluidity depends. The possible significance of microsomal lipid alterations in the pathogenesis of respiratory distress induced by oleic acid is discussed.
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PMID:Association of changes in lysophosphatidylcholine metabolism and in microsomal membrane lipid composition to the pulmonary injury induced by oleic acid. 232 51

The metabolism of lysophosphatidylcholine (LPC) in non-ischemic and ischemic canine heart was investigated by in vitro enzyme analysis. Selected subcellular fractions were assayed for the LPC-producing enzyme phospholipase A and the LPC-eliminating enzymes LPC:acyl-CoA acyltransferase, LPC:LPC transacylase and lysophospholipase. The canine heart was found to contain all enzymes differing, however, in subcellular distribution and specific activity. Phospholipase A activity did not change significantly in any of the fractions prepared from the ischemic tissue of hearts rendered ischemic for 1, 3 or 5 hr when compared to non-ischemic tissue. Changes in the activity of the microsomal LPC:acyl-CoA acyltransferase over the course of 5 hr of ischemia were observed. Significant decreases in the activity of the cytosolic and microsomal lysophospholipases were detected especially after 3 and 5 hr of ischemia. Similarly, a decrease in the activity of the microsomal LPC:LPC transacylase was noted after 3 and 5 hr of ischemia. Our results suggest that impaired catabolism of LPC rather than an enhanced production of LPC is the principal mechanism for the increase in LPC levels in the ischemic canine heart.
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PMID:Mechanism of lysophosphatidylcholine accumulation in the ischemic canine heart. 239 14


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