Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycoinositol phospholipid membrane anchor of human erythrocyte acetylcholinesterase (EC 3.1.1.7) is composed of a glycan linked through a glucosamine residue to an inositol phospholipid that is resistant to the action of phosphatidylinositol-specific phospholipase C. Deamination cleavage of the glucosamine with nitrous acid released the inositol phospholipid which was purified by high performance liquid chromatography. Analysis by fast atom bombardment mass spectrometry with negative ion monitoring and by the complementary technique of collision-induced dissociation revealed molecular and daughter ions that indicated a plasmanylinositol with a palmitoyl group on an inositol hydroxyl. The intact membrane anchor was released from reductively methylated human erythrocyte acetylcholinesterase by proteolysis with papain or Pronase, deacylated by base hydrolysis, and purified by high performance liquid chromatography. Positive and negative ion fast atom bombardment mass spectrometry of the major products isolated by high performance liquid chromatography indicated the following structure for the complete glycoinositol phospholipid anchor. (formula; see text) Methylation of free amino groups by reduction with deuterium instead of hydrogen permitted determination of the number of free amino groups in individual fragment ions as further confirmation of structural assignments. The structure of the glycan portion of the human erythrocyte acetylcholinesterase membrane anchor appears to be similar to that described for Trypanosome brucei variant surface glycoprotein MITat 1.4 (variant 117) (Ferguson, M.A.J., Homans, S.W., Dwek, R.A., and Rademacher, T.W. (1988) Science 239, 753-759) except for the absence of a galactose antenna and the presence of a phosphorylethanolamine on the hexose adjacent to glucosamine.
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PMID:Structural characterization of the glycoinositol phospholipid membrane anchor of human erythrocyte acetylcholinesterase by fast atom bombardment mass spectrometry. 284 7

Brain cell membranes are known to abound in polyphosphoinositides (PPI) which contain large amounts of arachidonic acid and stearic acid. When a state of cerebral ischemia comes about, there occurs severe energy depletion and decomposition of PPI into diglyceride (DG) and inositol triphosphate (IP3) through activation of phospholipase C. Previous studies clarified rapid postischemic degradation of PPI, a time during which the metabolically active fraction of PPI is lost, but there have been no reports on PPI metabolism after the establishment of recirculation following ischemia. The authors examined relationship between the duration of the ischemia and the reversibility of PPI metabolism in rats with cerebral ischemia lasting 5 or 30 min that was followed by recirculation, and, further studied acyl group composition of PPI and DG in rats with 30 min of ischemia. Global cerebral ischemia was produced in male Wistar rats (220-250 g) by occlusion of basilar and bilateral common carotid arteries. The brains were frozen in situ at 1, 5, or 30 min of ischemia, or at 30 or 60 min of recirculation following either 5 or 30 min of ischemia. Phosphatidylinositol (PI), phosphatidylinositol, 4-phosphate (PIP), phosphatidylinositol, 4, 5-bisphosphate (PIP2), and DG were measured by TLC, and GLC. And also their acyl group compositions were determined. PI showed no significant changes. In contrast, both PIP and PIP2 sharply decreased immediately after onset of cerebral ischemia. then continued to fall gradually from 5 min onwards. And PIP and PIP 2 increased after onset of recirculation in both 5 and 30 min ischemia groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Polyphosphoinositide metabolism in temporary cerebral ischemia--the reversibility after recirculation]. 285 44

The glycolipids of the protozoan Leishmania major strain LRC-L119 belong to a class of glycoinositol phospholipids (GIPL) that show partial structural homology to the phosphatidylinositol-containing glycolipid membrane anchors of several eukaryotic proteins and the lipid moiety of L. major lipophosphoglycan. The GIPLs were the only glycolipids detected and were purified by octyl-Sepharose and thin layer chromatographies. Analysis of the native and dephosphorylated glycolipids (GIPLs 1-6) by gas chromatography-mass spectrometry revealed that the glycan moieties have between 4 and 10 saccharide residues and all contain mannose, galactose, and non-N-acetylated glucosamine. Some of the GIPLs also contain glucose (GIPL-6) and hexose monophosphate residues (GIPL 4-6). The presence of an inositol phospholipid moiety in all the GIPLs is indicated by the identification of 1 myo-inositol monophosphate residue/molecule and their susceptibility to phosphatidylinositol-specific phospholipase C. However, heterogeneity in the lipid moieties is indicated by differences in the compositional analysis and the behavior of the GIPLs on the thin layer chromatography after mild alkali hydrolysis or phospholipase A2 treatment. These results demonstrate that GIPLs 1-4 contain 1-alkyl-2-acylglycerol composed of saturated unbranched alkyl chains with carbon chain lengths of 18-26 and acyl chains of myristate, palmitate and stearate, whereas GIPL-5 and -6 contain lyso-alkylglycerol composed of mainly C24:0 and C26:0 alkyl chains. Analysis of the products of nitrous acid deamination demonstrates that these glycerolipids are present as alkylacylphosphatidylinositol (GIPLs 1-4) and 1-O-alkylglycerophosphoinositol (GIPL-5 and -6), respectively. GIPL-2 and -3 are labeled on the surface of living promastigotes with galactose oxidase/NaB[3H]4. These GIPLs also react with three monoclonal antibodies that recognize the surface of promastigotes and amastigotes of L. major and other Leishmania spp.
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PMID:A family of glycoinositol phospholipids from Leishmania major. Isolation, characterization, and antigenicity. 291 Aug 65

In primary cultures of sheep anterior pituitary cells extracellular ATP (ED50 0.4-0.8 microM) stimulated efflux of 45Ca2+ from a slow-turnover intracellular pool. ADP was also effective whereas AMP and adenosine were not. The ATP effect was not due to cell permeabilization as 100 microM ATP did not elicit efflux of 2-deoxy[3H]glucose metabolites. This 45Ca2+ mobilization may be mediated by inositol trisphosphate, since ATP (ED50 1 microM) stimulated inositol phosphate generation. These results demonstrate P2-purinoceptors in sheep anterior pituitary cells which are coupled to phospholipase C activation and intracellular Ca2+ mobilization, and raise the possibility of a regulatory role for extracellular ATP in the anterior pituitary.
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PMID:Extracellular adenosine triphosphate activates phospholipase C and mobilizes intracellular calcium in primary cultures of sheep anterior pituitary cells. 291 54

The metabolism of inositol-containing phospholipids during insulin secretion was studied in rat islets of Langerhans preincubated with [3H]inositol to label their phospholipids. Glucose (20 mM) caused a rapid breakdown of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate and an accumulation of inositol trisphosphate and inositol bisphosphate. This effect was maximal at 60s, did not require the presence of extracellular Ca2+, and was abolished by mannoheptulose (15 mM), but not by noradrenaline (1 microM). Mannose (20 mM) and DL-glyceraldehyde (10 mM) produced similar effects to those of glucose, but galactose (20 mM) and KCl (30 mM) were without effect. These results are compatible with the hypothesis that an early event in the stimulus-secretion coupling mechanism in the pancreatic B-cell is the rapid breakdown of polyphosphoinositides catalysed by phospholipase C. Moreover, they suggest that the breakdown of polyphosphoinositides is linked to sugar metabolism in the B-cell. This observation is important, since it demonstrates that events in a cell other than plasma-membrane receptor occupancy can promote polyphosphoinositide hydrolysis.
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PMID:Effect of glucose on polyphosphoinositide metabolism in isolated rat islets of Langerhans. 298 1

The unique features of renal phosphoinositide metabolism include an increase in tissue phosphoinositide levels induced by PTH. The significance of this finding remains unclear. Another unusual finding is the localization of phospholipase C activity in a BBMV preparation. As suggested in the review, the transducing mechanism involving cleavage of phosphoinositides by a phospholipase C would be expected to include a close association between phospholipase C and the plasma membrane. However, few attempts to localize phospholipase C activity in the plasma membrane have succeeded. The kidney also plays an unusual role in inositol metabolism in that it is the only organ that significantly catabolizes inositol. The kidneys also synthesize inositol. There is an enormous concentration of inositol in the outer medulla. This coexistence of significant inositol synthesis, breakdown, and the presence of extremely high amounts of free inositol is an intriguing but unexplained phenomenon. The substantial rate of endogenous renal inositol synthesis does not, however, preclude inositol deficiency states. There is a deficiency of inositol in diabetic peripheral nerve and in glomeruli isolated from diabetic rats. Such deficiencies may arise from a disturbance in the balance of synthesis, breakdown, and excretion of inositol, and particularly from the competition of glucose with the inositol transporter in the proximal tubule. Future studies of renal phosphoinositide metabolism need to address both basic cell biological questions and broader physiological or functional questions. The more basic issues include the question of which phosphoinositide is being attacked by agonist-stimulated phospholipase C. That is, are all the events explained by hydrolysis of PtdIns(4,5)P2, or are the other phosphoinositides hydrolyzed as well? Also, it would appear that stimulated phosphoinositide metabolism occurs quite early following receptor occupation, but there is still no way of selectively blocking stimulated phosphoinositide metabolism to see if it is a necessary first step in a cascade of events leading to cell response. Thus, the relationship of stimulated phosphoinositide metabolism to cell functions remains incompletely understood. At least two cellular functional or biochemical changes associated with stimulated phosphoinositide metabolism in the kidney have been identified, prostaglandin production and mesangial cell contraction. The regulation of prostaglandin production and its relationship to stimulated phosphoinositide metabolism are subjects of continuing study. The topic was recently reviewed by Hassid.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inositol phospholipid metabolism in the kidney. 301 Aug 24

Phosphoinositide hydrolysis in intact pancreatic islet cells was investigated in an indirect but dynamic manner by monitoring the efflux of radioactivity from islets prelabelled with [3H]inositol. A rise in glucose concentration provoked a rapid, modest but sustained increase in effluent radioactivity, this phenomenon being abolished in the absence of extracellular Ca2+ or presence of verapamil. The release of [3H]inositol was also stimulated at high extracellular K+ concentration, but not by gliclazide. Whether in the presence or absence of glucose, carbamylcholine provoked a marked increase in effluent radioactivity. The response to the cholinergic agent was decreased in the presence of verapamil or absence of extracellular Ca2+ and abolished in the presence of atropine or LiCl. These results suggest that an increase in cytosolic Ca activity, as caused by glucose or membrane depolarization, may cause activation of phospholipase C. In response to cholinergic agents, however, the enzymic activation, although modulated by Ca2+ availability, may result directly from the occupation of muscarinic receptors.
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PMID:Stimulation by glucose and carbamylcholine of phospholipase C in pancreatic islets. 301 46

Endogenous lipid droplets were prepared by subjecting fat cells to hypotonic shock and Triton X-100 treatment. The endogenous lipid droplets were found to show lipolysis in response to epinephrine, but not to show lipogenesis from glucose in response to insulin. These results indicated that the preparation of endogenous lipid droplets did not contain any intact fat cells capable of insulin-stimulated lipogenesis. Results with these endogenous lipid droplets showed that protein kinase inhibitor inhibited protein kinase-mediated hormone-sensitive lipase activity but did not reduce epinephrine-induced lipolysis. Cyclic AMP and dibutyryl cyclic AMP induced lipolytic activity in the presence of 80 mM KCl and their activities were not inhibited by protein kinase inhibitor. Phospholipase C inhibited epinephrine, cyclic AMP and dibutyryl cyclic AMP-induced lipolysis, but did not affect the lipolytic activity of either the activated or non-activated form of hormone-sensitive lipase. These results indicate the existence of a protein kinase inhibitor-insensitive and phospholipase C-sensitive lipolytic pathway in rat adipocytes.
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PMID:Studies on a protein kinase inhibitor-insensitive, phospholipase C-sensitive pathway of lipolysis in rat adipocytes. 302 21

The biochemical events initiated by mitogen in T lymphocytes are the subject of this paper. Following interaction of the mitogen with its receptors, a transmembrane 'trigger-type' signal is propagated which has both positive and negative correlates. The negative signal occurs with high mitogen concentrations and is associated with membrane freezing, microtubular aggregation, receptor capping, adenylate cyclase activation, and cellular cyclic AMP increases. The positive signal occurs with optimal mitogen concentrations and is associated with changes in membrane permeability and transport with influx of calcium and potassium ion and efflux of sodium, in transport processes for glucose, amino acids, and nucleosides, and in a collected series of early membrane lipid changes which can be considered essential for the positive signal. These lipid changes include the uptake of arachidonic acid and other fatty acids, choline, phosphate and other molecules, their incorporation into membrane phospholipids, particularly phosphatidylinositol (PI), and a turnover of PI with the production of inositol triphosphate, which can be related to calcium mobilization and diacylglycerol which activates a cytoplasmic protein kinase C. A key event associated with mitogen action is arachidonic acid release. Arachidonic acid may give rise to prostaglandins and thromboxanes as part of negative components of the signal through effects on the adenylate cyclase/cyclic AMP system. Arachidonic acid gives rise to eicosanoids like 5-, 11-, possibly 12- and 15-hydroxyperoxy and hydroxy eicosatetraenoic acids and leukotrienes B4 and C4. The activation of the 5-lipoxygenase, a critical calcium-dependent step, leads via the production of 5-HPETE and 5-HETE to the activation of membrane and soluble guanylate cyclase and the production of cyclic GMP. Cyclic GMP appears to be essential for mitogen activation and is associated with cyclic GMP-dependent protein kinase activation and the phosphorylation of a number of substrates. Calcium ion influx is clearly central to mitogen action. Calcium through its influx and mobilization from cellular stores is thought to contribute directly and indirectly through the action of calmodulin and protein kinase C to the activation of a number of enzymatic processes involved in the positive signal including phospholipase C, diglyceride kinase and lipase, 5-lipoxygenase, and guanylate cyclase. Cyclic GMP and calcium ion both participate in nuclear processes leading to RNA and protein synthesis. Interleukin 2 is associated with midcycle increases in cyclic GMP and entry into DNA synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transduction of signals in the activation of T lymphocytes: relation to leukemia. 304 Mar 20

Insulin is known to control a number of anabolic metabolic processes in a variety of target tissues through activation of cell surface receptors. It is clear that insulin receptor activation provokes increases in tyrosine kinase activity and autophosphorylation of the insulin receptor, but subsequent events have not been elucidated. Recently, it has become clear that insulin provokes the following rapid changes in phospholipid metabolism, which result in the generation of several intercellular signaling substances (or mediators): (1) hydrolysis of a phosphatidylinositol-glycan; (2) stimulation of de novo synthesis of phosphatidic acid; and (3) hydrolysis of phosphatidylcholine by a phospholipase C and/or D. Hydrolysis of the phosphatidylinositol-glycan leads to the release of polar headgroups, which serve as mediators to activate phosphatases, and may thereby account for a number of insulin effects on carbohydrate metabolism, lipid metabolism, and regulation of cyclic nucleotide metabolism. All three phospholipid effects of insulin also generate diacylglycerol, which activates protein kinase C, and this may contribute to insulin effects on glucose transport, ion and amino acid transport, protein synthesis, and gene expression (messenger RNA synthesis). Combined, the headgroup mediators and diacylglycerol-protein kinase C signaling systems may account for many, or perhaps most, of insulin's actions. Moreover, the three phospholipid effects of insulin appear to be coordinated, and may function as an integrated cycle to ensure the continued synthesis of lipids, which are the sources of the signaling substances during insulin action.
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PMID:Phospholipid signaling systems in insulin action. 305 93


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