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:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In ventilated rats, levels of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA) and phosphatidic acid, as well as their fatty acid contents, were measured in forebrain tissue after 1, 20 and 60 min of seizures induced by bicuculline. Cerebral energy state was also measured. PI decreased progressively throughout 60 min of seizures, whereas the levels of PIP and PIP2 did not change. DAG increased modestly and persistently. FFA increased markedly during the early seizure period, but decreased later. Following an initial drop, TAG rose above control. Phosphatidic acid did not change. The levels of ATP and energy charge potential decreased slightly and lactate accumulated. Stearic acid (18:0) and arachidonic acid (20:4) primarily accounted for the changes in the levels of the lipids. At the onset of seizures, the decrease of 18.0 and 20:4 in PI occurred in parallel with an enrichment of these fatty acids in FFA and DAG. Despite the fact that the losses of 18:0 and 20:4 from PI were quantitatively similar to each other at all times examined, the increase in free 18:0 was much larger than the increase in free 20:4 at 20 min of seizures. Concurrently there was a rise of 20:4 in TAG. As the FFA levels declined thereafter, 20:4 and docosahexaenoate (22:6) in TAG continued to increase. The results are consistent with the view that seizure activity stimulates the hydrolytic breakdown of brain phosphoinositides--the pathway catalyzed by phosphodiesterase of the phospholipase C type followed by lipases, and probably the pathway catabolized by phospholipases A as well. Preferential incorporation of polyunsaturated fatty acids into TAG-acyl residues may represent a mechanism to reduce the level of their free forms when the latter are produced in large amounts.
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PMID:Cerebral phosphoinositide, triacylglycerol and energy metabolism during sustained seizures induced by bicuculline. 303 62

The biosynthesis and post-translational modification of placental alkaline phosphatase were studied in human choriocarcinoma cells, JEG-3. Pulse-chase experiments with [35S]methionine demonstrated that placental alkaline phosphatase was synthesized as a major precursor form with Mr 63,000, which was then converted to a mature form with Mr 66,000, by processing of its N-linked oligosaccharides from the high-mannose type to the complex type. In addition, the two forms of the protein were found to be modified by a glycophospholipid, components of which were characterized by metabolic incorporation into placental alkaline phosphatase of 3H-labeled compounds such as myo-inositol, palmitic acid, stearic acid, mannose, glucosamine, and ethanolamine. When placental alkaline phosphatase labeled with these compounds was treated with phosphatidylinositol-specific phospholipase C or papain, the phospholipase C removed only the 3H-labeled fatty acids, whereas papain, that is known to cleave the C-terminal region, released all the radioactive glycolipid components including [3H]ethanolamine. More detailed analysis with shorter pulse-chase experiments demonstrated that placental alkaline phosphatase was primarily synthesized as a form with Mr 64,500 which was not yet labeled with [3H]palmitic acid. This form was converted by papain digestion to the above-mentioned major precursor with Mr 63,000. Taken together, these results suggest that placental alkaline phosphatase is initially synthesized as the precursor with Mr 64,500, which is immediately converted to the intermediate form with Mr 63,000 by simultaneously occurring proteolysis of the C terminus and replacement by the glycophospholipid, and finally to the mature form with Mr 66,000 by terminal glycosylation of its N-linked oligosaccharides. The glycophospholipid thus attached is considered to function as the membrane-anchoring domain of placental alkaline phosphatase.
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PMID:Biosynthesis of placental alkaline phosphatase and its post-translational modification by glycophospholipid for membrane-anchoring. 334 38

This study identifies and partially characterizes an insulin-sensitive glycophospholipid in H35 hepatoma cells. The incorporation of [3H]glucosamine into cell lipids was investigated. A major labeled lipid was purified by sequential thin layer chromatography using first an acid followed by a basic solvent system. After hydrochloric acid hydrolysis and sugar analysis by thin layer chromatography, 80% of the radioactivity in the purified lipid was found to comigrate with glucosamine. H35 cells were prelabeled with [3H]glucosamine for either 4 or 24 h and treated with insulin causing a dose-dependent stimulation of turnover of the glycophospholipid which was detected within 1 min. The purified glycolipid was cleaved by nitrous acid deamination indicating that the glucosamine C-1 was linked to the lipid moiety through a glycosidic bond. [14C]Ethanolamine, [3H]inositol, and [3H]sorbitol were not incorporated into the purified glycolipid. The incorporation of various fatty acids into this glycolipid was also studied. [3H]Palmitate was found to be preferentially incorporated while myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid were either not incorporated or incorporated less than 10% of palmitate. The purified glycolipid labeled with [3H]palmitate was cleaved by treatment with phospholipase A2 but was resistant to mild alkali hydrolysis suggesting the presence of a 1-hexadecyl,2-palmitoyl-glyceryl moiety in the purified lipid. Treatment of labeled glycophospholipid with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus generated a compound migrating as 1-alkyl,2-acyl-glycerol and a polar head group with a size in the range from 800 to 3500. These findings coupled with the nitrous acid deamination demonstrate that glucosamine was covalently linked through a phosphodiester bond to the glyceryl moiety of the purified glycolipid. These findings suggest that insulin acts on this glycophospholipid by stimulating an insulin-sensitive phospholipase C. This unique glycophospholipid may play an important role in insulin action by serving as precursor of insulin-generated mediators.
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PMID:Identification of a novel insulin-sensitive glycophospholipid from H35 hepatoma cells. 354 86

Primary cultures of mouse embryo palate mesenchyme cells were incubated with [3H]arachidonic acid and [14C]stearic acid in order to radiolabel their lipids. The cells were then washed, collected by centrifugation, and homogenized. Incubation of the homogenates under various conditions revealed that deoxycholate inhibited phospholipase A activity and stimulated a phospholipase C activity in these cells which preferentially degraded phosphatidylinositol (PI) compared to phosphatidylcholine (PC), -ethanolamine (PE), and -serine (PS). Expression of this phospholipase C (E.C. 3.1.4.10) activity was dependent on Ca2+ and had a pH optimum of no more than 7.0-7.5. Centrifugation of the homogenates at 105,000g for 30 min produced a membranous fraction that contained phospholipase C activity with characteristics similar to those of the enzyme found in the supernatant. Such a dual distribution of this enzyme may reflect that mouse embryo palate mesenchyme cells are neural crest in origin.
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PMID:Phospholipase C activity in palate mesenchyme cells: calcium and pH requirements, substrate specificity, and subcellular localization. 379 62

Once brain ischemia was induced in the gerbil cerebral fronto-parietal cortex, serial changes occurred in energy metabolites and various lipids. The amounts of inositol-containing phospholipids began to decrease immediately after energy failure, followed by an increase in the amount of 1,2-diacylglycerol with a subsequent liberation of arachidonic acid and other free fatty acids. The fatty acid compositions of inositol-containing phospholipids, of 1,2-diacylglycerols produced by ischemia, and of free fatty acids liberated during ischemia were quite similar. The amount of stearic acid liberated was much larger than that of arachidonic acid between 30 s and 1 min of ischemia. On the other hand, there was no significant decrease in the amount of the other phospholipids except for phosphatidic acid. Furthermore, there was also no change in the fatty acid composition of phosphatidylcholine or phosphatidylethanolamine throughout 15 min of ischemia. The amount of cytidine-monophosphate reached a peak (36.7 nmol/g wet wt) at 2 min of ischemia. These results indicated that arachidonic acid was predominantly liberated from inositol-containing phospholipids by phospholipase C, and by the diglyceride lipase and monoglyceride lipase system rather than from phosphatidylcholine or phosphatidylethanolamine by phospholipase A2 or plasmalogenase or choline phosphotransferase during the early period of ischemia.
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PMID:Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex. 379 19

Thrombin, histamine and ionophore A23187 stimulated human endothelial cells to release arachidonic acid and synthesize prostaglandins. To compare the activation of arachidonic acid release by these three stimuli in endothelial cells, we examined the intracellular lipid metabolism by prelabeling the cells with [14C]stearic acid and [3H]arachidonic acid. Thrombin stimulated the loss of 3H and 14C label from intracellular phospholipids. At the same time [3H]arachidonic acid and prostaglandins were released into the incubation medium. Thin layer chromatography analysis indicated that prostacyclin is the major metabolite formed followed by PGF2 alpha, PGE2, HHT and PGD2. In addition, several intracellular lipid metabolites were accumulated. These include: phosphatidic acid and 1,2-diacylglycerol detected by increase of both 14C and 3H radioactivity; lysophosphatidylinositol, lysophosphatidylethanolamine, and to a smaller extent lysophosphatidylcholine and lysophosphatidylserine detected by increase of 14C radioactivity. Like thrombin, both histamine and ionophore A23187 also stimulated release of arachidonic acid and synthesis of prostaglandins. Despite the different nature of the agonists, the type and the relative amount of prostaglandins synthesized in response to histamine and A23187 were similar to that stimulated by thrombin. The relative extents of hydrolysis of phospholipids and the accumulation of phosphatidic acid, 1,2-diacylglycerol and lysophospholipids are similar to that of 3H radioactivity and prostacyclin released into the medium and follow the order: ionophore A23187 greater than thrombin greater than histamine. These results suggest that in human endothelial cells, histamine, thrombin and ionophore A23187 directly or indirectly activated both phospholipase C and phospholipase A2 and these activations most likely involve mobilization of Ca2+.
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PMID:Prostacyclin synthesis and deacylation of phospholipids in human endothelial cells: comparison of thrombin, histamine and ionophore A23187. 392 46

The possibility that phospholipid deacylation may be a critical event in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-associated effects on mouse skin prompted us to examine in vitro the effects of TPA on arachidonic acid metabolism in neonatal mouse keratinocytes. Three-day old neonatal keratinocytes were prelabeled with [14C]arachidonic acid ([14C]AA) and [14C] stearic acid ([14C]ST) and used to characterize the lipases that were activated when these cells were treated with TPA in culture. Data from these studies demonstrate that phosphatidylcholine (PC) and phosphatidylinositol (PI) are the major phospholipids that undergo early hydrolysis to release arachidonic acid when challenged by TPA. Of particular interest was the novel observation of the hydrolysis of 14C-labeled PI in these keratinocytes, the accumulation of [14C]1,2-diacylglyceride and the lack of the [14C]diacylglyceride phosphorylation to form [14C]phosphatidic acid. This lack of [14C] phosphatidic accumulation implied that although TPA enhanced the hydrolysis of [14C]PI resulting in increased [14C]diacylglyceride it did not enhance the resynthesis of the [14C]PI via the phosphorylation of the [14C]diacylglyceride. Therefore, TPA probably is not involved in the turnover of PI in these cells but is involved in the activation of PC hydrolyzing phospholipase A2 and PI hydrolyzing phospholipase C in these keratinocytes releasing arachidonic acid which then undergoes oxygenation reactions to provide biologically active eicosanoids.
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PMID:Modulation of phospholipid metabolism in murine keratinocytes by tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. 393 Jun 15

Unsaturated fatty acids (oleic acid and arachidonic acid) activate purified protein kinase C independently of phospholipid and Ca2+. Oleic acid activation of protein kinase C is as effective as phosphatidylserine and Ca2+. Ka values for oleic acid and arachidonic acid are 50 and 53 microM, respectively. In contrast to the cis fatty acids, a trans form (elaidic acid) or a saturated fatty acid (stearic acid) has little or no effect on protein kinase C activation. If cis fatty acid liberation is physiologically important, this suggests that another mechanism may exist for protein kinase C activation, in addition to phospholipase C/phosphatidylinositol turnover signaling, possibly via the liberation of cis fatty acids by the Ca2+-dependent phospholipase A2 system.
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PMID:Direct activation of purified protein kinase C by unsaturated fatty acids (oleate and arachidonate) in the absence of phospholipids and Ca2+. 393 1

The triacylglycerols of very low density lipoproteins (VLDL) and of chylomicrons were analyzed in the fasting and postabsorptive states from normolipemic subjects and patients with Frederickson's Type II hyperlipoproteinemia, who subsisted on free choice diets, standard diets excluding lard, or were given a breakfast enriched in lard. The VLDL and chylomicrons were obtained by conventional ultracentrifugation, and the triacylglycerols were isolated by thin-layer chromatography (TLC). Representative sn-1,2-, sn-2-3- and sn-1,3-diacylglycerols were generated by partial Grignard degradation of the triacylglycerols and a stereospecific hydrolysis by phospholipase C of the mixed sn-1,2(2,3)-diacyl phosphatidylcholines prepared as intermediates. Representative sn-2-acylglycerols were obtained by hydrolysis with pancreatic lipase. Positional distribution of the fatty acids was established by subtracting in turn the fatty acid composition of the sn-2-position from the fatty acid composition of the sn-1,2- and sn-2,3-diacylglycerols. The molecular association of the fatty acids in the diacylglycerol moieties was determined by gas-liquid chromatography with mass spectrometry (GC/MS) of the tertiary-butyldimethylsilyl (t-BDMS) ethers. The molecular association of the fatty acids in the triacylglycerols was determined by 1-random 2-random 3-random calculation following experimental validation of the distribution. The results confirm a marked asymmetry in the positional distribution of the fatty acids in all triacylglycerol samples, with the palmitic acid predominantly in the sn-1-position, the unsaturated acids about equally divided between the sn-2- and sn-3-positions, and the stearic acid divided about equally between the sn-1- and sn-3-positions. The overall structure of the VLDL and chylomicron triacylglycerols from patients and control subjects was characterized by a non-correlative distribution of fatty acids under all dietary conditions.
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PMID:Comparative studies of triacylglycerol structure of very low density lipoproteins and chylomicrons of normolipemic subjects and patients with type II hyperlipoproteinemia. 398 38


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