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)

3,4-Dihydroxy[3-(3)H]butyl-1-phosphonate, and analogue of glycerol 3-phosphate, is incorporated into a very polar lipid material by cultures of Escherichia coli strain 8 and in vitro by CDP-diglyceride:sn-glycerol-3-phosphate phosphatidyltransferase. These labeled lipids have been fractionated by column chromatography on DEAE-cellulose, revealing that only one labeled compound is formed in vitro, while four are synthesized in vivo. The main component of the material formed by intact cells has been shown to be identical with that produced enzymatically. This species has been identified as the phosphonic acid analogue of phosphatidylglycerophosphate [(1,2-diacyl)-sn-glyceryl-D-4'-phosphoryloxy-3'-hydroxybutyl-1'-phosphonate]. Hydrolysis of this novel lipid with phospholipase C resulted in the production of diglyceride and a water-soluble derivative of 3,4-dihydroxybutyl-1-phosphonate and inorganic phosphate in a molar ratio of 1.03/1. Enzymatic analysis of the phosphonate liberated in this manner showed it to be the D enantiomer, thereby confirming the proposed structure of the lipid analogue. The analogue of phosphatidylglycerophosphate did not turn over and appeared to have no precursor-product relationship to the other labeled lipids derived from 3,4-dihydroxy[3-(3)H]butyl-1-phosphonate in vivo. Analysis of the other three labeled products revealed the tritium to be present on glycerol 3-phosphate and not intact phosphonate, indicating some metabolic degradation of the latter. Examination of cell components other than lipids revealed little incorporation of label, while a significant amount of tritium was found to be present in a distillable form, 3H2O. Experiments with mutants of E. coli lacking the known glycerol-3-phosphate dehydrogenases indicated that these enzymes are not responsible for the removal of tritium from from 3,4-dihydroxy[3-(3)H]butyl-1-phosphonate in vivo. Indirect evidence suggests that the inhibition of cell growth by this analogue is not due to its catabolic products.
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PMID:Metabolic fate of 3,4-dihydroxybutyl-1-phosphonate in Escherichia coli. 78 74

Rabbit lung microsomes were found to catalyze CMP-dependent incorporation of [14C]glycerol 3-phosphate into a total lipid extract. The radioactively labeled products in the lipid extract were identified as phosphatidylglycerol and phosphatidylglycerol phosphate. CMP-dependent incorporation of [14C]glycerol 3-phosphate by lung microsomes proceeded optimally at pH 7.4 and required Mn2+. The apparent Km value for CMP in this reaction was calculated to be 0.19 mM. No other cytidine nucleotide could substitute completely for CMP in supporting [14C]glycerol 3-phosphate incorporation into lipid. Cytosine-beta-D-arabinofuranoside-5'-monophosphate-dependent incorporation of [14C]glycerol 3-phosphate was observed at pH 8.5 but not at pH 6.8 CMP-dependent incorporation of [14C]glycerol 3-phosphate by microsomes was inhibited by inositol. The optimal in vitro rates of CMP-dependent and CDP diacylglycerol-dependent incorporation of [14C]glycerol 3-phosphate into lipid were similar (approximately 1 nmol . mg-1 protein . h-1) and were not additive. Both CMP -dependent and CDP diacylglycerol-dependent incorporation of [14C]glycerol 3-phosphate by lung microsomes appeared to involve CDPdiacylglycerol:glycerol-3-phosphate phosphatidyltransferase. However, the specific activity of this enzyme in a particular subcellular fraction did not relate directly in the extent of CMP-dependent [14C]glycerol 3-phosphate incorporation in that fraction. Preincubation of lung microsomes with 5 mM CMP plus 3 mM phosphatidylinositol increased CMP-dependent incorporation of [14C]glycerol 3-phosphate. When lung microsomes were depleted specifically of phosphatidylinositol by incubating with a phosphatidylinositol-specific phospholipase C, CMP-dependent incorporation was diminished. The Mn2+ requirement for CMP-dependent incorporation of [14C] glycerol 3-phosphate, its phosphatidylinositol requirement and its inhibition by Triton X-100 (0.2%) were not features shared by CDPdiacylglycerol-dependent incorporation of [14C]glycerol 3-phosphate but were characteristics of the reverse reaction catalyzed by CDPdiacylglycerol: inositol phosphatidyltransferase. Together with the previous finding of a developmental increase in the CMP content of fetal rabbit lung, these observations are consistent with a role for CMP in the regulation of the phosphatidylinositol and phosphatidylglycerol content of lung surfactant during lung maturation.
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PMID:CMP-dependent incorporation of [14C]Glycerol 3-phosphate into phosphatidylglycerol and phosphatidylglycerol phosphate by rabbit lung microsomes. 707 21

The effect of phospholipase C treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells with phosphatidylcholine-specific Clostridium welchii phospholipase C reduced the pool size of phosphatidylcholine compared with controls whereas the pool size of cardiolipin and phosphatidylglycerol were unaffected. Pulse labeling experiments with [1,3-3H]glycerol and pulse-chase labeling experiments with [1,3-3H]glycerol were performed in cells incubated or pre-incubated in the absence or presence of phospholipase C. In all experiments, radioactivity incorporated into cardiolipin and phosphatidylglycerol were reduced in phospholipase C-treated cells with time compared with controls indicating attenuated de novo biosynthesis of these phospholipids. Addition of 1,2-dioctanoyl-sn-glycerol, a cell permeable 1,2-diacyl-sn-glycerol analog, to cells mimicked the inhibitory effect of phospholipase C on cardiolipin and phosphatidylglycerol biosynthesis from [1,3-3H]glycerol indicating the involvement of 1,2-diacyl-sn glycerol. The mechanism for the reduction in cardiolipin and phosphatidylglycerol biosynthesis in phospholipase C-treated cells appeared to be a decrease in the activities of phosphatidic acid:cytidine-5'triphosphate cytidylyltransferase and phosphatidylglycerolphosphate synthase, mediated by elevated 1,2-diacylsn-glycerol levels. Upon removal of phospholipase C from the incubation medium, phosphatidylcholine biosynthesis from [methyl-3H]choline was markedly stimulated. These data suggest that de novo phosphatidylglycerol and cardiolipin biosynthesis may be regulated by 1,2-diacyl-sn-glycerol and support the notion that phosphatidylglycerol and cardiolipin biosynthesis may be coordinated with phosphatidylcholine biosynthesis in H9c2 cardiac myoblast cells.
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PMID:On the mechanism of the phospholipase C-mediated attenuation of cardiolipin biosynthesis in H9c2 cardiac myoblast cells. 982 27