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PubMed1975

Inter-relations between the phospholipids of rat pancreatic islets during glucose stimulation, and their response to medium inositol and tetracaine.

1. Isolated rat pancreatic islets subjected to an increase in glucose concentration from 0.5 to 3 mg/ml showed an increased insulin secretion and 32P-labelling of their phospholipids, especially of phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, and CDP diglyceride. Neither fructose or inositol produced a similar effect. 2. The enhanced labelling of CDP diglyceride and phosphatidylglycerol was suppressed by adding inositol (0.1 mg/ml), while the phosphatidylinositol labelling was increased still further. 3. Tetracaine (0.5 mM), an antagonist of insulin secretion, inhi-ited phosphatidylinositol synthesis while phosphatidylglycerol, CDP diglyceride and phosphatidic acid formation were markedly increased. These effects on phospholipid synthesis were substantially reversed by adding inositol to the medium. Tetracaine also prevented the catabolism of phosphatidylinositol in prelabelled islets but this inhibiton was not reversed by inositol. 4. Inositol addition did not affect insulin secretion in glucose-stimulated islets nor secretion in tetracaine-treated islets. This need not exclude a possible role for heightened phosphatidylinositol cleavage in stimulated insulin secretion.

Animals↗
PubMed1983

Metabolism and intracellular distribution of a fluorescent analogue of phosphatidic acid in cultured fibroblasts.

We have shown that a fluorescent compound, C6-NBD-PA, behaves as an analogue for phosphatidic acid, an important intermediate in glycerolipid biosynthesis. This derivative is preferentially transferred from phospholipid vesicles to cultured Chinese hamster fibroblasts at 2 degrees C, while the C6-NBD-PA-derived fluorescence is localized at the nuclear membrane, endoplasmic reticulum, and mitochondria. Extraction and analysis of the fluorescent lipids associated with the cells after treatment with vesicles at 2 degrees C or 37 degrees C revealed that a large fraction of the fluorescent phosphatidic acid is converted to fluorescent diglyceride, phosphatidylcholine, and triglyceride. Although we do not yet know how accurately the metabolism and intracellular distribution of C6-NBD-PA and its metabolites reflect those of endogenous phosphatidic acid, it is encouraging that this fluorescent analogue is apparently metabolized through the diglyceride pathway to give fluorescent analogues of diglyceride, triglyceride, and phosphatidylcholine. This metabolism suggests that the presence of the fluorescent group on the acyl chain of the phosphatidic acid analogue does not inhibit the enzymes involved in phosphatidic acid metabolism. We conclude that fluorescent lipid analogues such as C6-NBD-PA may be useful in correlating biochemical studies of lipid metabolism with studies of the intracellular localization of lipid metabolites by fluorescence microscopy.

4-Chloro-7-nitrobenzofurazan↗
PubMed1982

Polar lipids in phototrophic bacteria of the Rhodospirillaceae and Chromatiaceae families.

The polar lipids of photosynthetic purple bacteria of the genera Chromatium, Thiocapsa, Thiocystis, Ectothiorhodospira, Rhodopseudomonas, Rhodospirillum, and Rhodomicrobium were analyzed. Characteristic compositions of the polar lipids were found for most of the Rhodospirillaceae and Chromatiaceae species. Phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin were the major phospholipids in most species. Phosphatidylcholine was present as a major component in all species of the genus Ectothiorhodospira, but was not detected in the remaining Chromatiaceae. It was also present in most of the Rhodospirillaceae species. No glycolipids were found in any of the Ectothiorhodospira species. In the Rhodospirillaceae, the glycolipids mono- and digalactosyl diglycerides were generally absent. Sulfoquinovosyl diglyceride was present in significant amounts in at least three species of the Rhodospirillaceae and may have been present in most of them, but only in traces. All of the Chromatiaceae species contained several glycolipids, one of which was similar to monogalactosyl diglyceride. Ornithine lipids were found in large amounts in most Rhodospirillaceae, but were absent in Ectothiorhodospira and in the other Chromatiaceae. The species examined could be divided into three groups on the basis of their lipid composition: (i) the genus Ectothiorhodospira; (ii) the remaining Chromatiaceae; and (iii) the Rhodospirillaceae. The data presented are compared with those available in the literature, and differences from other phototrophic organisms are discussed.

Chromatiaceae↗
PubMed1984

Biosynthesis of membrane-derived oligosaccharides: characterization of mdoB mutants defective in phosphoglycerol transferase I activity.

Phosphoglycerol transferase I, an enzyme of the inner, cytoplasmic membrane of Escherichia coli, catalyzes the in vitro transfer of phosphoglycerol residues from phosphatidylglycerol to membrane-derived oligosaccharides or to the model substrate arbutin (p-hydroxyphenyl-beta-D-glucoside). The products are a phosphoglycerol diester derivative of membrane-derived oligosaccharides or arbutin, respectively, and sn-1,2-diglyceride (B. J. Jackson and E. P. Kennedy, J. Biol. Chem. 258:2394-2398, 1983). Because this enzyme has its active site on the outer aspect of the inner membrane, it also catalyzes the transfer of phosphoglycerol residues to arbutin added to the medium (J.-P. Bohin and E. P. Kennedy, J. Biol. Chem. 259:8388-8393, 1984). When strains bearing the dgk mutation, which are defective in the enzyme diglyceride kinase, are grown in medium containing arbutin, they accumulate large amounts of sn-1,2-diglyceride, a product of the phosphoglycerol transferase I reaction. Growth is inhibited under these conditions. A further mutation in such a dgk strain, leading to the loss of phosphoglycerol transferase I activity, should result in the phenotype of arbutin resistance. We have exploited this fact to obtain strains with such mutations, designated mdoB, that map near min 99. Such mutants lack detectable phosphoglycerol transferase I activity, cannot transfer phosphoglycerol residues to arbutin in vivo, and synthesize membrane-derived oligosaccharides devoid of phosphoglycerol residues. These findings offer strong genetic support for the function of phosphoglycerol transferase I in membrane-derived oligosaccharide biosynthesis.

Alleles↗
PubMed1968

Fatty acid composition of the complex lipids of Staphylococcus aureus during the formation of the membrane-bound electron transport system.

In Staphylococcus aureus, 64 fatty acids could be separated by gas-liquid chromatography. The fatty acids consisted of normal, iso, and anteiso saturated fatty acids of from 10 to 21 carbon atoms. Of the total fatty acids, 2 to 4% were normal, iso, and anteiso monoenoic fatty acids. Positional isomers of the normal monoenoic fatty acids could be detected. The fatty acids could be extracted, leaving 1 to 2% of the total fatty acids in the residue. The proportions of the fatty acids in the residue and the total lipids differed significantly. The lipid extract contained less than 0.12% free fatty acid. Between 5 and 10% of the lipid fatty acids were associated with neutral lipids. The majority of the fatty acids were associated with the complex lipids: mono- and diglucosyl diglyceride, phosphatidyl glycerol, lysyl phosphatidyl glycerol, and cardiolipin. The proportions of the fatty acids changed markedly between bacteria grown anaerobically (no membrane-bound electron transport system) and those grown aerobically (containing a functional electron transport system). In each of the complex lipids, the proportions of the fatty acids, as well as the magnitude and direction of change in the molar quantity of the fatty acids per bacterium, changed dramatically between these growth conditions. Since the glucosyl diglycerides and phospholipids were formed from the same pool of diglyceride intermediates, the marked differences in fatty acids indicate that acyl transferase activities must be an important part of complex lipid metabolism in S. aureus.

Chromatography↗
PubMed1975

Inhibition of phosphatidylethanolamine biosynthesis in baby hamster kidney-21 cells infected with Semliki Forest virus.

Semliki Forest virus inhibits phosphatidylethanolamine biosynthesis in baby hamster kidney-21 cells 6 h after infection. Viral infection reduced the incorporation of [1,2-14C]-ethanolamine into intact cells by approximately 50%. A similar reduction in the activity of the ethanolaminephosphotransferase (EC 2.7.8.1) was also observed. The apparent Km for CDPethanolamine was 60 muM for the microsomal enzymes from infected or mock-infected cells. In addition, exogenous diglyceride only stimulated by 1.5-fold the ethanolaminephosphotransferase from virus- or mock-infected cells, whereas the same diglyceride preparations stimulated the cholinephosphotransferase (EC 2.7.8.2) from baby hamster kidney cells by sixfold. Generation of endogenous diglyceride by pretreatment of the microsomes with phospholipase C (EC 3.1.4.3) stimulated the activity of the cholinephosphotransferase but not the ethanolaminephosphotranferase. Semliki Forest virus does not inhibit all microsomal enzymes, since the activities of NADH- K3Fe(CN)6 reductase and NADH dehydrogenase (EC 1.6.99.3) were not affected. The ethanolaminephosphotransferase from virus- and mock-infected cells showed similar profiles of activity as a function of temperature; this result and other studies suggest that that membranous environment of the ethanolaminephosphotransferase was not significantly modified by the virus.

Cell Line↗
PubMed1994

Evidence that hepatic triglycerides provide acylglycerides for synthesis of bile phosphatidylcholines.

To determine the biochemical origin of bile phosphatidylcholines (PCs), rat liver perfusions with 16:1 fatty acid (FA) and [3H]glycerol were performed to generate novel radiolabeled bile and liver PCs and their hepatic glyceride precursors. Results showed total equilibration of bile and liver 16:1-16:1 PC when the specific activity of precursor glycerol-3-phosphate was kept constant. However, when the specific activity of glycerol-3-phosphate decreased during the labeling period and during a prolonged chase period with 17:1 FA and nonradiolabeled glycerol, the specific activity of bile 16:1-16:1 PC was appreciably higher than this same PC in the liver and during the chase period was even higher than its hepatic 16:1-16:1 acylglycerol precursors, phosphatidic acid and diglyceride. During the chase period with 17:1 FA, new radiolabeled 16:1-17:1 PC was formed, and again the specific activity of this PC in bile was greater than this PC and 16:1-17:1 phosphatidic acid and diglyceride in the liver. Only the specific activity of liver 16:1-16:1-(FA) triglyceride equaled or was high enough to support the formation of new bile 16:1-16:1 PC. These studies indicate that bile PCs do not directly derive from preexisting hepatic PCs or by de novo synthesis through phosphatidic acids and diglycerides, but likely originate by remodeling from a pool of hepatic triglycerides.

Animals↗
PubMed1970

The biosynthesis of phosphatidylinositol in human platelets.

Homogenates of human platelets can mediate the synthesis of phosphatidylinositol from myoinositol and cytidine diphosphate diglyceride. The cytidine diphosphate diglyceride: myoinositol, phosphatidyl transferase activity is particulate-bound, and the highest specific activity is found in the membrane fraction. The production of phosphatidylinositol is decreased by sulfhydryl-binding agents, and the addition of thiols to the platelet homogenates increases the enzymatic activity. The reaction exhibits a pH optimum of 8.5-9.0. Divalent cations stimulate the reaction, and manganous chloride was the most effective of those investigated. The K(m) of the enzyme for myoinositol is 0.27 mM, and the K(m) for cytidine diphosphate diglyceride is 0.53 mM. The enzymatic activity of platelets isolated from patients with several diseases known to interfere with platelet clotpromoting function is similar to the enzymatic activity of platelets from normal donors.

Blood Platelets↗
PubMed1988

Stimulation of in vitro triglyceride synthesis in the rat hepatocyte by growth hormone treatment in vivo.

Hepatic fatty acid metabolism in the rat is sexually differentiated. Rates of esterification by the liver of fatty acid into triglyceride and other esterification products (phospholipid, diglyceride, cholesteryl esters) are higher in the female than in the male. There is evidence to suggest that GH feminizes other hepatic systems that exhibit sexual dimorphism, including hepatic steroid metabolism, PRL receptors, and estrogen binding. To investigate the role of GH in maintenance of the high rates of fatty acid esterification observed in the female, we assessed rates of [1-14C]oleic acid utilization by hepatocytes prepared from hypophysectomized (hypox) cortisol/T3-replaced female rats with an without continuous in vivo infusion of human (h) GH (5 micrograms/h). In addition, we assessed the effect of in vivo hGH treatment (5 micrograms/h) on [1-14C]oleic acid utilization in the normal male rat. Hypophysectomy was accompanied by a reduction in incorporation of [1-14C]oleic acid into products of esterification (triglyceride, phospholipid, diglyceride) and oxidation (CO2, ketone bodies). Continuous infusion of hGH (5 micrograms/h; 14 days) restored rates of fatty acid esterification in the hypox-cortisol/T3-replaced female rat, with the exception of cholesteryl esters. hGH infusion partially restored rates of fatty acid oxidation in the hypox cortisol/T3-replaced female rat. Treatment of the adult male rat with continuous infusion of hGH (5 micrograms/h; 7 days) resulted in increased rates of incorporation of [1-14C] oleic acid into triglyceride. In contrast, incorporation of oleic acid into phospholipid, diglyceride, and cholesteryl esters was unaltered. These results suggest that GH may be an important regulator of hepatic fatty acid metabolism.

Animals↗
PubMed1988

Lymphatic absorption of hypolipidemic compound, 1-O-[p-(myristyloxy)-alpha-methylcinnamoyl] glycerol (LK-903).

The intestinal absorption process of 1-O-[p-(myristyloxy)-alpha-methylcinnamoyl] glycerol (LK-903), a new hypolipidemic compound, was studied in rats. When 3H-LK-903 or 3H-LKA [3H-p- (myristyloxy)-alpha-methyl cinnamic acid], labeled at the cinnamic acid moiety, or 14C-LK-903, labeled at the glycerol moiety, were administered orally to thoracic duct-cannulated rats at a dose of 0.233 mmol/kg, 31.1, 6.7 and 18.1% of the dose, respectively, appeared in the lymph within 24 h. In this case, radioactive compounds in the lymph lipids consisted of LKA (radioactivity was not detected in the fraction of LKA with 14C-LK-903), LK-903, diglyceride analogues and triglyceride analogues. The percentages of the triglyceride analogues were the highest, followed by the diglyceride analogues. On the other hand, when doubly labeled LK-903 (3H/14C = 1, corrected ratio) was administered orally, the values of 3H/14C for the monoglyceride, diglyceride and triglyceride analogues in the lymph were 1.2-1.5, 1.7-1.9 and 1.9-2.7, respectively. The lymphatic absorption of LK-903 was stimulated by the presence of lecithin but inhibited by a high dose of triolein. The results indicated that (1) LK-903 formed micelles in the intestine, (2) a large part of LK-903 was absorbed as such, (3) a part of LK-903 was hydrolyzed in the intestinal mucosa, and (4) a part of LKA formed by hydrolysis was again utilized to synthesize the higher glycerides and absorbed via the lymphatic absorption route for lipids.

Animals↗
PubMed1986

[Possible modes of action of growth factors and tumor promoters in the activation of the c-myc gene in Swiss 3T3 fibroblasts].

It has been suggested that the c-myc gene may play an important role in the regulation of cell proliferation. We have investigated the transmembrane signaling mechanisms of various growth factors and tumor promoters in Swiss 3T3 fibroblasts and have examined the causal relationship between these mechanisms and c-myc gene activation. Platelet-derived growth factor and FGF (fibroblast growth factor) induced the activation of diglyceride-protein kinase C and Ca2+ systems through phosphoinositide turnover, resulting in the activation of the c-myc gene. Epidermal growth factor did not activate these two systems but stimulated gene activation. Prostaglandin E1 elicited Ca2+ mobilization and cyclic AMP generation followed by c-myc gene activation. In contrast to these growth factors, tumor-promoting phorbol esters induced the direct activation of protein kinase C which led to c-myc gene expression. Bile acids, which are known to be colon tumor promoters, were inactive by themselves but enhanced FGF-induced diglyceride formation and thereby potentiated protein kinase C activation. It has not yet been examined whether bile acids potentiate FGF-induced activation of the c-myc gene. The growth factors described above and the phorbol esters stimulated DNA synthesis in the presence of insulin, whereas the bile acids potentiated FGF-induced DNA synthesis. These results strongly suggest that three messenger systems, diglyceride, Ca2+ and cyclic AMP, may be involved in c-myc gene activation which may be implicated in DNA synthesis in Swiss 3T3 cells.

Animals↗
PubMed1968

Lipid composition of chloroplasts isolated by aqueous and nonaqueous techniques.

Chloroplasts isolated from tobacco leaves in 0.5 M sucrose solution (the 1000 g pellet) contained 83% of the total cellular monogalactosyl diglyceride, 88% of the digalactosyl diglyceride, 76% of the sulfolipid, and 74% of the phosphatidyl glycerol. Phosphatidyl inositol was concentrated in the 15,000 g pellet. Phosphatidyl choline and phosphatidyl ethanolamine were concentrated in the 15,000 g supernatant fraction. Chloroplasts isolated from tobacco leaves by a nonaqueous technique in hexane-carbon tetrachloride show a glycerolipid composition similar to that found in chloroplasts isolated in the aqueous system, even though some lipid, particularly monogalactosyl diglyceride, is extracted by the organic solvent during the process.

Alkanes↗
PubMed1971

Biosynthesis of phosphatidylcholine by enzyme preparations from spinach leaves.

The enzymic incorporation of choline-1,2-(14)C from CDP-choline-1,2-(14)C into phosphatidylcholine by spinach leaf preparations was characterized. The enzyme catalyzing the incorporation, choline phosphotransferase, had a pH optimum of about 8.0 and required either Mn(2+) or Mg(2+) as cofactor. The saturation concentration of Mn(2+) was 0.3 mm and that for Mg(2+) was 13 mm. The K(m) for CDP-choline was 10 micro m. The choline phosphotransferase was inhibited by sulfhydryl reagents. The enzyme was inactivated at 30 degrees C, but this inactivation could be prevented by dithiothreitol and Mn(2+). Preincubation of the enzyme with Mn(2+) prevented inhibition by sulfhydryl reagents. The incorporation of diglyceride-U-(14)C into phosphatidylcholine was also studied. The enzyme did not show any diglyceride specificity when exogenous diglyceride was added, indicating that fatty acid distribution in phosphatidylcholine of spinach is not controlled by choline phosphotransferase.

Carbon Radioisotopes↗
PubMed1980

Membrane phospholipid synthesis in Escherichia coli. Cloning of a structural gene (plsB) of the sn-glycerol-3-phosphate acyl/transferase.

Si+ hybrid ColE1 plasmids of the Clarke-Carbon collection (Clarke, C., and Carbon, J. (1976) Cell 9, 91-99) which eliminate the sn-glycerol 3-phosphate growth requirement of a mutant of Escherichia coli with a Km defect in sn-glycerol-3-phosphate acyltransferase (plsB) were identified. Marked overproduction of a plasmid-encoded sn-glycerol-3-phosphate acyltransferase with a wild type Km in a host plsB- background indicates that the hybrid plasmids carry a structural gene for this enzyme. In addition, all of these plasmids suppress the phenotype of a mutation in a second locus involved in phospholipid biosynthesis, dgk (diglyceride kinase), and one of them also bears the dnaB structural gene. Diglyceride kinase activity is also overproduced in these strains. The linkage of plsB, dgk and dnaB loci was confirmed by transduction analysis which demonstrated the clockwise gene order malB, dnaB, dgk, plsB, and uvrA near Minute 91 on the E. coli linkage map. This is in contrast to the previously reported co-transduction of plsB with dctA near Minute 78 (Cronan, J. E., Jr., and Bell, R. M. (1974) J. Bacteriol., 120, 227-233). Recloning of restriction endonuclease fragments and in vitro mutagenesis have localized the dgk, and plsB loci to a 2.2-megadalton DNA segment, and have demonstrated that diglyceride kinase and sn-glycerol-3-phosphate acyltransferase activities reside in separate polypeptides. Availability of these clones and mutationally altered derivatives has allowed the identification of a single polypeptide (Mr = 83,000) corresponding to the sn-glycerol-3-phosphate acyltransferase and purification of this membrane-bound enzyme to near homogeneity (Larson, T. J., Lightner, V. A., Green, P. R., Modrich, P., and Bell, R. M. (1980) J. Biol. Chem. 255, 9421-9426). The size of the plsB polypeptide indicates that a major fraction of the DNA segment to which this gene has been localized is involved in coding for the sn-glycerol-3-phosphate acyltransferase.

Acyltransferases↗
PubMed1983

Interaction of sn-glycerol 3-phosphorothioate with Escherichia coli. In vitro and in vivo incorporation into phospholipids.

sn-Glycerol 3-phosphorothioate, a bacteriocidal analog of sn-glycerol 3-phosphate in strains of Escherichia coli with a functioning glycerol phosphate transport system, was investigated for its ability to be incorporated into phospholipid under in vitro and in vivo conditions. A cell-free particulate fraction from E. coli strain 8 catalyzes the transfer of sn-[3H]glycerol 3-phosphoro[35S]thioate to chloroform-soluble material in the presence of either CDP-diglyceride or palmitoyl coenzyme A. With CDP-diglyceride as the co-substrate, the product of the reaction was tentatively identified as phosphatidylglycerol phosphorothioate. No formation of phosphatidylglycerol was observed, suggesting that the specific phosphatase required for the synthesis of phosphatidylglycerol does not catalyze, or else at a greatly reduced rate, the hydrolysis of the phosphorothioate monoester linkage. The kinetics of incorporation of sn-[3H]glycerol 3-phosphate and phosphorothioate into chloroform-soluble material in the presence of CDP-diglyceride are almost identical. In the presence of palmitoyl coenzyme A, sn-[3H]glycerol 3-phosphoro[35S]thioate was converted to the phosphorothioate analog of phosphatidic acid. Kinetic analysis showed that the apparent Km values for the incorporation of the phosphate and the phosphorothioate derivatives into phospholipid were 0.4 and 0.8 mM, respectively. The Vmax for the phosphorothioate analog was approximately half that for the phosphate derivative. Chemically synthesized thiophosphatidic acid was not a substrate for CTP:phosphatidic acid cytidylyltransferase. sn-[3H]Glycerol 3-phosphoro[35S]thioate was incorporated into phospholipid by cultures of E. coli strain 8. The major phosphorothioate-containing phospholipid synthesized in vivo was identified as 1,2-diacyl-sn-[3H]glycerol 3-phosphoro[35S]thioate. The phosphorothioate analog of phosphatidylglycerol phosphate was not observed despite our observations that this analog can be synthesized in vitro. Our results indicate that the phosphorothioate analog is an effective sn-glycerol 3-phosphate surrogate and suggest that a major reason for its toxicity toward E. coli strain 8 may be due to a total blockade of endogenous phospholipid biosynthesis.

Chromatography, Ion Exchange↗
PubMed1994

Intracellular processes associated with vesicular transport from endoplasmic reticulum to Golgi and exocytosis: ethanol-induced changes in membrane biogenesis.

Membrane biogenesis, expressed in endoplasmic reticulum (ER) by formation of transport vesicles, was studied in the liver of ethanol-fed and pair-fed rats. In ER of ethanol-fed animals, the endogenous synthesis of phosphatidylcholine (PC) and its contribution to ER transport vesicles were reduced by 50%, as compared to that in pair-fed controls. Reduction of PC synthesis and of its presence in ER-transport vesicles was also observed in pair-fed controls when the native cytosol was replaced with that from ethanol-fed animals. In contrast, preincubation of ER membranes from ethanol-fed animals with cytosol from controls led to the stimulation of PC synthesis in ER and its contribution to ER-transport vesicles. Analysis of water soluble metabolites of [methyl-14C]choline phosphate revealed the accumulation of CDP-choline precursor in samples derived from ethanol-fed rats. Concomitantly, the endogenous synthesis of phosphatidylinositol (PI) in the ER of ethanol-fed animals was stimulated up to 400-500%, but declined when the cytosol from ethanol-fed rats was replaced with that from the controls. The restoration of PC synthesis, the normalization of PI synthase activity, and, similar to control, the contribution of PC to ER-transport vesicles in ethanol-fed animals was achieved when ER membranes were preincubated with diglycerides or the cytosol was treated with ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA). Conversely, addition of CaCl2-EGTA buffer containing 3 microM free Ca2+ to control samples, led to a reduction in PC synthesis. The studies on the effect of free Ca2+ on PI synthase and phosphatidic acid (PA) phosphatase activity established that in the presence of 1-3 microM free Ca2+, PI synthase activity remained constant, whereas that of PA phosphatase was reduced by 40% at 1 microM Ca2+, and no activity was detected when free Ca2+ was adjusted to 3 microM. The results suggest that modified membrane biogenesis in the liver of ethanol-fed rats is connected to the elevated free Ca2+ in the cytosol, which appears to regulate phosphatase activity. Accumulation of CDP-choline, decreased activity of PA phosphatase, and increased contribution of PI lipids to ER-transport vesicle membrane suggest that in ethanol-fed animals diglycerides are depleted and PA is utilized in a CDP-diacylglycerol pathway, thus leading to the generation of a different group of phospholipids and consequently modified ER-transport vesicle membrane.

Alcohol Drinking↗
PubMed1999

Release of glycosylphosphatidylinositol-anchored carboxypeptidase M by phosphatidylinositol-specific phospholipase C upregulates enzyme synthesis.

Carboxypeptidase M (CPM), a glycosylphosphatidylinositol (GPI)-anchored membrane protein, remained at a constant level in confluent Madin Darby canine kidney (MDCK) cells but was continually released into the medium in soluble form. The released CPM contained ethanolamine, indicating liberation by a phospholipase. Treatment of MDCK cells with 0.01 U/ml phosphatidylinositol-specific phospholipase C for 6 h led to a 5.5-fold increase in soluble CPM, yet the activity in cells remained constant, resulting in a 30% increase in total activity. The increase was due to new protein synthesis as evidenced by inhibition with 0.2 microM cycloheximide and a 63% increase in [35S]methionine incorporation into newly synthesized CPM. MDCK cells treated with 1-alkyl-2-acyl-glycerol, the diglyceride component of mammalian glycosylphosphatidylinositol anchors, exhibited a 36% increase in CPM activity, but diacylglycerols or phorbol esters were ineffective. Thus, release of GPI-anchored CPM can generate a diglyceride signal to replenish and maintain constant levels on the cell surface.

Animals↗
PubMed1988

In vitro and ex vivo effects of antidepressants on rat brain membrane-bound phosphatidylinositol synthetase activity.

The in vitro and ex vivo effects of antidepressant drugs on membrane-bound phosphatidylinositol (PI) synthetase and PI: myo-inositol exchange enzyme activities were examined. In rat brain subcellular fractions, PI synthetase occurred exclusively in the microsomes. In comparison, the activity of CDP-diglyceride independent PI:myo-inositol exchange enzyme was low (3%). Of the various CDP-diglycerides tested for the activation of PI synthetase, CDP-dipalmitin was the most active. Addition of 1 mM of desipramine, amitriptyline, imipramine, iprindole, clomipramine and mianserin in vitro significantly inhibited (30-60%) PI synthetase activity, whereas the same concentration of zimelidine and fluoxetine had no effect. At low liponucleotide concentrations, PI synthetase activity was significantly enhanced by imipramine (1 mM), whereas the enzyme activity was inhibited at higher liponucleotide concentrations (greater than 0.3 mM). In contrast, imipramine had no effect on the PI: myo-inositol exchange enzyme activity. No significant alteration in the PI synthetase activity was found following either acute (2 h) or chronic (21 d) treatment of rats with imipramine. The above results indicate that the de novo synthesis of PI is inhibited in vitro but not ex vivo by some antidepressant drugs. However, in view of the high concentration of the drugs required, the pharmacological significance of this inhibitory action with respect to their therapeutic effects is doubtful.

Animals↗