scholarly journals The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase

1977 ◽  
Vol 165 (3) ◽  
pp. 447-454 ◽  
Author(s):  
M Bowley ◽  
J Cooling ◽  
S L Burditt ◽  
D N Brindley
Keyword(s):  
Physical Properties ◽  
Rat Liver ◽  
Partition Coefficients ◽  
Inorganic Cations ◽  
Cationic Drugs ◽  
Phosphatidate Phosphohydrolase ◽  
Glycerolipid Synthesis

1. Phosphatidate phosphohydrolase from the particle-free supernatant of rat liver was assayed by using emulsions of phosphatidate as substrate. 2. The inhibition of the phosphohydrolase by chlorpromazine was of a competitive type with respect to phosphatidate. The potency of various amphiphilic cationic drugs as inhibitors of this reaction was related to their partition coefficients into a phosphatidate emulsion. 3. The effect of chlorpromazine on the phosphohydrolase activity was complementary rather than antagonistic towards Mg2+. Chlorpromazine stimulated the phosphohydrolase activity in the absence of added Mg2+ and was able to replace the requirement for Mg2+. However, at optimum concentrations of Mg2+, chlorpromazine inhibited the reaction, as did Ca2+. The phosphohydrolase activity was also stimulated by Co2+ and to a lesser extent by Mn2+, Fe2+, Fe3+, Ca2+, spermine and spermidine when Mg2+ was not added to the assays. 4. It is concluded that the inhibition of phosphatidate phosphohydrolase by amphiphilic cations can largely be explained by the interaction of these compounds with phosphatidate, which changes the physical properties of the lipid, making it less available for conversion into diacylglycerol. 5. The implications of these results to the effects of amphiphilic cations in redirecting glycerolipid synthesis at the level of phosphatidate are discussed.

scholarly journals The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver

1977 ◽  
Vol 168 (2) ◽  
pp. 147-153 ◽  
Author(s):  
P H Whiting ◽  
M Bowley ◽  
R G Sturton ◽  
P H Pritchard ◽  
D N Brindley ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Single Dose ◽  
Rat Liver ◽  
Diacylglycerol Acyltransferase ◽  
Diabetic Rats ◽  
Glycerol Phosphate ◽  
Choline Phosphotransferase ◽  
Phosphatidate Phosphohydrolase ◽  
Glycerolipid Synthesis ◽  
Increased Activity

1. Rats were injected with a single dose of 35mg of streptozotocin/kg body wt. They exhibited a diabetes that was characterized by glycosuria, polyuria, polydipsia, hyperphagia, hyperglycaemia, increased concentrations of unesterified fatty acids, glycerol and triacylglycerols in the serum and an increased activity of glucose 6-phosphatase in the liver. 2. After 10 weeks the hepatic activities of the microsomal glycerol phosphate acyltransferase, phosphatidate phosphohydrolase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase, choline phosphotransferase, CDP-diacylglycerolx—inositol phosphatidyltransferase and the soluble phosphatidate phosphohydrolase were measured. 3. The only significant changes were an increase in the activity of the soluble phosphatidate phosphohydrolase and a decrease in that of the CDP-diacylglycerol—inositol phosphatidyltransferase in the diabetic rats. 4. These results are discussed in relation to the control of glycerolipid synthesis.

scholarly journals The effects of acute ethanol feeding and of chronic benfluorex administration on the activities of some enzymes of glycerolipid synthesis in rat liver and adipose tissue

1977 ◽  
Vol 166 (3) ◽  
pp. 639-642 ◽  
Author(s):  
P H Pritchard ◽  
M Bowley ◽  
S L Burditt ◽  
J Cooling ◽  
H P Glenny ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Rat Liver ◽  
Energy Content ◽  
Phosphatidate Phosphohydrolase ◽  
Acute Ethanol ◽  
Ethanol Feeding ◽  
Glycerolipid Synthesis

Rats were treated for 5 days with benfluorex [1-(3-trifluoromethylphenyl)-2-[N-(2-benzoyloxyethyl)amino]propane] or with suspending medium (controls). They were then intubated with an acute intoxicating dose of ethanol or with glucose of equivalent energy content. Treatment of the control rats with ethanol specifically increases the hepatic activity of the soluble phosphatidate phosphohydrolase by about 5-fold in 6 h. The equivalent increase for the benfluorex-treated rats were about 2-fold. The results are discussed in relation to the effects of ethanol and benfluorex on glycerolipid synthesis.

scholarly journals Drugs affecting the synthesis of glycerides and phospholipids in rat liver. The effects of clofibrate, halofenate, fenfluramine, amphetamine, cinchocaine, chlorpromazine, demethylimipramine, mepyramine and some of their derivatives

1975 ◽  
Vol 148 (3) ◽  
pp. 461-469 ◽  
Author(s):  
D N Brindley ◽  
M Bowley
Keyword(s):  
Rat Liver ◽  
Inhibitory Effect ◽  
Diacylglycerol Acyltransferase ◽  
Major Effect ◽  
Glycerol Phosphate ◽  
Liver Slices ◽  
Phosphatidate Phosphohydrolase ◽  
Marked Accumulation ◽  
Glycerolipid Synthesis ◽  
Phosphatidylcholine Synthesis

The effects on glycerolipid synthesis of a series of compounds including many drugs were investigated in cell-free preparations and slices of rat liver. p-Chlorobenzoate, p-chlorophenoxyisobutyrate, halofenate, D-amphetamine, adrenaline, procaine and N-[2-(4-chloro-3-sulphamoylbenzoyloxy)ethyl]norfenfluramine had little inhibitory effect on any of the systems investigated. Two amphiphilic anions, clofenapate and 2-(p-chlorophenyl)-2-(m-trifluoromethylphenoxy)acetate, both inhibited glycerol phosphate acyltransferase and diacylglycerol acyltransferase at approx. 1.6 and 0.7 mm respectively. Clofenapate (1 mm) also inhibited the incorporation of glycerol into lipids by rat liver slices without altering the relative proportions of the different lipids synthesized. The amphilic amines, mepyramine, fenfluramine, norfenfluramine, hydroxyethylnorfenfluramine, N-(2-benzoyloxyethyl)norfenfluramine, cinchocaine, chlorpromazine and demethylimipramine inhibited phosphatidate phosphohydrolase by 50% at concentrations between 0.2 and 0.9 mm. The last four compounds inhibited glycerol phosphate acyltransferase by 50% at concentrations between 1 and 2.6 mm. None of the amines examined appeared to be an effective inhibitor of diacylglycerol acyltransferase. Norfenfluramine, hydroxyethylnorfenfluramine and N-(2-benzoyloxyethyl)norfenfluramine produced less inhibition of glycerol incorporation into total lipids than was observed with equimolar clofenapate. The major effect of these amines in liver slices was to inhibit triacylglycerol and phosphatidylcholine synthesis and to produce a marked accumulation of phosphatidate. The results are discussed in terms of the control of glycerolipid synthesis. They partly explain the observed effects of the various drugs on lipid metabolism. The possible use of these compounds as biochemical tools with which to investigate the reactions of glycerolipid synthesis is considered.

scholarly journals Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. The effects of chlorpromazine, demethylimipramine, cinchocaine, norfenfluramine, mepyramine and magnesium ions

1977 ◽  
Vol 162 (1) ◽  
pp. 25-32 ◽  
Author(s):  
R G Sturton ◽  
D N Brindley
Keyword(s):  
Rat Liver ◽  
Threshold Concentration ◽  
Transferase Activity ◽  
Bivalent Cation ◽  
Cationic Drugs ◽  
Phosphatidate Phosphohydrolase ◽  
Microsomal Membranes ◽  
Acidic Phospholipids ◽  
Simultaneous Synthesis ◽  
High Concentrations

1. Microsomal membranes from rat liver were incubated with ATP, CoA, Mg2+, [14C]palmitate, F- and sn-glycerol 3-phosphate in order to label them with [14C]phosphatidate. These membranes were isolated and used in a second incubation in which [3H]CTP was present, and the simultaneous synthesis of [14C]diacylglycerol and [3H]CDP-diacylglycerol was measured. 2. The addition of phosphatidate phosphohydrolase, which had been partially purified from the particle-free supernatant, supplemented the activity of the endogenous phosphohydrolase, but it did not alter the rate of CDP-diacylglycerol formation. 3. Adding EDTA inhibited phosphatidate cytidylyl-transferase activity and stimulated the activity of the phosphohydrolases by removing excess of Mg2+. 4. Increasing the concentration of Mg2+, norfenfluramine or chlorpromazine in the assay system stimulated cytidylyltransferase activity, but decreased the activities of both phosphohydrolases. 5. The mechanism for the stimulation of cytidylyl=transferase activity by the cationic drugs and Mg2+ was investigated with emulsions of phosphatidate and the microsomal fraction of rat liver. 6. There was a threshold concentration of about 5mM-MgCl2 below which no cytidylyltransferase activity was detected in the presence or absence of norfenfluramine. Just above this threshold concentration norfenfluramine stimulated cytidylyltransferase activity, but this stimulation disappeared as the Mg2+ concentration was raised to its optimum of 20mM. Norfenfluramine therefore partially replaced the bivalent-cation requirement. 7. At 30 mM-MgCl2 amphiphilic cationic drugs inhibited cytidylyltransferase activity at relatively high concentrations in a non-competitive manner with respect to phosphatidate. 8. The implications of these results are discussed with respect to the regulation of the synthesis of the acidic phospholipids compared with the synthesis of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol.

Phase Behavior and Physical Properties of Dimethyl Ether/Water/Heavy-Oil Systems Under Reservoir Conditions

SPE Journal ◽  
2021 ◽  
pp. 1-17
Author(s):  
Desheng Huang ◽  
Ruixue Li ◽  
Daoyong Yang
Keyword(s):  
Physical Properties ◽  
Phase Behavior ◽  
Dimethyl Ether ◽  
Heavy Oil ◽  
Partition Coefficients ◽  
Binary Interaction ◽  
Binary Interaction Parameter ◽  
Translation Strategy ◽  
Wide Range ◽  
Oil Mixtures

Summary Phase behavior and physical properties including saturation pressures, swelling factors (SFs), phase volumes, dimethyl ether (DME) partition coefficients, and DME solubility for heavy-oil mixtures containing polar substances have been experimentally and theoretically determined. Experimentally, novel phase behavior experiments of DME/water/heavy-oil mixtures spanning a wide range of pressures and temperatures have been conducted. More specifically, a total of five pressure/volume/temperature (PVT) experiments consisting of two tests of DME/heavy-oil mixtures and three tests of DME/water/heavy-oil mixtures have been performed to measure saturation pressures, phase volumes, and SFs. Theoretically, the modified Peng-Robinson equation of state (EOS) (PR EOS) together with the Huron-Vidal mixing rule, as well as the Péneloux et al. (1982)volume-translation strategy, is adopted to perform phase-equilibrium calculations. The binary-interaction parameter (BIP) between the DME/heavy-oil pair, which is obtained by matching the measured saturation pressures of DME/heavy-oil mixtures, works well for DME/heavy-oil mixtures in the presence and absence of water. The new model developed in this work is capable of accurately reproducing the experimentally measured multiphase boundaries, phase volumes, and SFs for the aforementioned mixtures with the root-mean-squared relative error (RMSRE) of 3.92, 9.40, and 0.92%, respectively, while it can also be used to determine DME partition coefficients and DME solubility for DME/water/heavy-oil systems.

scholarly journals Further Evidence on the Intramolecular Lactonization in Rat Liver Microsomal Metabolism of 12-O-acetylated Retronecine-type Pyrrolizidine Alkaloids

2013 ◽  
Vol 8 (11) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Jun Tang ◽  
Zhengtao Wang ◽  
Teruaki Akao ◽  
Masao Hattori
Keyword(s):  
Physical Properties ◽  
Spectral Data ◽  
Rat Liver ◽  
Pyrrolizidine Alkaloids ◽  
Pyrrolizidine Alkaloid ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Microsomal Metabolism ◽  
Chromatographic Methods ◽  
Transformation Pathway

We have previously found evidence of intramolecular lactonization in rat liver microsomal metabolism of isoline, a 12- O-acetylated pyrrolizidine alkaloid. In this study, the metabolism of another 12- O-acetylated pyrrolizidine alkaloid, acetylduciformine, by the proposed transformation pathway was investigated under the same incubation conditions. Two deacetylated metabolites from acetylduciformine were isolated and purified by chromatographic methods, and further characterized based on their physical properties and spectral data. One metabolite (lankongensisine A) was the lactone of another one (duciformine). Both compounds were first obtained as hydrolyzed metabolites from acetylduciformine by rat liver microsomes. More importantly, the present study provided further evidence for the intramolecular lactonization in the microsomal metabolism of 12- O-acetylated retronecine-type PAs.

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