scholarly journals The involvement of phosphatidate phosphohydrolase and phospholipase A activities in the control of hepatic glycerolipid synthesis. Effects of acute feeding with glucose, fructose, sorbitol, glycerol and ethanol

1978 ◽  
Vol 174 (2) ◽  
pp. 667-670 ◽  
Author(s):  
R G Sturton ◽  
P H Pritchard ◽  
L Y Han ◽  
D N Brindley
Keyword(s):  
Single Dose ◽  
Microsomal Fraction ◽  
Phospholipase A ◽  
Stomach Tube ◽  
Triacylglycerol Synthesis ◽  
Phosphatidate Phosphohydrolase ◽  
Glycerolipid Synthesis ◽  
Significant Change ◽  
Hepatic Triacylglycerol

Rats were fed by stomach tube with a single dose of glucose, sorbitol, fructose, glycerol or ethanol of equivalent energy contents or with 0.15 M-NaCl. They were killed 6 h later and the relative rates of phosphatidate deacylation and dephosphorylation measured in the microsomal and supernatant fractions of the livers. Treatment with sorbitol, fructose, glycerol and ethanol increased phosphohydrolase activities in the microsomal and supernatant fractions. The only significant change in deacylase activity was an increase in the microsomal fraction produced by ethanol. It is proposed that hepatic triacylglycerol synthesis is partly controlled by the balance between phosphatidate phosphohydrolase and phospholipase A-type activities.

scholarly journals Effects of phenobarbital upon triacylglycerol metabolism in the rabbit

1980 ◽  
Vol 192 (1) ◽  
pp. 165-175 ◽  
Author(s):  
D M Goldberg ◽  
M W Roomi ◽  
A Yu ◽  
D A K Roncari
Keyword(s):  
Enzyme Induction ◽  
Microsomal Enzyme ◽  
Gamma Glutamyltransferase ◽  
Triacylglycerol Metabolism ◽  
Triacylglycerol Synthesis ◽  
Triacylglycerol Content ◽  
Phosphatidate Phosphohydrolase ◽  
Hepatic Triacylglycerol ◽  
Microsomal Enzyme Induction

1. The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male rabbits (2kg body wt.) injected intra-peritoneally with 50 mg of phenobarbital per kg for 10 days. 2. Occurrence of enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity and cytochrome P-450 content, as well as a doubling of microsomal protein per g of liver and a 54% increase in liver weight. Parallel increments in hepatic gamma-glutamyltransferase (EC 2.3.2.2) activity occurred; these were more pronounced in the whole homogenate than in the microsomes, which only accounted for 12.5% of the total enzyme activity in the controls and 17.0% in the animals given phenobarbital. Increased activity of gamma-glutamyltransferase activity was also observed in the blood serum of the test animals. 3. The rabbits given phenobarbital manifested increased hepatic triacylglycerol content and the triacylglycerol concentration of blood serum was also elevated. These changes were accompanied by a significantly enhanced ability of cell-free fractions of liver from the test animals (postmitochondrial supernatant and microsomal fractions) to synthesize glycerolipids in vitro from sn-[14C] glycerol 3-phosphate and fatty acids, when expressed per whole liver. Relative to the protein content of the fraction, glycerolipid synthesis in vitro was significantly decreased in the microsomes, presumably consequent upon the dramatic increase in their total protein content, whereas no change occurred in the postmitochondrial supernatant, possibly due to the protective effect of cytosolic factors present in this fraction and known to enhance glycerolipid synthesis. 4. Microsomal phosphatidate phosphohydrolase accounted for 85% of the total liver activity of this enzyme and its specific activity was 20-fold higher than that of the cytosolic phosphatidate phosphohydrolase (EC 3.1.3.4), when each was measured under optimal conditions. A significant increase in the activity of both enzymes per whole liver occurred in the rabbits given phenobarbital. A closer correlation between hepatic triacylglycerol content and and microsomal phosphatidate phosphohydrolase, as well as the above observation, suggest that this, rather than the cytosolic enzyme, may be rate-limiting for triacylglycerol synthesis in rabbit liver. 5. Significant correlations were observed between the various factors of hepatic microsomal-enzyme induction (aminopyrine N-demethylase and gamma-glutamyltransferase activity as well as cytochrome P-450 content) and hepatic triacylglycerol content, suggesting that that microsomal enzyme induction may promote hepatic triacylglycerol synthesis and consequently hypertriglyceridaemia in the rabbit.

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 effect of dietary carbohydrate and fat on the activities of some enzymes responsible for glycerolipid synthesis in rat liver

1978 ◽  
Vol 174 (2) ◽  
pp. 535-541 ◽  
Author(s):  
H P Glenny ◽  
M Bowley ◽  
S L Burditt ◽  
J Cooling ◽  
P H Pritchard ◽  
...  
Keyword(s):  
Corn Oil ◽  
Specific Activity ◽  
Male Rats ◽  
Dihydroxyacetone Phosphate ◽  
Triacylglycerol Synthesis ◽  
Choline Phosphotransferase ◽  
Phosphatidate Phosphohydrolase ◽  
Glycerolipid Synthesis ◽  
Starch Diet

1. Male rats were fed for 14 days on diets containing (by wt.) 53% of starch, or on diets in which 20% of the starch was replaced by sucrose, corn oil or lard. 2. The hepatic activities of the microsomal glycerol phosphate acyltransferase, dihydroxyacetone phosphate acyltransferase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase and choline phosphotransferase, and of the soluble phosphatidate phosphohydrolase, were measured. 3. The soluble phosphatidate phosphohydrolase activity was higher in those rats fed on lard than in those fed on the starch diet. Choline phosphotransferase activity was higher in the rats fed on corn oil than in those fed on the starch diet. 4. The rate of hepatic glycerolipid synthesis was measured in vivo 1 min after injection of [1,3-3H]glycerol and [1-14C]palmitate into the portal veins. 5. The relative rate of phosphatidylcholine synthesis in vivo was increased after feeding with corn oil and the higher specific activity of choline phosphotransferase may contribute to this result. The equivalent rate of triacylglycerol synthesis was increased by feeding with lard rather than corn oil, and the increased activity of phosphatidate phosphohydrolase may partly explain this. The latter changes probably contribute to the increased concentration of triacylglycerol which other authors have observed in the livers and sera of animals fed on saturated and monounsaturated fats.

scholarly journals Control of hepatic triacylglycerol synthesis. Diurnal variations in hepatic phosphatidate phosphohydrolase activity and in the concentrations of circulating insulin and corticosterone in rats

1979 ◽  
Vol 180 (2) ◽  
pp. 441-443 ◽  
Author(s):  
A M Knox ◽  
R G Sturton ◽  
J Cooling ◽  
D N Brindley
Keyword(s):  
Peak Concentration ◽  
Dark Period ◽  
Serum Insulin ◽  
Diurnal Variations ◽  
Male Rats ◽  
Serum Corticosterone ◽  
Triacylglycerol Synthesis ◽  
Phosphatidate Phosphohydrolase ◽  
Hepatic Triacylglycerol

Male rats were kept for 14 days with alternating 12h periods of light and darkness. The hepatic activity of soluble phosphatidate phosphohydrolase and the concentration of serum insulin were maximum at about 2h after dark. The peak concentration of serum corticosterone occurred 2h before the dark period. It is proposed that corticosterone is partly responsible for the increased phosphohydrolase activity, and that this enables the liver to increase its capacity to synthesize triacylglycerols during the period of maximum feeding.

scholarly journals Biosynthesis and secretion of triacylglycerol in rat liver after partial hepatectomy

1991 ◽  
Vol 277 (3) ◽  
pp. 723-728 ◽  
Author(s):  
L B Tijburg ◽  
C B Nyathi ◽  
G W Meijer ◽  
M J H Geelen
Keyword(s):  
Partial Hepatectomy ◽  
Rat Liver ◽  
Diacylglycerol Acyltransferase ◽  
Low Density Lipoproteins ◽  
Plasma Lipoproteins ◽  
Very Low Density Lipoproteins ◽  
Triacylglycerol Synthesis ◽  
Phosphatidate Phosphohydrolase ◽  
Hepatic Triacylglycerol

Partially hepatectomized rats were used to investigate the mechanism of fatty-liver development in the regenerating rat liver. After partial hepatectomy the amount of hepatic triacylglycerol increased by almost 4-fold compared with sham-operated rats. The activities of both cytosolic and microsomal phosphatidate phosphohydrolase were enhanced at 12 h after surgery. The activity of diacylglycerol acyltransferase was increased at a later stage of regeneration. Analysis of plasma lipoproteins showed a significant decrease of lipids associated with very-low-density lipoproteins (VLDL). Relative to control, the rate of hepatic triacylglycerol synthesis from [3H]glycerol in vivo was stimulated at 22 h after partial liver resection. However, secretion of glycerol-labelled triacylglycerol in VLDL was the same in control and hepatectomized rats. In cultures of hepatocytes from hepatectomized donor rats, the concentration of triacylglycerol and the biosynthesis of this lipid from [3H]glycerol or from [3H]oleate were enhanced. The secretion of total triacylglycerol into the medium was not affected, resulting in a net accumulation of intracellular triacylglycerol. The rate of secretion of leucine-labelled apolipoproteins B and E associated with VLDL was similar in cell cultures from hepatectomized and sham-operated rats. The results of this study show that the enhancement of the biosynthesis of triacylglycerol in hepatectomized livers is not accompanied by an increase of the secretion of VLDL.

Studies on the effects of magnesium ion and propranolol on iris muscle phosphatidate phosphohydrolase

1984 ◽  
Vol 62 (2-3) ◽  
pp. 170-177 ◽  
Author(s):  
Ata A. Abdel-Latif ◽  
Jack P. Smith
Keyword(s):  
Smooth Muscle ◽  
Divalent Cation ◽  
Microsomal Fraction ◽  
Specific Activity ◽  
Divalent Cations ◽  
Dependent Manner ◽  
Soluble Enzyme ◽  
Microsomal Enzyme ◽  
Time Intervals ◽  
Phosphatidate Phosphohydrolase

The properties, subcellular distribution, and the effects of Mg2+ and propranolol on phosphatidate phosphohydrolase (EC 3.1.3.4) from rabbit iris smooth muscle have been investigated. The particulate and soluble (0–30% (NH4)2SO4 fraction) enzymes were assayed using aqueous phosphatidate dispersions and membrane-bound phosphatidate as substrates, respectively. When measured with aqueous substrate, activity was detected in both the particulate and soluble fractions, with the highest relative specific activity found in the microsomal fraction. Maximum dephosphorylation by the microsomal enzyme was about 1100 nmol of inorganic phosphate released/h per milligram protein and occurred at pH 7.0–7.5. In general Mg2+ inhibited the phosphohydrolase activity of the microsomal fraction and stimulated that of the soluble fraction, and the effects of the divalent cation on both of these activities were reversed by propranolol. The microsomal enzyme was slightly stimulated by deoxycholate and inhibited by the divalent cations Mg2+, Ca2+, and Mn2+ at concentrations > 0.25 mM. In contrast, the soluble enzyme was stimulated by Mg2+. Inhibition of the microsomal enzyme by Mg2+ (0.5 mM) was reversed by both EDTA, which also stimulated at higher concentrations (1 mM), and propranolol (0.1–0.2 mM). The inhibitory effect of Ca2+ on the enzyme was not reversed by propranolol. In the absence of Mg2+, the microsomal enzyme was inhibited by propranolol in a dose-dependent manner, and both in the absence and presence of the divalent cation the soluble enzyme was inhibited by the drug in a similar manner. These data suggest that the cationic moiety of propranolol may act by competing at the Mg2+-binding sites. Addition of propranolol (0.2 mM) to iris muscle prelabelled with [14C]arachidonic acid increased accumulation of [14C]phosphatidic acid at all time intervals (2.5–90 min) and brought about a corresponding initial decrease in the formation of [14C]diacylglycerol at short time intervals (2.5 min), thus implicating the phosphohydrolase as a possible site of action of the drug on glycerolipid metabolism in this tissue. In addition to reporting on the characteristics and distribution of phosphatidate phosphohydrolase in the iris smooth muscle, the data presented add further support to our hypothesis that propranolol redirects glycerolipid metabolism in the iris by exerting multiple effects on the enzymes involved in their biosynthesis.

scholarly journals Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to particulate fractions of isolated rat hepatocytes

1984 ◽  
Vol 219 (3) ◽  
pp. 911-916 ◽  
Author(s):  
C Cascales ◽  
E H Mangiapane ◽  
D N Brindley
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Oleic Acid ◽  
Microsomal Fraction ◽  
Rat Hepatocytes ◽  
Total Activity ◽  
Cell Fractionation ◽  
Isolated Rat Hepatocytes ◽  
Phosphatidate Phosphohydrolase ◽  
Isolated Rat

The incubation of hepatocytes with 1-4mM-oleate increased the total activity of phosphatidate phosphohydrolase that was measured in the presence of Mg2+ to about 2-fold. This was accompanied by an increase in the proportion of the enzyme that was isolated with the particulate fractions. Conversely, the addition of up to 4mM-oleate decreased the recovery of phosphatidate phosphohydrolase in the cytosolic fraction from about 70% to 3% when hepatocytes were lysed with digitonin. Most of the increase in the membrane-associated phosphohydrolase activity was isolated after cell fractionation in the microsomal fraction that was enriched with the endoplasmic-reticulum marker arylesterase. It is proposed that the translocation of phosphatidate phosphohydrolase facilitates the increased synthesis of triacylglycerols in the liver when it is presented with an increased supply of fatty acids.

scholarly journals The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver

1978 ◽  
Vol 176 (3) ◽  
pp. 777-784 ◽  
Author(s):  
Helen P. Glenny ◽  
David N. Brindley
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Relative Rate ◽  
Male Rats ◽  
Very Low Density Lipoproteins ◽  
Triacylglycerol Synthesis ◽  
Phosphatidate Phosphohydrolase ◽  
Ethanol Feeding ◽  
Enzyme Adaptation ◽  
Subtotal Hepatectomy

1. Male rats were injected daily for 5 days with 0.15m-NaCl, corticotropin, cortisol or l-thyroxine and the rates of glycerolipid synthesis were measured in the livers after intraportal injection of [14C]palmitate and [3H]glycerol. 2. Injection of all three hormones decreased the rates of body-weight gain. 3. Cortisol treatment increased the weight of the liver relative to body weight. 4. Thyroxine treatment increased the relative rate of triacylglycerol synthesis from [3H]glycerol and decreased the relative accumulation of 3H and 14C in diacylglycerol. It did not significantly alter the accumulation of these isotopes in phosphatidate nor the activity of the soluble phosphatidate phosphohydrolase in the total liver. However, this activity increased by 1.5-fold when expressed relative to the soluble protein of the liver. The increased triacylglycerol synthesis appears to be related to a general increase in the turnover of fatty acids in the liver. 5. Treatment with cortisol and corticotropin increased the relative rate of triacylglycerol synthesis from [3H]glycerol, decreased the accumulation of 3H in phosphatidate and increased the flux of both isotopes from phosphatidate to diacylglycerol. This appeared to be caused by the increased activity of the soluble phosphatidate phosphohydrolase that was observed in the livers of the cortisol-treated rats. 6. It is proposed that cortisol could be directly or indirectly involved in increasing the activity of hepatic phosphatidate phosphohydrolase in starvation, diabetes, laparotomy, subtotal hepatectomy, liver damage, ethanol feeding and in obesity. This enzyme adaptation could contribute to the potential of the liver to increase its synthesis and accumulation of triacylglycerols or to secrete very-low-density lipoproteins.

Increased phosphatidic acid and decreased lysophosphatidic acid in response to thrombin is associated with inhibition of platelet aggregation

1993 ◽  
Vol 71 (9-10) ◽  
pp. 432-439 ◽  
Author(s):  
Jon M. Gerrard ◽  
Pauline Robinson ◽  
Michael Narvey ◽  
Archibald McNicol
Keyword(s):  
Platelet Aggregation ◽  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Human Platelet ◽  
Inhibitory Effect ◽  
Phospholipase A ◽  
Direct Role ◽  
Inhibition Of Platelet Aggregation ◽  
Phosphatidate Phosphohydrolase ◽  
Rule Out

Thromboxane A2, produced from the arachidonic acid released from platelet phospholipids by phospholipase A2, stimulates platelet aggregation. It remains unresolved whether additional products of platelet phospholipase A2 might promote aggregation. To address this question, we have used aspirin-treated platelets to block thromboxane A2 formation and studied the influence of the phospholipase A2 inhibitor U10029A on platelet aggregation and secretion in response to thrombin. U10029A at 100 μM markedly inhibited platelet aggregation, but had no effect on platelet secretion. Since this concentration of U10029A effectively blocked lysophosphatidic acid (LPA) formation, LPA was added and found to substantially reverse the inhibitory effect of U10029A in these platelets. Furthermore, the action of U10029A was not due to inhibition of phosphatidate phosphohydrolase because U10029A, unlike propranolol, did not inhibit this enzyme. Although it is not possible to conclusively rule out an effect of U10029A in addition to its inhibition of phospholipase A2, our results reveal that a product of phospholipase A2 other than thromboxane A2 is important for platelet aggregation, but not for secretion in response to thrombin. Our data suggest that this product is LPA. Since the amount of phosphatidic acid (PA) increased dramatically concurrent with inhibition of platelet aggregation, it is safe to conclude that PA has no direct role to promote platelet aggregation in response to thrombin.Key words: lysophosphatidic acid, phosphatidic acid, phospholipase A2, human platelet.

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