Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OFF products of horseradish peroxidase (EC 1.11.1.7)-catalyzed oxidation of p-phenetidine were isolated and reactive species were trapped with reduced glutathione (GSH) and butylated hydroxyanisole (BHA). When BHA was added to a reaction mixture after 5 min, subsequent TLC and mass spectrometric analysis revealed the formation of an adduct of BHA and 4-(ethoxyphenyl)-p-benzoquinone diimine (A). The diimine derivative (A) was unstable and its expected degradation products, 4-(ethoxyphenyl)-p-benzoquinone imine (B) and ammonia, were recovered from the reaction in stoichiometric amounts. Ethanol was an early product of the reaction presumably resulting from radical coupling reactions and its formation agreed with the combined production of A and B, suggesting that this was its sole route of formation. The addition of GSH to a reaction at various times and subsequent TLC and high performance liquid chromatographic analysis revealed the presence of at least seven conjugates. Two conjugates were identified by fast atom bombardment mass spectrometry, one as a mono-GSH conjugate of A and another as a mono-GSH conjugate of B. When purified [14C]B was mixed with [3H]GSH, three conjugates were isolated by high performance liquid chromatography, two of which were tentatively identified as di-GSH conjugates. The conjugates isolated existed in both oxidized and reduced forms which could be easily interconverted by redox processes. The production of such reactive species and their conjugates in vivo may be a useful indicator of peroxidase-catalyzed metabolism.
Mol Pharmacol 1985 Feb
PMID:Characterization and mechanism of formation of reactive products formed during peroxidase-catalyzed oxidation of p-phenetidine. Trapping of reactive species by reduced glutathione and butylated hydroxyanisole. 396 71

Ethanol and tryptophan have been demonstrated earlier to induce a rapid stimulation of hepatic ornithine decarboxylase (ODC) activity in overnight-fasted rats. In this study the effect of the administration of retinyl acetate prior to administering ethanol or tryptophan was investigated. The levels of ODC activity in the livers of control and experimental rats were assayed in vitro by measuring the release of 14CO2 from DL-[1-14C]ornithine. Intraperitoneal administration of retinyl acetate (1 microgram/100 g body wt) 1 hr before tube feeding ethanol (0.75 g as a 50% solution/100 g body wt) or L-tryptophan (30 mg in 3 ml water/100 g body wt) and 3 hr before killing caused an enhanced stimulation of hepatic ODC activity compared to that when each agent was administered alone. In vitro [14C]leucine incorporation into protein using hepatic microsomes of tryptophan-treated rats with or without retinyl acetate was increased in comparison with that of controls while decreases were observed when using microsomes of ethanol-treated rats with or without retinyl acetate. Although retinyl acetate has been reported earlier to inhibit the stimulation of hepatic ODC activity due to a variety of agents, including some agents known as carcinogens or promoters, it did not act in this manner against the acute administration of ethanol or tryptophan.
Exp Mol Pathol 1985 Aug
PMID:Hepatic ornithine decarboxylase activity in the rat as influenced by retinyl acetate and ethanol or tryptophan. 400 39

The influence of an acute exposure to ethanol on adenylyl cyclase activity in membrane fractions prepared from human corpus luteum was investigated. Ethanol up to a concentration of 5% (v/v) was without effect on basal luteal adenylyl cyclase activity, but markedly potentiated stimulation of NaF and hCG in a dose-dependent manner. In contrast, ethanol progressively inhibited forskolin stimulation at the same range of ethanol concentrations. Maximal NaF and hCG responsiveness of adenylyl cyclase activity was observed at 5% ethanol and reached values 80% and 100% higher than controls without ethanol, respectively. However, at the same ethanol concentration, forskolin-stimulated enzymatic activity was reduced by 40% relative to controls. Equilibrium binding studies involving [125I]hCG interaction with luteal membranes in the presence of the concentration of ethanol showing maximal hCG responsiveness indicated that ethanol slightly affected (15% increase) the hCG binding compared to controls, without any appreciable change on the Kd for the hormone. This minor effect of ethanol on gonadotropin binding sites contrasted greatly with the extent at which ethanol maximally potentiated the gonadotropin-stimulated adenylyl cyclase. GTP was found to be less effective than GMP-P(NH)P in sustaining ethanol potentiation, suggesting that ethanol is unlikely to act by inhibiting GTPase activity. These data indicate that the acute effects of ethanol inhibit forskolin-stimulated adenylyl cyclase at concentrations potentiating stimulatory effects of NaF and of hCG, and that the synergistic interaction of ethanol and gonadotropin stimulation of adenylyl cyclase is, at least in part, due to an increase in the functional coupling of the occupied hCG-receptor complex with the components of the enzyme system.
Mol Cell Endocrinol 1985 May
PMID:Opposite effects of ethanol on the activation of adenylyl cyclase in human corpus luteum membranes. 404 41

Synthase phosphatase, phosphorylase phosphatase and histone phosphatase activity in a leukocyte homogenate were found to have different sedimentation characteristics: both synthase phosphatase and phosphorylase phosphatase activity are associated with the microsomal fraction, while the majority of histone phosphatase activity (75-85%) was found in the cytosol. Synthase phosphatase, phosphorylase phosphatase and histone phosphatase activities accompanying the microsomal fraction are readily solubilized by 0.3% Triton X-100. When the solubilized microsomal enzymes were chromatographed on Sephadex G-200, the majority of synthase phosphatase, phosphorylase phosphatase and histone phosphatase activity migrated in single peaks corresponding to apparent molecular weights of 380 000, 250 000 and 68 000, respectively. A minor peak of 30 000, which had phosphatase activity against all three substrates was also obtained. Ethanol treatment resulted in solubilization and dissociation of the three phosphatase activities. It was found that although ethanol treatment resulted in a 4-fold increase of phosphorylase phosphatase activity, histone phosphatase activity was decreased (by 60%), while synthase phosphatase activity remained stable. Similar results were obtained when ethanol treatment was performed on the 17 000 X g supernatant. Chromatography of the ethanol-treated microsomes (or homogenate) on Sephadex G-200 showed that the phosphatase activity towards synthase D, phosphorylase a and phosphohistone coincided a Mr 30 000 species. Heat treatment of the Mr 30 000 peak resulted in dissociation of synthase phosphatase and phosphorylase phosphatase activity. Synthase phosphatase was inhibited by phosphorylase a in a kinetically non-competitive manner while histone phosphatase activity was not inhibited by synthase D (8.5 unit/ml) or by phosphorylase a (12 unit/ml).
Mol Cell Biochem 1984
PMID:Chromatographic characteristics and subcellular localization of synthase phosphatase, phosphorylase phosphatase and histone phosphatase in human polymorphonuclear leukocytes. 632 56

Rats were given ethanol chronically (20-30% of the energy) in a nutritionally sufficient diet regimen. Controls received lipid as an isoenergetic substitute for ethanol. Protein synthesis in hepatocytes isolated from ethanol-fed rats was decreased compared with controls, but not in isolated nonparenchymal liver cells. Ethanol added in vitro inhibited protein synthesis in hepatocytes by 30%, but not in nonparenchymal cells for both ethanol-fed and control rats. Protein export and protein degradation in isolated hepatocytes were not affected by long-term ethanol treatment. Isolated hepatocytes were separated according to their buoyant density in linear metrizamide gradients. They were distributed in a bell-shaped manner regardless of donor rat treatment. Cells of low density contained three times as much lipid as high density cells. They were probably enriched in periportal cells, since histologic examination indicated a predominantly periportal localization of cells containing lipid droplets. Distribution of the intra-acinar marker alanine aminotransferase supported this conclusion. Protein synthesis was similar in the low-density hepatocyte populations of the respective groups of rats, whereas it was inhibited in a high-density population of ethanol-treated rats compared to the controls. Inhibition of protein synthesis by 80 mM ethanol was lower in the low-density hepatocytes of ethanol-fed rats.
Exp Mol Pathol 1984 Aug
PMID:Ethanol effects on protein synthesis in nonparenchymal liver cells, hepatocytes, and density populations of hepatocytes. 646 35

Male Wistar rats were maintained for 35-40 days on a liquid diet containing 36% of calories as ethanol. Ethanol was replaced by carbohydrates in the isocaloric diet fed to control animals. The effect of ethanol consumption has been studied on the fluorescence polarization of rat liver plasma membranes and artificial lipid vesicles and on the lipid composition of the membranes. Fluorescence polarization in both membranes and vesicles was determined using DPH and TMA-DPH as fluorescence markers; from these data, the polarization term (ro/r-l)-1 and flow activation energy (delta E) were calculated. The ethanol consumption induces a more fluid environment within the membrane core of liver plasma membranes; the ethanol-fed rat membranes are more resistant to the in vitro effect of ethanol disordering the membrane structure. Vesicles obtained with lipids from either control membranes or ethanol-fed rat membranes were treated with ethanol and the changes in polarization paralleled to those exhibited by the membranes. The absence of phase transitions and of delta E changes was also shown in temperature-dependence studies. The lower cholesterol content found in ethanol-fed rat plasma membranes might be responsible for observed variations in the microviscosity.
Mol Cell Biochem 1984 Sep
PMID:The fluidity of plasma membranes from ethanol-treated rat liver. 649 25

In a previous study, a rat model of ethanol-induced pancreatic steatosis was developed in which chronic ethanol feeding resulted in a twofold increase in pancreatic cholesteryl ester content. The studies reported here were performed in order to elucidate the mechanism of this cholesteryl ester accumulation. Rats were pair fed ethanol or control diets for 3 weeks. Ethanol feeding resulted in an increased accumulation of serum cholesterol in the pancreas. Ethanol feeding also resulted in increased in vitro incorporation of labeled acetate and mevalonate into the sterol moiety of pancreatic cholesteryl ester and increased incorporation of labeled acetate into its fatty acid component. These results suggest that chronic ethanol feeding causes pancreatic cholesteryl ester accumulation by affecting exchange of cholesterol between serum and pancreatic tissue.
Exp Mol Pathol 1984 Dec
PMID:Chronic ethanol feeding causes accumulation of serum cholesterol in rat pancreas. 651 May 4

Weight paired (approximately 200 g) Long-Evans male rats (n = 48) were divided into two groups: an ethanol-consuming (A) and a water-consuming control (C) group. Ethanol concentration was raised incrementally over a one month period until it reached 25% (v/v). The diet of group C was regulated calorically to minimize differences between the two groups in the consumption of protein, fat, and carbohydrate. Half the members of each group were killed 12 weeks after initiating the special diets for the determination of myocardial electrolyte and water distributions and uptake of a tracer normally restricted to the extracellular space (ECS). The remaining rats were returned to a normal diet (recovery groups AR and CR) and killed 8 weeks later. Left ventricular tissue and plasma were analyzed for Na, K, Ca, and Mg; ECS was assessed in the same samples by tracer distribution and morphometric methods. Comparison of the myocardial [35S]sulfate space as a function of equilibration duration in the four groups indicates that the tracer leaks into the cellular compartment of alcoholic rats, suggesting that myocardial sarcolemmal permeability is increased in alcoholism. This interpretation is supported by the finding that all cations studied either were (Na, Ca) or tended to be (K, Mg) displaced down their respective electrochemical gradients. It is concluded that a reversible, non-selective sarcolemmal leakiness may be one of the earliest effects of alcoholism on the heart, eventually resulting in a redistribution of myocardial electrolytes and associated alterations of electrical, metabolic, and contractile activities.
J Mol Cell Cardiol 1983 Feb
PMID:In vivo effects of ethanol on the rat myocardium: evidence for a reversible, non-specific increase of sarcolemmal permeability. 685 57

The specific effect of ethanol on several aspects of the gel-to-liquid crystal transition of dipalmitoylphosphatidylcholine was investigated using two spectrophotometric techniques, one probe method and one direct method. Ethanol shifts the phase-transition temperature to low temperature, demonstrating that ethanol interacts preferentially with the fluid phase. Thermodynamic analysis of the melting point depression leads to a calculated membrane:buffer partition coefficient of 6.25 (mole fraction units) or 0.15 mole of ethanol per kilogram of lipid:mole of ethanol per liter of solution. Careful evaluation of the transition cooperativity with temperature resolution of +/- 0.1 degrees shows that there is no reduction in transition cooperativity, and thus no reduction in size of the cooperative lipid clusters due to ethanol. The implications of these findings for the mechanism of action of ethanol in terms of current theories of anesthetic mechanisms are discussed.
Mol Pharmacol 1982 Jul
PMID:The effects of ethanol on the thermotropic properties of dipalmitoylphosphatidylcholine. 689 3

Human erythrocytes were incubated with heat-inactivated plasma, and the transfer of cholesterol to the red cells was followed to equilibrium over 24 hr. When cholesterol-enriched plasma was used, there was a net flow of sterol into red cells. Ethanol, in a concentration-related manner, accelerated the cholesterol transfer without appreciably affecting the final sterol content of the erythrocytes at equilibrium. Ethanol also accelerated the exchange of tritiated cholesterol between normal or cholesterol-enriched plasma and red cells, whether or not there was a net cholesterol flow. Ethanol speeded up sterol transfer from several cholesterol donors, including prelabeled erythrocytes, low-density lipoproteins, high-density lipoproteins, and egg lecithin vesicles. Ethanol (0.35 M) increased the rate constant of the transfer by about 30-40% with different sterol donors. These observations may be related to the previously reported increase in cholesterol in the brain and red cell membranes of mice after chronic treatment with ethanol.
Mol Pharmacol 1982 May
PMID:Movement of free cholesterol from lipoproteins or lipid vesicles into erythrocytes. Acceleration by ethanol in vitro. 711 Jan 17


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