Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relation between Ca2+ efflux, Ca2+ mobilization from mitochondria and glycogenolysis was studied in perfused euthyroid and hypothyroid rat livers stimulated by Ca2+-mobilizing hormones. Ca2+ efflux, induced by noradrenaline (1 microM) in the absence or presence of DL-propranolol (10 microM) from livers perfused with medium containing a low concentration of Ca2+ (approx. 24 microM), was decreased by more than 50% in hypothyroidism. This correlated with an equal decrease of the fractional mobilization of mitochondrial Ca2+, which could account for 65% of the difference between the net amounts of Ca2+ expelled from the euthyroid and hypothyroid livers. With vasopressin (10 nM) similar results were found, suggesting that hypothyroidism has a general effect on mobilization of internal Ca2+. In normal Ca2+ medium (1300 microM), however, the effect of vasopressin on net Ca2+ fluxes and phosphorylase activation was not impaired in hypothyroidism, indicating that Ca2+ mobilization from the mitochondria in this case plays a minor role in phosphorylase activation. The alpha 1-adrenergic responses of Ca2+ efflux, phosphorylase activation and glucose output, glucose-6-phosphatase activity and oxygen consumption in hypothyroid rat liver were completely restored by in vivo T3 injections (0.5 micrograms per 100 g body weight, daily during 3 days). Perfusion with T3 (100 pM) during 19 min did not influence hypothyroid rat liver oxygen consumption and alpha 1-receptor-mediated Ca2+ efflux. However, this in vitro T3 treatment showed a completely recovered alpha 1-adrenergic response of phosphorylase and a partly restored glucose-6-phosphatase activity and glucose output. The results indicate that thyroid hormones may control alpha 1-adrenergic stimulation of glycogenolysis by at least two mechanisms, i.e., a long-term action on Ca2+ mobilization, and a short-term action on separate stages of the glycogenolytic process.
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PMID:Effect of thyroid hormone on intracellular Ca2+ mobilization by noradrenaline and vasopressin in relation to glycogenolysis in rat liver. 299 6

Alterations of catalytic activities of the microsomal glucose-6-phosphatase system were examined following either ferrous iron- or halothane (CF3CHBrCl) and carbon tetrachloride (CCl4) free-radical-mediated peroxidation of the microsomal membrane. Enzyme assays were performed in native and solubilized microsomes using either glucose 6-phosphate or mannose 6-phosphate as substrate. Lipid peroxidation was assessed by the amounts of malondialdehyde equivalents formed. Regardless of whether the experiments were performed in the presence of NADPH/Fe3+, NADPH/CF3CHBrCl, or NADPH/CCl4, with the onset of lipid peroxidation, mannose-6-phosphatase activity of the native microsomes increased immediately, while further alterations in catalytic activities were only detectable when lipid peroxidation had passed characteristic threshold values: above 2 nmol malondialdehyde/mg microsomal protein, glucose-6-phosphatase activity of the native microsomes was lost, and at 10 nmol malondialdehyde/mg microsomal protein, glucose-6-phosphatase and mannose-6-phosphatase activity of the solubilized microsomes started to decline. It is concluded that the latter alterations are due to an irreversible damage of the phosphohydrolase active site of the glucose-6-phosphatase system, while the changes observed at earlier stages of microsomal lipid peroxidation may also reflect alterations of the transporter components of the glucose-6-phosphatase system. Virtually no changes in the catalytic activities of the glucose-6-phosphatase system occurred under anaerobic conditions, indicating that CF3CHCl and CCl3 radicals are without direct damaging effect on the glucose-6-phosphatase system. Further, maximum effects of carbon tetrachloride and halothane on lipid peroxidation and enzyme activities were observed at an oxygen partial pressure (PO2) of 2 mmHg, providing additional evidence for the crucial role of low PO2 in the hepatotoxicity of both haloalkanes.
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PMID:Alterations of the microsomal glucose-6-phosphatase system evoked by ferrous iron- and haloalkane free-radical-mediated lipid peroxidation. 300 50

Previous studies have demonstrated that sera from patients with severe liver damage after halothane anesthesia ("halothane hepatitis") contain antibodies reacting with novel antigenic determinants expressed on hepatocytes from rabbits exposed previously to halothane. To determine the structure of the halothane-induced antigen(s), immunoblotting experiments were performed using patient sera and rabbit liver subcellular fractions. Three polypeptide antigens (Mr 100,000, 76,000 and 57,000) expressed in liver fractions from animals sacrificed 16 hr after exposure to 1% halothane in oxygen for 45 min, but not in fractions from unexposed animals, were identified. Analysis of fractions prepared by differential and sucrose density gradient centrifugation, and characterized by enzyme marker analysis, localized all three antigens to a microsomal subfraction relatively enriched in glucose-6-phosphatase activity, therefore, presumably derived from the endoplasmic reticulum. Antibodies to these antigens were detected in 19 of 24 sera from patients with halothane hepatitis, and four distinct patterns of antibody specificity were observed: 100,000 + 76,000 (seven patients), 100,000 alone (seven patients), 76,000 alone (three patients) and 57,000 alone (two patients). Such antibodies were not detectable in sera from 24 normal blood donors or 36 control patients. Thus, halothane induces expression of three distinct polypeptide antigens in liver, and patients with halothane hepatitis differ in patterns of recognition of these antigens by circulating antibodies.
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PMID:Identification by immunoblotting of three halothane-induced liver microsomal polypeptide antigens recognized by antibodies in sera from patients with halothane-associated hepatitis. 330 10

The study was designed to examine the effect of feeding a purified versus a cereal-based closed formula (control) diet on toxicity to carbon tetrachloride or oxygen. Twenty-eight-day-old male ICR mie were fed a purified or cereal-based closed formula diet for 14 or 84 days. After treatment with carbon tetrachloride or exposure to a 100% oxygen atmosphere, survival time and percentage survival were the same for mice fed either diet. In both dietary groups, carbon tetrachloride injection caused a similar decrease in hepatic nonprotein sulfhydryl compounds and glucose-6-phosphatase activity. It was concluded that, unlike previous findings with the herbicide paraquat, toxicity to carbon tetrachloride or oxygen is not increased by feeding a purified diet compared to a closed formula diet. The results provided further evidence to suggest that a free radical-lipid peroxidation process may not be the primary mechanism of the toxic effects of paraquat.
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PMID:Lack of effect of a purified diet on carbon tetrachloride or oxygen toxicity. 609 88

Anaerobic in vitro incubation of microsomes from phenobarbital(PB)-induced rats with halothane results in an irreversible decrease of measurable cytochrome P-450. There is a parallel decrease in heme content under the same incubation conditions. However, microsomes from 3-methylcholanthrene(3-MC)-induced or untreated animals do not show a reduction in cytochrome P-450 content. Aerobic incubation with halothane results in a decrease of cytochrome P-450 which can be completely reversed by dialysis or the addition of potassium ferricyanide. These latter treatments only partially restore the cytochrome P-450 levels following anaerobic incubations. The decrease in cytochrome caused by halothane is not associated with measureable heme N-alkyl adduct formation; lipid peroxidation does not play a role as indicated by the lack of effect of 1 mM EDTA or a decrease in glucose-6-phosphatase activity. Halothane metabolites are bound irreversibly to microsomal protein as determined by gel electrophoresis only when the oxygen concentration is very low. The mechanism of cytochrome P-450 decrease is consistent with the formation of a reactive metabolite which binds to the protein portion and also destroys heme.
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PMID:Cytochrome P-450 and halothane metabolism. Decrease in rat liver microsomal P-450 in vitro. 687 91

We recently reported (Acta Paediatr Scand 1992;8: 580-4) three preterm infants with severe respiratory distress syndrome and abnormal glucose profiles for the first 5 days of life who subsequently died in infancy; only at autopsy were they shown to have abnormal glucose-6-phosphatase activity. We have therefore studied retrospectively in a matched cohort of 109 infants the blood glucose profiles correlated with the severity of respiratory distress syndrome (expressed as the fraction of inspired oxygen, FiO2): group A, mild, FiO2 < 0.25; group B, moderate, FiO2 0.26-0.50; group C, severe, FiO2 > 0.51. All groups had a similar frequency of low blood glucose values (15% < or = 2.2 mmol/L; 29% < or = 2.6 mmol/L), but high blood glucose values and greater variability in glucose values were more common in groups B and C despite lower caloric intakes (A, 4.3%; B, 9.3%; C, 9.6% > or = 7 mmol/L). We conclude that the early blood glucose patterns in those three previously described preterm infants with abnormal hepatic glucose-6-phosphatase activity at autopsy cannot be viewed as abnormal when considered against a matched cohort of infants. Preterm infants at risk of genetic or developmental delays in blood glucose homeostasis should be reassessed after recovery from their acute illnesses.
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PMID:Early detection of metabolic abnormalities in preterm infants impaired by disorders of blood glucose concentrations. 814 5

The anti-cancer efficacy of dietary beta-carotene (BC, 120 mg/kg diet, daily) was evaluated during diethylnitrosamine (DEN, 200 mg/kg body weight)-induced hepatocarcinogenesis in male Sprague-Dawley rats. BC treatment was carried out throughout the study, before initiation or selection/promotion phase of hepatocarcinogenesis in a defined experimental protocol. In red blood cells (RBC) and microsomal fractions from hepatic nodular and non-nodular surrounding parenchyma, the enzymatic lipid peroxidation increased significantly by more than 3-fold, 9- to 10-fold and 4- to 7-fold respectively 18 weeks following initiation by DEN as compared to normal control animals. RBC membrane protein damage was estimated by alanine release and was found to increase more than 5-fold in the same time period in DEN control rats. A decrease in hepatic cytosolic and microsomal glucose-6-phosphatase activities was observed, whereas the activities of the oxygen-derived free-radical scavenger enzymes, like cytosolic catalase and superoxide dismutase, were shown to increase significantly at the same time point. However, BC exposure in the different phases to hepatocarcinogenesis substantially changed all the above parameters in limiting the action of DEN. Results showed that the most significant beneficial effect of BC during hepatocarcinogenesis was exerted mainly in long term continuous and/or the initiation phase of carcinogenicity, rather than in the selection/promotion phase. Moreover, the volumetric and numerical densities of the preneoplastic lesions were all appreciably reduced by exposure to BC. We conclude that long term intake of BC could reduce cancer risk by preventing hepatic lipid peroxidation and RBC membrane protein damage due to its antioxidant actions.
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PMID:Beta-carotene prevents lipid peroxidation and red blood cell membrane protein damage in experimental hepatocarcinogenesis. 859 Apr 36

Polymorphonuclear neutrophils play an important role against pathogens through the production of toxic oxygen metabolites by the NADPH oxidase enzyme, which reduces oxygen to superoxide anion in the respiratory burst. Neutropenia, infectious complications and impaired neutrophil function are often reported in glycogen storage disease type Ib (GSDIb), a metabolic disorder characterized by increased glycogen and decreased glucose-6-phosphatase (G-6-P) activity in the liver. Two children with GSDIb and associated neutropenia with recurrent bacterial infections were treated daily with different doses of rHu-GM-CSF. NADPH oxidase activity and chemotaxis in patients were assessed before and during therapy in stimulated and unstimulated neutrophils. During rHu-GM-CSF treatment, any increase found in the NADPH oxidase activity of patients was not significant with respect to that in controls. In one patient chemotaxis was greater than of controls. This finding suggests that in patients with GSDIb both neutropenia and PMN abnormalities may be responsible for infections, and PMN dysfunction probably depends on the degree of inherited functional G-6-P deficit.
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PMID:NADPH oxidase activity and chemotaxis by neutrophils in two patients with glycogen storage disease type Ib treated with recombinant human granulocyte-monocyte colony-stimulating factor. 864 44

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with 99mTc. When this 99mTc-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment.
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PMID:Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin using rat hepatic microsomes as model membranes. 905 55

This study was designed to investigate the possible oxidative changes associated with alterations in cytochrome P450 levels in rat liver. Accordingly, extent of peroxidative processes, cytochrome and antioxidant content, capacity to face an oxidative stress were determined in liver microsomes, mitochondria, and homogenates from normal and phenobarbital (PB)-treated rats. Liver content of microsomal and mitochondrial proteins was also determined by the values of the activities of marker enzymes (glucose-6-phosphatase and cytochrome oxidase, respectively) in liver homogenate and in two cellular fractions. The increase in the liver content of microsomal and mitochondrial proteins indicated that PB caused proliferation of both smooth endoplasmic reticulum and mitochondrial population. Treatment with PB also gave rise to a general increase in peroxidative reactions (evaluated measuring malondialdehyde and hydroperoxides (HPs)), in the different cell compartments, even though HPs were not found significantly increased in mitochondrial fraction. The increase in peroxidative processes was associated with significant decreases in antioxidant concentration (expressed in terms of equivalent concentration of an antioxidant, such as the desferrioxamine), in all preparations from PB-treated rats. The response to oxidative stress in vitro (evaluated determining the parameters characterizing light emission from preparations stressed with sodium perborate) showed a substantial PB-induced increase in the susceptibility to oxidative challenge only in liver homogenate. The lack of changes in the mitochondrial preparations is likely due to decrease in concentration of both free radical producing species and antioxidants. The lack of changes in microsomal fraction is apparently in contrast with its lower oxidant capacity and higher content of cytochromes which are able to determine sensitivity to pro-oxidants. However, it could be due to the ability of cytochrome P450 to interact with the active oxygen species formed at its active center.
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PMID:Effect of phenobarbital treatment on characteristics determining susceptibility to oxidants of homogenates, mitochondria and microsomes from rat liver. 994 58


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