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)

Administration of thiobenzamide in a single dose (25 mg/100 g body wt by stomach tube) to male rats induced centrilobular necrosis, which became evident 10 h after the poisoning. In the meantime liver weight and water content underwent changes, glycogen was lost, triglycerides accumulated in the liver while decreasing in serum, [3H] leucine uptake in proteins was impaired and the activity of glucose-6-phosphatase and aminopyrine demethylase decreased. The activity of NADPH-cytochrome c reductase remained unchanged, whereas a reduction of the microsomal cytochrome P-450 occurred. The liver amount of reduced glutathione underwent no significant changes. Pretreatment of the animals with cobalt chloride or 20-methylcholanthrene decreased the liver damage caused by the drug. The in vitro addition of thiobenzamide to liver microsomes resulted in a spectral change. The appearance of conjugated dienes among microsomal lipids from drug-treated rats indicated for a lipoperoxidation taking place in vivo.
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PMID:Early biochemical liver changes following thiobenzamide poisoning. 51 72

We describe an automated, homogeneous, glucose oxidase-coupled method for the determination of glucose-6-phosphatase activity in tissue extracts. The method is based on measurement of the rate of glucose formation by the Trinder reaction, in which the end product is a quinoneimine dye which absorbs maximally at 505 nm and has a molar extinction coefficient of 5700. The incubation mixture contains 20 microL of tissue extract, 25 microL of 0.5 M phosphate buffer, pH 7.0, 175 microL of Trinder/glucose-6-phosphate reagent, and 30 microL of distilled water. After a delay period of 15 min, to exhaust any glucose endogenously present in the extract, glucose production from glucose-6-phosphate is monitored at 505 nm for 5 min in a centrifugal analyzer. The Km was 13 mM over a 10-fold range in glucose-6-phosphate concentration and the reaction was linear up to about 250 U/L. Within-run CV of the assay at activities of 48 and 190 U/L ranged between 2.5-5.0%. The between-run CV at 190 U/L was 5.1%.
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PMID:Homogeneous trinder-coupled assay for the determination of glucose-6-phosphatase activity in tissue extracts. 132 Apr 68

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.
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PMID:Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. 133 43

The ethanol precipitate fraction (RG-WP) obtained from the hot water extract from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao is mainly composed of pectin-like polysaccharide, and exhibited hypoglycemic activity in normal and streptozotocin-induced mice by intraperitoneal administration of the fraction. The results obtained after chemical modification and proteinase treatments of RG-WP suggest that the activity exists in the polysaccharide moiety. Furthermore, the effect of RG-WP on the activities of enzymes responsible for the glucose metabolism in the liver of normal mouse was studied to elucidate the mechanism of the hypoglycemic activity. Administration of RG-WP to normal mice significantly increased the activities of hepatic glucokinase and glucose-6-phosphatase dehydrogenase, but decreased those of hepatic glucose-6-phosphatase and phosphofructokinase. RG-WP stimulated the secretion of insulin and reduced the glycogen content in the liver of normal mouse.
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PMID:[Hypoglycemic activity of polysaccharide fraction from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao and the effect on carbohydrate metabolism in normal mouse liver]. 143 91

Renal clear cell tubules and clear/acidophilic cell tumors were induced in male Sprague-Dawley rats by 7 weeks oral administration (stop model) of N-nitrosomorpholine (NNM) at a concentration of 12 mg/100 ml in the drinking water. Twelve, 23 and 34 weeks after withdrawal of NNM serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glucose transporter proteins (GLUT1, GLUT2), glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyltransferase (GGT). Clear cell (glycogenotic) tubules first appeared at 23 weeks, and clear/acidophilic cell tumors at 34 weeks after withdrawal of the carcinogen. G6Pase, ALP, GGT and GLUT2 were absent in clear cell tubules, clear/acidophilic cell tubules, and clear/acidophilic cell tumors indicating a sequential origin of all these types of lesions from the collecting duct system, in line with previous morphological findings. In comparison to the collecting duct epithelium, glycogenotic tubules demonstrated an increased activity of PHO and reduced activities of glycolytic and mitochondrial enzymes, which were accompanied by a strongly reduced expression of GLUT1. Moderately increased activities of glycolytic and mitochondrial enzymes were observed in the clear cells of clear/acidophilic cell tubules and tumors compared with those in glycogenotic tubules. They had slightly increased activities of the glycolytic enzymes GAPDH and PK compared with normal collecting duct epithelium, while most of them were nearly lacking in GLUT1. Our findings suggest that glycogen storage is not due to an increased uptake of glucose from the blood, but results from a disturbance in intracellular flux of metabolites. The development of clear cell tubules from the normal collecting duct epithelium is accompanied by a markedly decreased expression of GLUT1 along with a reduction in glycolytic and mitochondrial enzymes. This reduction of enzyme activities is replaced by an increase in enzyme activities in clear/acidophilic cell tumors indicating a fundamental shift in carbohydrate metabolism during progression from preneoplastic to neoplastic lesions.
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PMID:Sequential changes in glycogen content, expression of glucose transporters and enzymic patterns during development of clear/acidophilic cell tumors in rat kidney. 147 41

Primary cultures of renal rabbit proximal tubule cells were initiated from a pure suspension of proximal tubule fragments. Proximal tubule cells were grown in a hormone-supplemented, serum-free medium containing low concentrations of antibiotics. Confluent monolayers exhibited multicellular dome formation, indicating the presence of transepithelial solute and water transport. Ultrastructural examination revealed a monolayer of polarized epithelial cells with tight junctions and sparse membraneous microvilli facing the culture medium. Time course biochemical characterization was performed using a palette of 12 enzymes, representative of important metabolic functions or pathways. Brush-border-associated enzymes (gamma-glutamyl transpeptidase and alanine aminopeptidase) were moderately reduced throughout the culture whereas alkaline phosphatase was markedly decreased at confluency. Mitochondrial and lysosomal marker enzymes were well preserved over the culture period. Glutathione-S-transferase activity remained stable during the 16-day culture period investigated. Glycolysis enzyme activities (lactate dehydrogenase and hexokinase) were enhanced, as a function of culture age. Na(+)-K(+)-ATPase activity rise was concomitant with the increase of glycolysis marker enzymes. In contrast, the gluconeogenesis marker enzyme, glucose-6-phosphatase, fell dramatically to reach a low level equivalent to 4% of the activity measured in isolated proximal tubules. Primary cultures exhibited several differentiated functions of the proximal tubule cell: (a) PTH alone was able to induce a significant stimulation of adenylate cyclase activity, unlike isoproterenol, thyrocalcitonin, and arginine vasopressin, and (b) sodium-dependent alpha-methylglucoside (AMG) transport was detected. This AMG uptake was selectively inhibited by phlorizin (5 X 10(-3) M), which is a competitive inhibitor of glucose uptake at the apical membrane. Complete characterization made it possible to investigate hitherto unexplored aspects of in vitro cultured proximal tubule cells. This primary culture model could provide a useful and reliable tool to investigate in vitro renal proximal tubule function, under normal conditions or after a drug-induced toxicity.
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PMID:Biochemical, functional, and morphological characterization of a primary culture of rabbit proximal tubule cells. 167

In Wistar rats poisoned by daily addition of sodium nitrite to drinking water (1 g/dm3), determination was made of the dynamics of changes in: blood methemoglobin and 2,3-diphosphoglyceric acid levels, contents of protein and non-protein thiol groups in erythrocytes, blood glucose-6-phosphate dehydrogenase and peroxide dismutase activities, as well as plasma vitamin E and hydroxyproline levels, Determinations were performed after 15, 30, 45, 60, 75 and 90 days of poisoning. There occurred a linear relationship between the drop in glucose-6-phosphatase dehydrogenase activity and in vitamin E level, on one hand, and the duration of poisoning with sodium nitrite. Moreover, a significant rise of 2,3-diphosphoglyceric acid level in erythrocytes and a decrease in the non-protein thiol groups took place. Rhe results indicated that the determinations--in blood--of: methemoglobin, glucose-6-phosphate dehydrogenase activity in erythrocytes, and vitamin E in plasma or serum, could be included among the diagnostic tests performed (at the laboratories attached to industrial plants or making part of the industrial health service) for evaluation of the health hazard in the nitro-compound industry or in other nitrite contaminated working places.
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PMID:[Examination of dynamic changes of certain biochemical parameters in blood of rats poisoned with sodium nitrite]. 184 17

Dichloroacetic acid (DCA) has recently been shown to increase significantly the incidence of hepatic adenomas (HAs) and hepatocarcinomas (HCs) in male B6C3F1 mice. Although little is known about the mechanism of DCA carcinogenesis, chronic ingestion of the compound in drinking water induces primarily hyperplastic nodules (HNs) prior to the appearance of HAs and HCs. Given the putative preneoplastic potential of the HNs, we undertook this study to determine the role of the HNs in the progression of DCA-induced hepatocarcinogenesis. This role was assessed by detecting the expression of five different tumor markers: p21 ras, p39 c-jun, phosphotyrosine, tumor-associated aldehyde dehydrogenase and alpha-fetoprotein, all known from previous studies to be expressed more often in neoplastic liver lesions than in normal liver. Tumor marker expression was detected by immunohistochemical methods using formalin-fixed, paraffin-embedded sections of normal B6C3F1 mouse liver, and DCA-induced HNs, HAs and HCs. The results demonstrated that, except for the c-jun marker, HNs expressed the markers significantly less often than either HAs or HCs. Equal expression of c-jun occurred in any of the three lesion types. Although these results could be used to argue that no relationship existed between HNs and later-appearing HAs and HCs, those HNs that were marker positive contained small nests of marker-positive hepatocytes among a field of normally appearing unstained hepatocytes. No similar nests of marker-positive cells were detected in any area of normal liver outside the HNs. Also very few altered hepatic foci (AF) were detected with these markers or with hematoxylin and eosin, or with histochemical stains for ATPase or glucose-6-phosphatase deficiencies. These results suggested that these nests within some HNs were areas of transformed, or neoplastic hepatocytes. Phenotypic heterogeneity analysis, in which the number of tumor markers co-expressed by any given lesion was examined, confirmed a significantly greater percentage of HAs and HCs expressing multiple markers than HNs. Those HNs that expressed multiple markers, however, expressed at the same frequency as HAs and HCs and the expression was confined to the same nests of cells. Taken together, these data suggest that these nests of marker-positive cells within the HNs were neoplastic and could develop into later-appearing HAs and/or HCs. The absence of marker expression in normal liver and limited expression in the few AF indicates that the HNs may be the only significant preneoplastic lesion in DCA-induced hepatocarcinogenesis.
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PMID:The role of hyperplastic nodules in dichloroacetic acid-induced hepatocarcinogenesis in B6C3F1 male mice. 186 Jan 58

Although carbon tetrachloride (CCl4) is of concern as a drinking water contaminant, it has been necessary in most oral toxicity studies to give CCl4 in an oil vehicle due to its limited water solubility. The primary objective of our study was to assess the influence of dosing vehicles on the acute hepatotoxicity of CCl4. Fasted 200- to 230-g rats were generally found to be more susceptible to CCl4 hepatotoxicity than fasted 300- to 330-g rats. A time-course study revealed that corn oil did not delay the onset or time of maximal liver injury by an oral 100 mg/kg dose of CCl4, but did reduce the extent of injury relative to that when the chemical was given undiluted or as an aqueous emulsion. Fasted 200- to 230-g male Sprague-Dawley rats were given 0, 10, 25, 50, 100, 250, 500, or 1000 mg CCl4/kg body wt by gavage: in corn oil; as an aqueous emulsion; as the undiluted chemical; and in the 10 and 25 mg/kg doses only, in water. Blood and liver samples were taken 24 hr after dosing for measurement of serum and microsomal enzymes. Pathological examination of liver samples was also conducted. Dose-dependent increases in serum enzyme levels and pathological changes and dose-dependent decreases in microsomal P450 and glucose-6-phosphatase activity were observed in each vehicle group. Both the 10 and 25 mg/kg oral doses of CCl4 in water caused significant elevations in serum enzymes and hepatic centrolobular vacuolation. The study revealed that acute hepatotoxicity was less pronounced at each dosage level in rats given CCl4 in corn oil than in other vehicle groups. These findings demonstrate that dosing vehicles can significantly influence the acute hepatotoxicity of CCl4 in rats and are a cause for additional consideration and review of the practice of routinely using vegetable oils as a diluent in studies of volatile organic compound (VOC) toxicity. The use of aqueous Emulphor emulsions appears more appropriate in acute toxicity studies of VOC drinking water contaminants such as CCl4, in that the emulsion did not substantially alter the toxicity of CCl4 from that of undiluted CCl4 or CCl4 ingested in water.
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PMID:Effect of oral dosing vehicles on the acute hepatotoxicity of carbon tetrachloride in rats. 229 70

Liver carcinogenesis was induced in rats by aflatoxin B1 (AFB1) enhanced by a choline-deficient diet. In Experiment 1, the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), was administered by gavage to one group only during AFB1 administration; another group received DFMO during AFB1 administration and for 2 months after carcinogen administration. These two groups were compared to two control groups, one given AFB1 and fed the choline-deficient diet and another fed the deficient diet only. In a second experiment, DFMO was administered at a concentration of 2% in the water for 3 weeks and then at 1% for the remainder of the study. Rats from each group in Experiment 1 were killed at 2, 8, and 10 months after AFB1 administration and the development of tumors was followed by histology; autoradiography of [3H]thymidine incorporation into DNA; enzyme histochemistry; and alpha-fetoprotein determination. The group given DFMO during AFB1 administration was not significantly different from the AFB1-treated control group at 2 and 8 months after AFB1 administration. However, at 10 months following AFB1 and DFMO administration, the [3H]thymidine-labeling index and glucose-6-phosphatase staining were significantly increased. This group had three animals bearing hepatocellular carcinomas as compared to none in the controls. The group given DFMO for 2 months after AFB1 administration had a significantly depressed growth rate 2 months later, but this difference was not apparent after 8 months. After 10 months, there was a significantly increased [3H] thymidine-labeling index and increased volume fraction of gamma-glutamyltranspeptidase in the AFB1-DFMO-treated group as compared to the controls. DFMO appeared to inhibit growth under some conditions, but if administration was discontinued after AFB1 exposure, it appeared to enhance tumorigenesis. In Experiment 2, where a larger dose of AFB1 was used and DFMO was administered in the water from start to finish of the experiment, DFMO inhibited tumor induction and depressed the appearance of markers examined during carcinogenesis. These data indicate that the regimen used for DFMO administration can markedly affect tumor induction.
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PMID:Effects of the irreversible ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, aflatoxin B1, and choline deficiency on hepatocarcinogenesis. 241 77


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