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 activities of pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and glycogen synthetase (GS) were determined in the cancerous and in the apparently uninvolved (host) regions of livers from primary hepatoma patients as well as in normal adult human livers and human fetal livers. The activities of these enzymes were also assayed in a fairly fast-growing, 3'-methyl-4-dimethylaminoazobenzene-induced transplantable rat hepatoma and in hepatoma cell lines derived from both rat and human tumors. In the human hepatoma, as in the rat hepatoma, the activities of PC, PEPCK, and G6Pase were considerably reduced, compared to those in the host liver. The activities of both the a (glucose 6-phosphate-independent) and b (glucose 6-phosphate-dependent) forms of GS were also lower in human and rat hepatomas than in the respective host livers. Activities of PC, PEPCK, and G6Pase in the human hepatomas were often comparable with those of fetal livers. In rat and human hepatoma cells, the activities of PC, PEPCK, and G6Pase were similar to or lower than the activities in the respective hepatomas; the activities of GS a were also similar to those in the hepatoma, whereas the activities of GS b were somewhat higher.
Cancer Res 1978 May
PMID:Activities of key gluconeogenic enzymes and glycogen synthase in rat and human livers, hepatomas, and hepatoma cell cultures. 20 62

Three gluconeogenic enzymes, P-pyruvate carboxykinase (PPCK), fructose-1-6 bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) were measured in identified structures of rat nephron from 2 days before birth to maturity. In the proximal convoluted tubule, the three enzymes increased from the earliest age assayed to +14 days (PPCK, 7-fold, FBPase, 2-fold and G6Pase, 50-fold). Among the 7 defined structures that were analyzed, highest levels at all ages were in the proximal convoluted tubule with almost no activity in the distal convoluted tubule. All three enzymes had negligible activity in the neogenic zone and mesenchyme. Supported by grants from the Public Health Service (HD 03891 and NS-05221) and the American Cancer Society (P-78).
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PMID:Gluconeogenic enzymes in defined structures of developing rat nephron. 21 Sep 97

The effect of chronic ethanol consumption on the ability of isolated liver fractions to metabolize the carcinogen N-nitrosopyrrolidine (NPY) was examined. Microsomal fractions of treated animals exhibited increased rates of alpha-hydroxylation of NPY. Similar increases in the specific activities of aniline hydroxylase, reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase, and the specific content of cytochrome P-450 were also observed. In contrast, no differences in the specific activities of benzo(a)pyrene hydroxylase or glucose-6-phosphatase were observed. Liver postmitochondrial supernatants from ethanol-consuming animals were able to produce 5 times more mutants than did control preparations. It is concluded that alpha-hydroxylation of NPY is probably the mechanism by which NPY is converted to a mutagen and that this pathway can be induced by ethanol.
Cancer Res 1979 Mar
PMID:Enhanced metabolism and mutagenesis of nitrosopyrrolidine in liver fractions isolated from chronic ethanol-consuming hamsters. 57 Aug 82

In previous studies, artificial sunlight and riboflavin synergistically increased acute aflatoxin toxicity in rats. Three new experiments were designed to provide information on the interaction of riboflavin, aflatoxin, and light. In a study of carcinogenesis, rats received low levels of aflatoxin 5 days/wk for 3 wk; 30 min after each dosing, half of them were irradiated for 2 hr. In some, levels of glucose-6-phosphatase and acid phosphatase were determined 5 days after completion of treatment. Remaining rats were killed at 30 or 53 wk. All underwent complete necropsies and histopathologic examination. In the second experiment, rats were dosed with riboflavin and divided into four groups: no further treatment; aflatoxin (LD50); irradiation (1-2 hr); or aflatoxin plus irradiation. Blood riboflavin levels were determined at intervals following these treatments. In the third experiment, the chemical reactions of irradated aflatoxin and/or riboflavin were studied by uv spectroscopy and TLC. The 53-wk study showed clearly that light decreased the incidence of aflatoxin-induced cancer. The other results may provide an explanation. Aflatoxin caused blood riboflavin levels to decrease-an effect enhanced by irradiation, suggesting that photosensitized riboflavin and aflatoxin form a complex. This interpretation gains support from studies in vitro that showed that riboflavin quenched aflatoxin photodegradation, perhaps by complexing with aflatoxin. Thus, low, carcinogenic doses of aflatoxin may complex with endogenous, photosensitized riboflavin, inhibiting its degradation into carcinogenic metabolites.
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PMID:Some interactions of light, riboflavin, and aflatoxin B1 in vivo and in vitro. 124 82

Cytochemical and electron microscopic investigations of neoplastic nodules induced in the rat liver by nitrosomorpholine or thioacetamide show that most neoplastic nodules are comprised of a rather heterogeneous cell population. At least four different types of altered hepatocytes can be distinguished: (a) "clear" glycogen storage cells with a dislocation and relative reduction of the granular endoplasmic reticulum; (b) "acidophilic" glycogen storage cells with a hypertrophy of the agranular endoplasmic reticulum; (c) fat-storing cells; and (d) basophilic cells poor in glycogen and rich in ribosomes. In addition, there are diverse intermediate cell types. The cytochemically demonstrable activity of glucose-6-phosphatase is reduced in most neoplastic nodules, but it may also be normal or even increased. The clear and the acidophilic cells precede the development of the neoplastic nodules by weeks and months. They usually form foci which are taken to be preneoplastic lesions. During the formation of neoplastic nodules and hepatocellular carcinomas originating for such foci the glycogen of the clear and the acidophilic cells is progressively reduced, whereas the number of ribosomes (basophilia) increases. This process, which may be accompanied by a transitory accumulation of fat, leads to the evolution of basophilic carcinoma cells. We conclude from these observations that the majority of the neoplastic nodules consist of a mixture of precancerous, definitely cancerous, and diverse intermediate cells. Neoplastic nodules in which basophilic cells prevail may already be carcinomas. Although the neoplastic nodules seem to be a frequent precursor of hepatocellular carcinomas, the latter may also develop without going through the nodule stage.
Cancer Res 1976 Jul
PMID:Cytology and cytogenesis of neoplastic (hyperplastic) hepatic nodules. 127 65

We studied the development of liver tumors in male transforming growth factor alpha (TGF-alpha) transgenic mice of the CD1 strain and examined the expression of the transgene by immunohistochemistry and in situ hybridization. Livers of 4-5-week-old transgenic mice contained areas of centribobular hypertrophy with low glucose-6-phosphatase activity. These areas progressively expanded, and hypertrophy and dysplasia became generalized in livers of mice at 10-12 months of age. The expression of the transgene, determined by either immunohistochemistry or in situ hybridization, was uneven in animals that were 10 weeks old or older. The positive hepatocytes formed patches with a predominant centrilobular distribution. We studied a total of 23 liver tumors (7 hepatocellular carcinomas and 16 adenomas) obtained from 11 mice at 13-15 months of age and from one 7-month-old animal which received zinc sulfate to induce the transgene. The carcinomas were well differentiated tumors, without glucose-6-phosphatase or gamma-glutamyltranspeptidase activity, that developed from the dysplastic parenchyma and occasionally within an adenoma. In all carcinomas and in 56% of the adenomas there was overexpression of the transgene in relationship to the surrounding tissue. The majority of the tumors that overexpressed TGF-alpha were alpha-fetoprotein positive, while alpha-fetoprotein staining was not detected in tumors (all adenomas) that did not show excessive transgene expression. We conclude that TGF-alpha functions as a promoter of liver carcinogenesis through its effect as an autocrine inducer of hepatocyte proliferation. Further, the data indicate that TGF-alpha overexpression may favor tumor progression.
Cancer Res 1992 Oct 01
PMID:Development of liver tumors in transforming growth factor alpha transgenic mice. 132 2

Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.
Jpn J Cancer Res 1992 Nov
PMID:Effects of modifying agents on conformity of enzyme phenotype and proliferative potential in focal preneoplastic and neoplastic liver cell lesions in rats. 133 90

Dehydroepiandrosterone (DHEA), a C19 adrenal steroid hormone, induces peroxisome proliferation in liver cells and is hepatocarcinogenic in the rat. The present study deals with the phenotypic properties of DHEA-induced liver lesions. A majority of the altered areas (80-87%), neoplastic nodules (> 94%) and hepatocellular carcinomas (HCC, 80-100%) lacked the marker enzymes gamma-glutamyltranspeptidase and placental form of glutathione S-transferase (GSTP). Northern blot analysis of HCC from 4 rats revealed no detectable GSTP mRNA. These HCC, however, showed a marked decrease in the staining of glucose-6-phosphatase and adenosine triphosphatase. These results indicate that the phenotypic properties of liver tumors induced by DHEA and amphipathic carboxylate peroxisome proliferators are similar.
Jpn J Cancer Res 1992 Nov
PMID:Phenotypic properties of liver tumors induced by dehydroepiandrosterone in F-344 rats. 133 91

Positron emission tomography (PET) fluorodeoxyglucose (FDG) studies are useful for identifying foci of increased FDG uptake in liver metastases, because of the high glycolytic rate of malignancies, as well as for monitoring changes in tumor glucose metabolism during treatment. We performed 15 kinetic PET FDG studies in four patients with metastatic liver disease. We produced parametric images of glucose metabolism in terms of the rate constant K (ml/min/g) for net phosphorylation of FDG. Tumor K values, estimated with nonlinear regression, correlated well with K values estimated with Patlak graphical analysis (r = 0.96), validating the assumption of low k4* values in liver metastases and supporting the use of pixel by pixel Patlak plot analysis of the data to generate parametric images. In normal liver, high levels of glucose-6-phosphatase produce much higher values of k4* than in liver metastases. Uncorrected Patlak graphical analysis underestimates K in normal liver, but this further increases the contrast between tumor and liver and facilitates both tumor detection and quantification. The technique is computationally feasible and is well suited for serial evaluations of tumor metabolism during treatment.
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PMID:Quantification of glucose utilization in liver metastases: parametric imaging of FDG uptake with PET. 152 57

Tumor uptake of 18F-fluorodeoxyglucose (FDG) was studied by dynamic positron emission tomography (PET) in 23 cases of hepatocellular carcinoma. The metabolic rate constants, K1 to K4, were generated by non-linear least square fitting method. We confirmed that K3 from the PET study significantly correlated with directly measured hexokinase activity of the cancer tissue. The region of HCC always had higher K3 values, which represents the hexokinase activity compared with the non-cancerous region. By FDG images, however, in 50% of cases the cancer region could not be clearly defined from the surrounding noncancerous hepatic tissue. These HCC cases without accumulation of FDG had a high ratio of K4/K3 (K4 represents glucose-6-phosphatase activity), which correlated well with the inverse ratio of FDG accumulating images on PET. According to the PET images which is represented by K4/K3 and the hexokinase activity which is represented by K3, we divided these 23 cases into three groups and retrospectively compared their survival rates. The groups with high K4/K3 (greater than or equal to 0.40) had longer survival than other groups. From the view point of glucose metabolism, the value of K4/K3 calculated from dynamic studies of FDG-PET may represent the functional differentiation of HCC.
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PMID:[Can fluorodeoxyglucose-positron emission tomography evaluate the functional differentiation of hepatocellular carcinoma]. 166 76


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