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

---

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

Unlike halogenated benzenes, trichlorophenols did not induce xenobiotic metabolism in the rat. 2,3,5-, 2,3,6-, 2,4,5-, and 2,4,6-Trichlorophenol at doses as high as 400 mg/kg p.o. daily for 14 days did not alter EPN detoxification. Only 2,4,5-trichlorophenol at the highest dose decreased microsomal NADPH-cytochrome c reductase activity and cytochrome P-450 content. In vitro, all 4 isomers inhibited EPN detoxification and the demethylation of p-nitroanisole. UDP-glucuronyltransferase was not altered in vivo and was only slightly inhibited in vitro by 2,3,5- and 2,4,5-trichlorophenol. The compounds were not hepatotoxic as assessed by measurement of hepatic glucose-6-phosphatase and serum sorbitol dehydrogenase.
...
PMID:Effect of trichlorophenols on xenobiotic metabolism in the rat. 10 51

Once a child is born its survival depends on the maturation of the blood glucose homeostatic control mechanisms. When this fails or where there is an inborn error of metabolism the infant is susceptible to potentially fatal hypoglycaemic episodes. A variety of environmental stresses, either singly or in combination, such as inappropriate or low caloric intake, acute infections of childhood, endotoxaemia, fever, xenobiotic exposure, oxidative stress or anaphylaxis, can greatly exacerbate the deficiency of the normal homeostatic compensatory mechanism and result in the onset of hypoglycaemia. Various inborn errors have been found in infants who died of SIDS. Our approach to this problem has been to use the six microsomal glucose-6-phosphatase proteins as a model system to study defects in carbohydrate metabolism in cases of SIDS. Initial studies determined the ontogeny of the glucose-6-phosphatase proteins and showed that intact microsomes isolated from unfrozen liver samples can be used to study glucose-6-phosphatase in cases of SIDS that were presumably due to the low concentrations of liver lipid peroxidation. More recently we have used a combination of techniques to demonstrate the abnormalities of glucose-6-phosphatase in cases of SIDS. Classic gross pathology and histology have now clearly defined the various subgroups of sudden and unexpected deaths of infancy. This now enables us to develop new molecular approaches to predict and prevent hypoglycaemia in infants who are at risk of SIDS.
...
PMID:Glucose metabolism and hypoglycaemia in SIDS. 133 59

The modifying action of chronic liver injury on the process of hepatocarcinogenesis was investigated. To induce cirrhosis or fibrosis F344 rats received CCl4 alone or in combination with phenobarbital, either before (model 1) or after (model 2) the application of initiator, diethylnitrosamine (DENA). In these models, morphology, tumor incidence as well as polysubstrate monooxygenase system, gamma-glutamyltransferase (GGT) and glucose-6-phosphatase (G-6-Pase) were studied. The data presented show that in model 1 the tumor incidence was much lower than in rats treated with DENA alone. This reduction appeared to be associated with the decrease in cytochrome P450 content occurring in model 1 after DENA administration. Promotion of the hepatocarcinogenic process was observed when CCl4 injury followed the application of DENA (model 2). Comparison of marker enzymes in cirrhotic livers and in tumors either with or without cirrhosis indicated that changes in cytochrome P450 and G-6-Pase were rather the results of parenchymal damage, while GGT was elevated only in tumorous livers. In tumorous livers none of the xenobiotic metabolizing activities decreased as much as the cytochrome P450 content of the same samples. Thus conceivably the cytochrome P450 operates more rapidly in tumors than in normal livers.
...
PMID:Modification of DENA-induced hepatocarcinogenesis by CCl4 cirrhosis. Comparison of the marker enzyme patterns. 135 Feb 34

Rats were treated with doxorubicin (2.5 mg/kg body wt, iv) once a week for 8 weeks. Alpha-Tocopherol (400 mg/kg body wt/day) was co-administered orally for 2 months. Cytochrome-P450 (Cyt-P450) and Cytochrome-b5 (Cyt-b5) levels decreased significantly in doxorubicin treated rats. Significant decreases were observed in glucose-6-phosphatase, Cyt-P450 and Cyt-b5 reductase activities. In vitro lipid peroxidation study showed that alpha-tocopherol significantly minimises the lipid peroxide formation by doxorubicin. There was a significant change in microsomal cholesterol and phospholipid levels. Alpha-Tocopherol co-administration reduced the alterations in xenobiotic metabolising system and microsomal lipid levels. The results were discussed with reference to drug metabolising enzymes, lipid peroxidation and antioxidant nature of alpha-tocopherol.
...
PMID:Effect of alpha-tocopherol on doxorubicin-induced changes in rat liver and heart microsomes. 176 24

Formation of the N-(deoxyguanosin-8-yl)-aminofluorene adduct was studied in enzyme-altered foci induced by four different liver carcinogenesis models. Foci were detected and scored for enzyme phenotype by a computer-aided image overlay technique. Localization of the enzymes gamma-glutamyl transpeptidase, canalicular ATPase and glucose-6-phosphatase was performed by enzyme histochemistry, allowing identification of foci of seven different phenotypes. Patterns of foci obtained by image overlay were compared to in situ 2-acetylaminofluorene--DNA adduct distribution obtained by immunofluorescence. Foci were induced by the following models: (1) chronic feeding of 0.02% 2-acetylaminofluorene (2-AAF) for 8 weeks; (2) intubation of diethylnitrosamine (DEN) (10 mg/kg) 24 h after a 70% partial hepatectomy (PH), followed 8 weeks later by a diet containing 0.05% phenobarbital for 9 months; (3) intubation of DEN (10 mg/kg) 24 h after PH, followed by a diet containing 0.01% ciprofibrate for 5 months, and after an additional 4 months a diet containing 0.05% phenobarbital for 2 months; (4) maintenance for 7.5, 16.5 or 19.5 months after transplantation of DEN/2-AAF/PH ('Solt-Farber' protocol) donor liver cells into host rats receiving a brief 2-AAF/PH selective regimen then no further treatment until sacrifice. To test the capacity of both foci and morphologically normal livers to form DNA adducts, the animals in models 2-4 received a diet containing 0.02% 2-AAF for 5 or 6 days before sacrifice. In all of the enzyme-altered foci identified in models 1-3 there were no DNA adducts visible by immunofluorescence. Scattered groups of positive cells were occasionally seen in the otherwise dark foci induced by model 4. For technical reasons some enzyme-altered foci were not identifiable on the fluorescence-stained slides. In liver serial sections from rats in models 1-4, there were 75, 304, 125 and 68 enzyme-altered foci of seven different phenotypes which were identified as AF-DNA negative. In models 1 and 4 there were some additional adduct-negative foci not associated with any of the seven identified focus phenotypes. These studies demonstrate that loss of the ability to form DNA adducts in hepatic enzyme-altered foci is a common and very early biochemical adaptation to xenobiotic exposure in different hepatocarcinogenesis models. This adaptation also is retained by the majority of foci in later stages of hepatocarcinogenesis.
...
PMID:Lack of acetylaminofluorene--DNA adduct formation in enzyme-altered foci of rat liver. 289 93

Adult (male, 75-90 days old) and immature rats (both sexes, 11-12 days old) were treated with allyl alcohol or bromobenzene to induce periportal or centrilobular hepatic injury, respectively. Histologically confirmed liver lesions were produced in adult rats with both treatments. In adult rats, allyl alcohol decreased hepatic cytochrome P-450, benzphetamine N-demethylation, and ethoxyresorufin O-deethylation activities all by about 30%, whereas bromobenzene influenced these parameters differently: cytochrome P-450 was lowered by 55%, benzphetamine N-demethylation by 80%, and ethoxyresorufin O-deethylation by 90%. Cytochrome c reductase, 5'-nucleotidase, glucose-6-phosphatase, and glutamate-pyruvate transaminase activities were not significantly influenced. In immature rats, allyl alcohol did not produce histopathological alterations in liver, but did lower both cytochrome P-450 concentration (30%) and ethoxyresorufin O-deethylation (75%). Benzphetamine N-demethylation was not significantly affected. Bromobenzene produced typical centrilobular liver damage and a decrease of both cytochrome P-450 (20%) and ethoxyresorufin O-deethylation (50%). Benzphetamine N-demethylation was increased slightly, but not significantly. The differences in effects of the two hepatotoxins in adult vs immature rats seem to indicate that the hepatocellular heterogeneity of xenobiotic metabolism which is seen in adult liver (perivenous vs periportal areas) is not well developed in the immature animal.
...
PMID:Functional hepatocellular heterogeneity determined by the hepatotoxins allyl alcohol and bromobenzene in immature and adult Fischer 344 rats. 300 82

Dietary restriction extends maximum life span in rodents by unknown mechanisms. We compared livers from 12- and 24-mo-old mice fed control (C, approximately 95 kcal/wk) or restricted (R, approximately 55 kcal/wk) amounts of diet since 3 wk of age. We hypothesized that dietary restriction might alter the activity levels of enzymes with possible relevance to aging processes. The enzymes included several xenobiotic metabolizers, radical scavengers (catalase, superoxide dismutase, glutathione peroxidase), superoxide sources (xanthine oxidase, peroxisomal beta-oxidation of palmitoyl-CoA) and glucose-6-phosphatase. Lipid peroxidation (LP) was also measured. Comparing 12- and 24-mo-old mice, the strongest diet or age effect was an increased catalase activity for group R (42% higher at 12 mo, 64% at 24 mo). LP was clearly lower in group R at 12 mo (a 30% decrease) and somewhat lower (13%) at 24 mo than in group C. Similarly, in 12-mo-old C and R mice injected with either the P-450 inducer beta-naphthoflavone (beta-NF in corn oil) or with corn oil alone. R mice showed higher catalase activity (40-44%) and lower LP (43-46%) in both beta-NF-injected and vehicle-injected groups. These data suggest that if free radical damage is involved in aging, it may be a particular kind of damage, that is, that in part prevented by a selective increase in catalase activity.
...
PMID:Influences of dietary restriction and age on liver enzyme activities and lipid peroxidation in mice. 303 Dec 54

Previous studies have demonstrated that the hepatotoxin carbon tetrachloride rapidly promotes lipid peroxidation and inhibits microsomal calcium sequestration, microsomal glucose-6-phosphatase activity and cytochrome P-450. Due to its profound effects on lipid peroxidation, we have examined the oral administration of 2.5 ml/kg carbon tetrachloride on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. Urine samples were collected up to 48 h after treatment. The urinary metabolites were identified and quantitated by gas chromatography-mass spectrometry and high-pressure liquid chromatography. Time-dependent increases in the urinary excretion of the four metabolites were observed after carbon tetrachloride administration. At 48 h after treatment, the increases in the excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approximately 55, 78, 57 and 268%, respectively, relative to control values. The data were expressed in nanomoles per kilogram body weight per 4.5 h. The results clearly demonstrate that carbon tetrachloride increases the urinary excretion of four lipid metabolites which may serve as noninvasive biomarkers of xenobiotic-induced lipid peroxidation.
...
PMID:Carbon-tetrachloride-induced urinary excretion of formaldehyde, malondialdehyde, acetaldehyde and acetone in rats. 841 71

Our earlier studies in vitro have shown that eugenol inhibits liver microsomal monooxygenase activities and carbon tetrachloride (CCl4)-induced lipid peroxidation (Free Rad. Res. 20, 253-266, 1994). The objective of the present investigation was to study the in vivo protective effect of eugenol against CCl4 toxicity. Eugenol (5 or 25 mg/kg body wt) given orally for 3 consecutive days did not alter the levels of serum glutamic oxalacetic transaminase (SGOT), microsomal enzymes such as cytochrome P450 reductase, glucose-6-phosphatase (G-6-Pase) xenobiotic-metabolizing enzymes (aminopyrine-N-demethylase, N-nitrosodimethylamine-demethylase and ethoxyresorufin-O-deethylase) and liver histology. Doses of eugenol (5 or 25 mg/kg) administered intragastrically to each rat on three consecutive days i.e. 48 hr, 24 hr and 30 min before a single oral dose of CCl4 (2.5 ml/kg body wt) prevented the rise in SGOT level without appreciable improvement in morphological changes in liver. Eugenol pretreatment also did not influence the decrease in microsomal cytochrome P450 content, G-6-Pase and xenobiotic-metabolizing enzymes brought about by CCl4. Since eugenol is metabolized and cleared rapidly from the body, the dose schedule was modified in another experiment. Eugenol (0.2, 1.0, 5.0 or 25 mg/kg) when given thrice orally i.e. prior to (-1 hr) along with (0 hr) and after (+3 hr) the i.p. administration of CCl4 (0.4 ml/kg) prevented significantly the rise in SGOT activity as well as liver necrosis. The protective effect was more evident at 1 mg and 5 mg eugenol doses. However, the decrease in microsomal G-6-Pase activity by CCl4 treatment was not prevented by eugenol suggesting that the damage to endoplasmic reticulum is not protected. The protective effect of eugenol against CCl4 induced hepatotoxicity is more evident when it is given concurrently or soon after rather than much before CCl4 treatment.
...
PMID:The protective effects of eugenol on carbon tetrachloride induced hepatotoxicity in rats. 857 54

The use of in vitro systems in the assessment of xenobiotic metabolism has distinct advantages and disadvantages. While isolated hepatocytes and microsomes prepared from human liver may be used to generate data for comparisons among species and in vitro systems, such comparisons are generally performed on the basis of microsomal protein or million (viable) hepatocytes. Recently, in vitro data have been investigated for their value as quantitative predictors of in vivo metabolic capacity. Because of the existence of large amounts of trichloroethylene (TRI) data in the human, we have examined the metabolism of TRI as a case study in the development of a method to compare metabolism across species using in vitro systems and for extrapolation of metabolic rates from in vitro to in vivo. TRI is well metabolized by human hepatocytes in culture with a K(m) of 266 +/- 202 ppm (mean +/- SD) in headspace and a Vmax of 16.1 +/- 12.9 nmol/h/10(6) viable hepatocytes. We determined that human liver contains approximately 116 x 10(6) hepatocytes and 20.8 mg microsomal protein/g, based on DNA recovery and glucose-6-phosphatase activity, respectively. Thus, the microsomal protein content of hepatocytes is 179 micrograms microsomal protein/10(6) isolated hepatocytes. The microsomal apparent Vmax value of 1589 pmol/min/mg microsomal protein extrapolates to 17.07 nmol/h/10(6) hepatocytes. The combination of protein recovery and metabolic rate predicted a Vmax of approximately 1400 nmol/h/g human liver, which, when extrapolated and incorporated into an existing physiologically based pharmacokinetic (PBPK) model for TRI, slightly underpredicted TRI metabolism in the intact human. The quantitation, extrapolation, and inclusion of extrahepatic and cytochrome P450 (CYP)-independent TRI metabolism may increase the predictive value of this approach.
...
PMID:In vitro to in vivo extrapolation for trichloroethylene metabolism in humans. 985 6


1 2 Next >>

---