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 liver microsomal enzymes were studied in preparations from unanesthetized rats and rats anesthetized for one hour with nitrous oxide, diethyl ether, halothane or chloroform. Most of the enzymes studied were cytochrome P-450-dependent oxygenases that hydroxylate endogenous substrates. The other microsomal enzymes, assayed for comparison, included the cytochrome P-450-dependent aminopyrine demethylase, glucose-6-phosphatase, a dehydrogenase, and NADPH-cytochrome P-450 reductase. No anesthetic was associated with a significant change in activity of any enzyme studied. In rats pretreated with phenobarbital no anesthetic except chloroform changed enzymic activity. All hydroxylations were inhibited markedly by chloroform, as were a microsomal dehydrogenation, hydrolysis of glucose-6-phosphate, and NADPH-cytochrome P-450 reductase activity. Administration of alpha-tocopherol did not prevent the inhibition associated with chloroform in phenobarbital-induced animals. It is concluded that cytochrome P-450-dependent hydroxylations involved in metabolic processes normally proceeding in the endoplasmic reticulum of the liver are not permanently affected by the anesthetics used in this study. The inhibitory effect of chloroform after pretreatment with phenobarbital is unspecific and affects a large number of different microsomal enzymes. Evidence that mechanisms other than lipid peroxidation may be responsible for the toxic effects of chloroform in the liver is presented.
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PMID:Inhalation anesthetics and cytochrome P-450-dependent reactions in rat liver microsomes. 16 17

Plasma membranes, microsomes, and mitochondria were isolated from mouse fibroblast (LM) suspension cells by modification of several established procedures. Choline analogues such as N,N'-dimethylethanolamine, N-monomethylethanolamine, or ethanolamine were incorporated in vivo into phospholipids of all three cell fractions studied, but to varying degrees depending on the type of analogue used. The in vivo incorporation of these bases into membrane phospholipids produced no significant effect on the activities of seven membrane-bound enzymes: (Na+, K+)-ATPase, 5'-nucleotidase (plasma membranes); TPNH-cytochrome c reductase, glucose-6-phosphatase, inosine diphosphatase (microsomes); and succinate cytochrome c reductase (mitochondria). The incorporation of base analogues into phospholipids was accompanied by several compensatory mechanisms. (a) The quantity of both phosphatidylcholine and phosphatidylethanolamine decreased up to 75% and 50% respectively in 3 days. (b) The molar ratio of desmosterol/phospholipid in the plasma membranes of LM cells grown in suspension culture in the presence of choline analogues decreased from 0.65 to 0.45. (c) The percentage of lysophosphatidylcholine increased over 2-fold in the phospholipid of all subcellular fractions studied. The quantity of lysophosphatidylcholine was directly proportional to the number of methyl groups on the nitrogen atom of the base analogue supplemented to the cells. This was a specific effect since the quantity of lysophosphatidylethanolamine, the other major lysophospholipid, remained unchanged. (d) The ratio of zwitterionic phospholipids to acidic phospholipids remained relatively constant in all isolated membrane fractions regardless of analogue supplementation. Neither increase in the degree of unsaturation nor shortening of fatty acid chain length was noted in response to analogue supplementation.
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PMID:Isolation and characterization of subcellular membranes with altered phospholipid composition from cultured fibroblasts. 95 75

Male C3H/He, B6C3F1 and C57BL/6J mice were given a single injection of diethylnitrosamine (20 micrograms/g body wt) on day 15 after birth and animals were killed 17-29 (C3H/He and B6C3F1) and 29-46 weeks (C57BL/6J) after treatment. Carcinogen-induced liver lesions were identified by a deficiency in the marker enzyme glucose-6-phosphatase and the enzymatic phenotypes of these lesions were studied by enzyme and immunohistochemical methods using serial liver sections stained for seven additional histochemical markers. In all three mouse strains, liver lesions were characterized by an increased basophilia and a decreased expression of UDP-glucuronosyl-transferase, microsomal epoxide hydrolase and NADPH-cytochrome P450 reductase, while the cytochrome P450 isoenzymes 1A2, 2C6 and 2E1 were virtually unexpressed. Quantitative analyses revealed that throughout all periods of investigation, on average greater than 70% of the glucose-6-phosphatase-deficient lesions occupying up to 99% of the total volumetric fraction expressed concomitant alterations in at least one of these additional marker stainings. Upon determination of the phenotypic complexity levels, between 70 and 90% of lesions were found to contain alterations in at least six of the markers analysed, while lesions with alterations in less than three markers were comparatively infrequent. In the light of previous observations in the rat liver system, the relative homogeneity of enzyme phenotypes and the apparent lack of time-dependent changes in enzyme expression suggest that the majority of lesions of all three mouse strains possess an increased neoplastic character already from the very early beginning of the carcinogenic process in liver.
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PMID:Enzyme and immunohistochemical phenotyping of diethylnitrosamine-induced liver lesions of male C3H/He, B6C3F1 and C57BL/6J mice. 157 19

Exposure to chlordecone (CD, Kepone) is known to increase the hepatotoxicity of chloroform (CHCl3) in rats. A time-course analysis was conducted relating several indices of biotransformation capacity with the ability of CD to potentiate CHCl3-induced hepatotoxicity. Male Sprague-Dawley rats were given a single administration of corn oil alone or CD (50 mg/kg, po) dissolved in corn oil. At 2, 4, 8, 16, 20, 24, or 32 days posttreatment, groups of rats were killed and their livers were analyzed for (i) cytochrome P-450, NADPH-dependent cytochrome c reductase, cytochrome b5 and glutathione content or (ii) in vitro irreversible binding of 14CHCl3-derived radiolabel to microsomal protein. Similarly treated rats were challenged (2-32 days posttreatment) with CHCl3 (0.5 mL/kg po); 24 h later, liver damage was assessed by plasma alanine aminotransferase (ALT), plasma ornithine carbamyl transferase (OCT), plasma bilirubin, and hepatic glucose-6-phosphatase. CD potentiation was maximal 2 days posttreatment; and enhanced susceptibility to CHCl3 persisted up to 20-24 days post-CD treatment. In a parallel study animals treated with chlordecone were killed 8, 16, 20, 24, or 32 days later. Blood, kidney, liver, and adipose tissue samples were taken and analyzed for chlordecone content. The results suggest that a general temporal correlation exists between biotransformation rate (microsomal 14C binding), chlordecone content, and the severity of liver injury; the other parameters monitored do not appear to relate directly to the potentiation.
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PMID:Temporal relationships between biotransformation, detoxication, and chlordecone potentiation of chloroform-induced hepatotoxicity. 242 14

The effects of carbon disulfide (CS2) on the liver microsomal drug-metabolizing enzyme system and other enzyme activities were studied 1 hr after the oral administration of 3-300 mg/kg of CS2 in mice. Considerable decreases in drug-metabolizing enzyme activities (such as hydroxylation of aniline, O-dealkylation of p-nitroanisole, 7-ethoxycoumarin and 7-ethoxyresorufin, and N-demethylation of N,N-dimethylaniline), NADPH-cytochrome P-450 reductase (but not NADPH-cytochrome c reductase), and P-450-associated peroxidase activities were already observed at 3 and 30 mg/kg of CS2, dose dependently. At the same dosage levels, the magnitudes of microsomal spectral changes induced by aniline and nicotinamide (type 2 substrates), but not those induced by hexobarbital and SKF-525A (type 1 substrates), were also reduced to a considerable extent. The degrees of these alterations were all greater than that of the measurable loss of P-450 content, i.e. the loss of functional activity of P-450 was much greater than simply expected from the apparent decrease in the hemoprotein content. Cytochrome b5 content and NADH-ferricyanide reductase activity were unchanged at 30 and 300 mg/kg of CS2, although NADH-cytochrome c reductase activity was increased at the latter dose. The following enzyme activities did not change significantly at up to 300 mg/kg of CS2: flavin-containing monooxygenase, UDP-glucuronyl transferase, glucose-6-phosphatase and heme oxygenase in microsomes, and glutathione S-transferases in the soluble fraction. Microsomal conjugated diene levels and liver glutathione content were also unchanged. These observations support the theory that P-450 is a sensitive and selective site for CS2 action, where CS2 itself is bioactivated. It was also shown that the loss of P-450 was reversible after a single, or repeated, administration of CS2.
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PMID:Early, selective and reversible suppression of cytochrome P-450-dependent monooxygenase of liver microsomes following the administration of low doses of carbon disulfide in mice. 377 18

Effects of medroxyprogesterone acetate (MPA) on hepatic glucose handling and drug metabolism were investigated in female rats with intact and damaged liver. Hepatic glucose-6-phosphatase activity, glycogen content and fasting blood glucose were assessed as indices of glucose metabolism. Cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were assayed to reflect liver drug metabolism. Liver injury was induced by dimethylnitrosamine and carbon tetrachloride. The results demonstrate that hepatic glucose handling and drug metabolism were changed in a parallel fashion in intact, damaged and induced liver. The MPA-induced changes in glucose metabolism were slight in intact animals, whereas the compound has an increasing effect on glucose and drug metabolism in rats with damaged liver. The findings demonstrate the MPA enhances the normallization of hepatic glucose and drug metabolism in damaged liver.
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PMID:Effects of medroxyprogesterone acetate on hepatic glucose metabolism and microsomal enzyme activity in rats with normal and altered liver. 632 13

The influence of Liv.100 on the hepatotoxicity of antituberculosis drugs [isoniazid (INH), rifampicin (RMP) pyrazinamide (PZA)] was studied in male albino rats. INH, RMP, and PZA were proved to be the most hepatotoxic. Rats were treated with antituberculosis drugs daily for a period of 6 weeks by intragastric administration. The combined use of antituberculosis drugs elevated the levels of cytochrome P-450 and cytochrome-b5. A significant increase was observed in the levels of NADPH-cytochrome P-450 reductase and NADH-cytochrome-b5 reductases after antitubercular drug administration. During antitubercular drug treatment a significant decrease was also observed in the activity of glucose-6-phosphatase. The extent of NADPH-induced and ascorbic acid-induced lipid peroxides were marked in antitubercular drug treatment, when compared with normal control animals. Oral Liv.100 co-administration, for the same period, modulated the alterations in the xenobiotic metabolizing system and microsomal lipid peroxidation in experimental animals. The results are discussed with reference to drug metabolizing enzymes, lipid peroxidation and the hepatoprotective nature of Liv.100.
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PMID:Modulating effect of Liv.100, an ayurvedic formulation on antituberculosis drug-induced alterations in rat liver microsomes. 1153 79