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)

Primary monolayer culture of adult rat hepatocytes represents a novel and potentially useful technique to study many aspects of hepatic physiology for extended periods of time in vitro (J Cell Biol 59:722-734, 1973). In examining the hepatic drug-metabolizing system in these cells, we have discovered that the conditions of cell culture exert rapid, selective, and reproducible changes in microsomal enzymes. In the 24- to 48-hr period immediately following preparation and culture of the isolated parenchymal cells, the level of the drug-binding microsomal hemoprotein, cytochrome P-450, measured in extracts of cell homogenates, declined to less than 20% of its in vivo level, whereas NADPH-cytochrome c reductase activity was only moderately reduced and glucose-6-phosphatase activity remained unchanged. The activity of aminopyrine-N-demethylase and aniline hydroxylase also fell, paralleling the level of cytochrome P-450. By contrast, p-nitroanisole O-demethylase activity was unchanged in the cultured hepatocytes despite evidence (type I binding spectrum, NADPH requirement, inhibition by carbon monoxide or by SKF 525A) that p-nitroanisole O-demethylase is a cytochrome P-450-dependent enzyme. In culture, as in vivo, aromatic polycyclic hydrocarbons stimulated p-nitroanisole O-demethylase and aryl hydrocarbon (benzo [a] pyrene) hydroxylase activities; however, this effect was unaccompanied by a detectable increase in total carbon monoxide-binding hemoprotein. The data indicate that the profile of microsomal oxidase enzymes and their control undergo striking changes as hepatocytes adapt to cell culture.
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PMID:Drug metabolism in adult rat hepatocytes in primary monolayer culture. 40 8

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.
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PMID:Enhanced metabolism and mutagenesis of nitrosopyrrolidine in liver fractions isolated from chronic ethanol-consuming hamsters. 57 Aug 82

Antibodies against cytochrome P-450 are found in some children with autoimmune hepatitis (antiliver/kidney microsome 1) and in patients with ticrynafen hepatitis (antiliver/kidney microsome 2). For an immune reaction against cytochrome P-450 to possibly destroy the hepatocytes, one must assume that cytochrome P-450 is present on the plasma membrane surface of hepatocytes. In a first series of experiments, plasma membranes were prepared with a technique based on the electrostatic attachment of isolated hepatocytes to polyethyleneimine-coated beads. After vortexing, beads were coated with a very pure plasma membrane fraction. Microsomal contamination, judged from the specific activities of glucose-6-phosphatase or NADH-cytochrome c reductase, was less than 1%. Nevertheless, the specific content (per milligram of protein) of CO-binding cytochrome P-450 was 20% of that in microsomes; the specific benzo(a)pyrene hydroxylase activity was 25%, and ethoxycoumarin deethylase 11%. Immunoblots showed the presence of cytochromes P-450 UT-A, UT-H, PB-B, ISF-G and PCN-E, the last three isoenzymes being inducible by, respectively, phenobarbital, 3-methylcholanthrene and dexamethasone. In a second series of experiments, nonpermeabilized isolated hepatocytes from untreated rats were incubated with anticytochrome P-450 antibodies. Immunofluorescence and immunoperoxidase staining confirmed the presence of cytochromes P-450 UT-A, PB-B and ISF-G on the membrane. In a last series of experiments, human antiliver-kidney microsomal 1 antibodies were found to react specifically with rat liver plasma membrane cytochrome P-450 UT-H (IID subfamily). We conclude that several cytochrome P-450 isoenzymes are present, active and inducible on the plasma membrane surface of hepatocytes. It is therefore conceivable that immunization against plasma membrane cytochrome P-450 might lead to the immunological destruction of hepatocytes in some patients.
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PMID:Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane. 211 12

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.
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PMID:Hepatic microsomal cytochrome P450 system during experimental hookworm infection. 236 36

The cholesterol content of rat liver microsomal membranes was modified in vitro by incubating microsomes and cytosol with liposomes prepared by sonication of microsomal lipids and cholesterol. In this way, the cholesterol to phospholipid molar ratio was increased from 0.11-0.13 in untreated microsomes to a maximal of 0.8 in treated ones. Cholesterol incorporation in microsomes produced an increase in the diphenyl-hexatriene steady-state fluorescence anisotropy and a decrease in the efficiency of pyrene-excimer formation which indicated a decrease in the rotational and translational mobility, respectively, of these probes in the membranes lipid phase. Cholesterol incorporation in microsomes did not affect significantly the glucose-6-phosphatase activity in 0.1% Triton X-100 totally disrupted microsomes, but diminished the glucose-6-phosphatase activity of 'intact' microsomes. This indicates that possibly the glucose 6-phosphate translocation across the microsomal membrane is impeded by an increase in the membrane apparent 'microviscosity'. Cholesterol incorporation in microsomes decreased NADH-cytochrome c reductase without affecting NADH-ferricyanide reductase activity. The delta 9 desaturation reaction rate was enhanced by cholesterol incorporation at low but not at high palmitic acid substrate concentration. delta 5 and delta 6 desaturase reaction-rates were increased both at low and high fatty acid substrate concentrations. These results suggest that a mechanism involving fatty acid desaturase enzymes, might exist to self-regulate the microsomal membrane lipid phase 'fluidity' in the rat liver.
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PMID:In vitro modification of cholesterol content of rat liver microsomes. Effects upon membrane 'fluidity' and activities of glucose-6-phosphatase and fatty acid desaturation systems. 299 32

Sonic disrupted mitoplasts from 3-methylcholanthrene (MCA) treated rats can catalyze the formation of benzo(a)pyrene (BaP) adducts with calf thymus DNA in the presence of an NADPH generating system. The mitoplasts used in this study contained less than 1% microsomal marker enzymes: rotenone insensitive NADPH cytochrome c reductase and glucose-6-phosphatase. The rates of BaP metabolism and DNA adduct formation per nanomole cytochrome P-450 were different for MCA induced mitochondrial and microsomal enzymes. The major B(a)P DNA adducts formed in incubations with lysed mitoplasts were derived from reaction of 9-OH-B(a)P-4,5 oxide with deoxyguanosine. The results suggest a potential role of mitochondrial monooxygenase activity in the covalent binding of B(a)P to mitochondrial DNA.
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PMID:Formation of benzo(alpha)pyrene metabolites and DNA adducts catalyzed by a rat liver mitochondrial monooxygenase system. 299 32

Plasmodium yoelii nigeriensis infection in albino mice significantly altered the hepatic microsomal mixed function oxidase system. Cytochrome P-450 (the terminal monooxygenase) and other monooxygenases, viz. aniline hydroxylase, aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase were significantly lowered while microsomal heme showed 4-fold increase at 80% parasitaemia. Noticeable impairment in the other components like NADH:cytochrome b5 reductase, NADPH:cytochrome c reductase, cytochrome b5 and glucose-6-phosphatase was also observed. Oral treatment of normal and P. y. nigeriensis infected mice with chloroquine (64 mg per kg body weight for 4 days) caused lowering of mixed function oxidase activities which however showed a recovering trend, a week after cessation of treatment.
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PMID:Effect of Plasmodium yoelii nigeriensis infection and chloroquine on the hepatic mixed function oxidase system of mice. 362 73

Polycyclic hydrocarbon metabolism in male Sprague-Dawley rats following inhalation of aerosolized cadmium chloride (CdCl2) was examined. Constitutive activity of microsomal aryl hydrocarbon hydroxylase (AHH) (benzo(a)pyrene substrate) was monitored in lung and liver homogenates up to 10 days after exposure. Lung AHH activity was reduced by 85% during the first 2 days following cadmium inhalation, and did not return to normal levels until 7 days after exposure. Enzyme activity in the livers of cadmium-treated animals was similarly depressed (by 65%) within 24 hr. Cadmium inhalation also inhibited (by 50%) 3-methylcholanthrene (MC) induction of lung AHH when compared with MC-treated controls. No significant effect on AHH inducibility by MC was noted in liver homogenates from cadmium-exposed animals. Nonspecific microsomal damage appeared not to occur since glucose-6-phosphatase activity in lung was unaffected by cadmium treatment. Although the mechanism of cadmium's action remains unclear, it appears not to involve a direct interaction of the metal with enzyme. The alteration of AHH activity by cadmium may result from injury to a specific cell type within the lung, which may be a major site of pulmonary AHH activity, or may result from modulation of synthesis and/or degradation of heme proteins in the lung. These results suggest that cadmium, under these conditions, markedly reduces the constitutive and inducible activity of AHH in the lung.
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PMID:Lung aryl hydrocarbon hydroxylase: inhibition following cadmium chloride inhalation. 631 93

n-Butyl and isoamyl alcohols decrease the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene and enhance the efficiency of pyrene excimer formation when these probes are incorporated in rat-liver microsomal membrane, suggesting an increase in rotational and translational mobilities. Neither alcohol modifies NADH-ferricyanide reductase activity but both increase NADH-cytochrome c reductase activity. This was interpreted as an increase in the rate of lateral diffusion of the proteins cytochrome b5 and cytochrome b5 reductase as a consequence of the enhanced membrane lipid phase fluidity. Microsomal delta 9 and delta 6 desaturase activities in the presence of isoamyl alcohol were also studied. This alcohol decreases delta 9 desaturation when it is measured at a low substrate concentration (13 microM palmitic acid), but it is not modified when it is measured at a high substrate concentration (66 microM palmitic acid). delta 6 desaturation is diminished by isoamyl alcohol when it is measured with both 13 microM and 66 microM linoleic acid. The influence of isoamyl alcohol on the glucose-6-phosphatase system activity was also studied. In non-detergent-treated microsomes, isoamyl alcohol enhances glucose-6-phosphatase activity. However, if microsomes are previously treated with 0.1% Triton X-100 isoamyl alcohol does not modify this activity. The enhancement of the glucose 6-phosphate transport rate is not due to membrane permeability barrier disruption, since isoamyl alcohol does not modify mannose-6-phosphohydrolase latency. This would suggest that an increase in membrane lipid phase fluidity specifically activates glucose 6-phosphate transport across the membrane.
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PMID:Short-chain aliphatic alcohols increase rat-liver microsomal membrane fluidity and affect the activities of some microsomal membrane-bound enzymes. 631 21

Adult male rats receiving styrene by gavage (200 or 400 mg kg-1, 6 days a week) for 100 days exhibited a significant dose-dependent increase in hepatic benzo[a]pyrene hydroxylase and aminopyrine-N-demethylase, a decrease in glutathione-S-transferase and no change in glucose-6-phosphatase. A decrease in the activity of mitochondrial succinic dehydrogenase and beta-glucuronidase was also observed. Activity of acid phosphatase was decreased only at the higher dose level. Levels of serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were elevated only at the higher dose level. The absolute and relative weights of the liver of control and treated animals showed no significant difference. Histopathological studies of the liver tissue revealed tiny areas of focal necrosis, consisting of few degenerated hepatocytes and inflammatory cells at the higher dose level only.
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PMID:Hepatic effects of orally administered styrene in rats. 718 5


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