Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.49 (glucose-6-phosphate dehydrogenase)
 7,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cDNA for the X-chromosome encoded human glucose-6-phosphate dehydrogenase (G6PD) has been expressed in E. coli and the enzyme purified to homogeneity, using a simple one-step fractionation on 2'5'-ADP-Sepharose. By selecting one of several different expression vectors and by optimizing culture conditions a yield of more than 10 mg of pure enzyme per liter of culture is obtained reproducibly. When the recombinant enzyme and authentic G6PD purified from normal human red cells were compared, they proved to be indistinguishable by the following criteria: electrophoretic mobility in both native and denaturing conditions, the Km values for glucose 6-phosphate and NADP and the Ki value for NADPH. The recombinant enzyme, unlike the red cell enzyme, retained 100% activity when stored at 4 degrees C for over 1 year.
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PMID:Purification and properties of human glucose-6-phosphate dehydrogenase made in E. coli. 154 Jun 38

Studies were performed to determine the effects of chronic hypoxia on enzymes that catalyze various detoxication reactions. Rats were exposed to room air or 10.5% O2 for 10 days, and microsomes and postmicrosomal supernatants were isolated from liver. Detoxication enzyme activities were measured by radiochemical and spectrophotometric assays, and immunoreactive protein amounts were measured by Western blot analysis. Total cytochrome P450, as measured by the CO-difference spectrum, and activities of superoxide dismutase (EC 1.15.1.1), epoxide hydrolase (EC 4.2.1.63), catalase (EC 1.11.1.6), glutathione disulfide reductase (EC 1.6.4.2), and glutathione (GSH) S-transferase (EC 2.5.1.18) were not affected by this extent of hypoxia. In contrast, 10 days of hypoxia decreased activities or immunoreactivities (% of aerobic) of GSH peroxidase (EC 1.11.1.9) (54%), cytochrome P450EtOH2 (42%), CYP3A1 (53%), sulfotransferase (EC 2.8.2.1) (77%) and UDP-glucuronosyltransferase (EC 2.4.1.17) (65%). Activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), an important enzyme in NADPH production was also decreased to 56% of the aerobic value, but Western blot analysis showed that the amount of protein reactive with antibodies to glucose-6-phosphate dehydrogenase was not affected by hypoxia. Thus, hypoxia may decrease activity of enzymes by regulatory mechanisms even though the amount of immuno-detectable enzyme is unchanged. Liver cells isolated from rats exposed to hypoxia also gave lower GSH synthetic rates than cells from normoxic rats. This result, together with the effect of hypoxia on glucose-6-phosphate dehydrogenase, indicates that the GSH supply for GSH-dependent detoxication reactions may be limited due to chronic hypoxia. To test directly whether chronic hypoxia increased sensitivity to a compound normally detoxified by a GSH-dependent reaction, sensitivity to tert-butyl hydroperoxide (t-BuOOH) of hepatocytes from rats exposed to in vivo hypoxia was compared to that from normoxic rats. The results showed that the cells from the hypoxic rats were much more sensitive to injury. Taken together, these results suggest that decreases in amounts and/or activities of detoxication enzymes during chronic hypoxia may result in increased susceptibility of cells to chemical injury.
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PMID:Effect of chronic hypoxia on detoxication enzymes in rat liver. 161 Apr 6

Fumarase C was strongly induced by paraquat in a parental strain of Escherichia coli but was not induced in a strain lacking the soxRS response. Moreover, a strain that constitutively expresses the soxRS regulon contained more fumarase C than did the parental strain. The Mn-containing superoxide dismutase and glucose-6-phosphate dehydrogenase, members of the soxRS regulon, were similarly induced by paraquat. Mutational defects in glucose-6-phosphate dehydrogenase increased the induction of fumarase C by paraquat. For Mn-containing superoxide dismutase, responsiveness to paraquat was also enhanced in the glucose-6-phosphate dehydrogenase-defective strains. Overproduction of the Mn-containing superoxide dismutase, elicited by isopropyl beta-D-thiogalactoside in a tac-sodA fusion strain, did not diminish induction of fumarase C or of glucose-6-phosphate dehydrogenase by paraquat, and induction of these enzymes was more sensitive to paraquat when the cells were growing on succinate rather than on LB medium. These results indicate that fumarase C is a member of the soxRS regulon and that this regulon does not respond to changes in O2- concentration but perhaps does respond to some consequence of a decrease in the ratio of NADPH to NADP+.
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PMID:Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon. 163 Oct 70

We used immunocytochemical staining to localize the RLM6 form of cytochrome P-450 in rat brain. Immunofluorescence staining in vibratome sections was positive in cells that resembled oligodendrocytes, which are the cells that synthesize and maintain myelin. Double immunofluorescence staining with anti-RLM6, plus mouse monoclonal antibodies (MAb) against 2',3'-cyclic nucleotide-3'-phosphohydrolase or galactocerebrosides, showed localization of each of these oligodendrocyte "markers" in the same cells as RLM6. In vibratome sections from brains of adult rats there was faint RLM6 immunostaining in some of the myelinated fibers as well as in oligodendrocytes. In paraffin sections from adult rat brains, myelinated tracts were RLM6 positive, as were oligodendrocytes and myelinated fibers in the gray matter. Oligodendrocytes were also shown to contain glucose-6-phosphate dehydrogenase. We suggest that RLM6, which is constitutive to liver, is also constitutive to brain and, via the acetone monooxygenase reaction, which also utilizes NADPH, may contribute to the conversion of ketone bodies to substrates that could provide energy for the synthesis and maintenance of myelin.
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PMID:Immunocytochemical staining of the RLM6 form of cytochrome P-450 in oligodendrocytes and myelin of rat brain. 164 55

Asbestosis is characterized by an alveolar macrophage alveolitis with injury and fibrosis of the lower respiratory tract. Alveolar macrophages recovered by bronchoalveolar lavage spontaneously release exaggerated amounts of oxidants including superoxide anion and hydrogen peroxide that may mediate alveolar epithelial cell injury. Dehydroepiandrosterone (DHEA) is a normally occurring adrenal androgen that inhibits glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate shunt necessary for NADPH generation and superoxide anion formation. In this regard, we hypothesized that DHEA may reduce asbestos-induced oxidant release. DHEA added in vitro to alveolar macrophages lavaged from 11 nonsmoking asbestos workers significantly reduced superoxide anion release. DHEA was measured in bronchoalveolar lavage and found to be similar to serum concentrations. DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis of the lower respiratory tract.
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PMID:Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis. 165 Dec 23

A model of liver hyperplastic noduligenesis was induced in rats in vivo by long-term administration of thioacetamide (TAM; 100 mg/kg day i.p.). Three doses of 50 mg/kg of an antitumoral rhodium(III) complex were administered at 14, 9 and 5 days before the end of TAM treatment. Blood and liver were obtained from either TAM, Rh(III) complex or TAM plus Rh(III) complex-treated rats in order to determine the interaction of both (tumoral and antitumoral) substances with the biochemical pathways related to glutathione redox cycle, enzyme activities involved in the oxidative stress coupled to the NADPH/NADP pair and enzymes related to the mono-oxygenase P450 system. The results showed that TAM induced an imbalance between the activities of glutathione-coupled enzymes. Glutathione reductase activity increased along with the intoxication, while glutathione peroxidase activity decreased. Alterations in the activity of soluble glutathione peroxidase were parallel to those of catalase. These results, together with decreased activities of enzymes related to cytochrome P450 mono-oxygenase system, NADPH cytochrome P450 reductase and NADH cytochrome b5 reductase, suggest that liver cells are not protected against the peroxidative stress produced by chronic administration of TAM. The Rh(III) complex did not produce significant changes in the parameters assayed when administered alone. When this complex was administered to TAM-treated rats, significant restoration of the following activities was observed: those of NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and malic enzyme), that of glutathione reductase (NADPH-consuming enzyme), NADPH-cytochrome P450 reductase and total catalase. These results, together with others in previous studies, suggest that the altered liver function induced by chronic administration of TAM can be partially restored by this rhodium complex. The mechanisms by which this complex counteracts the TAM-induced changes have not yet been established.
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PMID:Alterations in hepatic peroxidation mechanisms in thioacetamide-induced tumors in rats. Effect of a rhodium(III) complex. 167 54

The effect of hyperthyroidism on liver glutathione (GSH) metabolism was studied in fed rats after the administration of 0.1 mg T3/kg body wt, for 1-3 consecutive days. T3-calorigenesis resulted in elevated rates of O2 consumption by the liver, together with higher lipid peroxidative processes and GSH depletion, compared to the euthyroid state. The study of the enzymes related to GSH metabolism revealed no significant changes in the activity of glutathione peroxidase and glutathione reductase, with decreases (27-41%) in the activity of glutathione-S-transferases and marked elevation (133%) in that of gamma-glutamyl transferase, 3 days after T3 treatment. At this experimental time, the activity of the NADPH generating enzyme glucose-6-phosphate dehydrogenase was enhanced by 84% in the liver of T3-treated rats, compared to that in the controls. In these conditions, the canalicular efflux of GSH was not altered by T3, whereas net and fractional rates of sinusoidal GSH efflux were enhanced by 86% and 288%, respectively. The latter effect of hyperthyroidism was found in parallel with an enhancement in sinusoidal lactate dehydrogenase and protein release, suggesting that loss of GSH might be related to a permeabilization of the hepatocyte plasma membrane. Liver GSH turnover assessed after a pulse of [35S]cysteine resulted in a 209% increase in the fractional turnover rate in hyperthyroid rats over controls, under steady state conditions for both hepatic GSH pools, leading to a 62% enhancement in the respective turnover flux. Data suggest that the elevation in the sinusoidal GSH efflux from the liver and in the hepatic capacity to degrade the tripeptide are major mechanisms leading to GSH depletion in the liver of T3-treated rats. As the increased GSH use is not balanced by the elevation in GSH synthesis, a lower steady state level of GSH is attained in the liver.
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PMID:Effects of hyperthyroidism on rat liver glutathione metabolism: related enzymes' activities, efflux, and turnover. 167 89

Role of mono-oxygenases as a mechanism of resistance to the synthetic pyrethroid, deltamethrin in the larvae of Culex quinquefasciatus Say, Aedes aegypti L. and Anopheles stephensi Liston developed by laboratory selections with deltamethrin, DDT or deltamethrin and the synergist, piperonyl butoxide (PBO) in the ratio of 1:5, was investigated. There was a significant correlation with mono-oxygenase activity and larval LC50 to deltamethrin in various strains of all the three species. In addition, the activity of glucose-6-phosphate dehydrogenase (G6PD), the main NADPH generating enzyme for mono-oxygenases, also showed enhanced activity in deltamethrin and DDT-selected strains. The present data, therefore, clearly suggest that deltamethrin resistance in the larvae of Cx. quinquefasciatus, Ae. aegypti and An. stephensi is mainly due to the detoxification of deltamethrin by microsomal mono-oxygenases. High activity of G6PD observed in DDT-selected strains seems to be related to its role as a rate-limiting enzyme in GSH-dependent dehydrochlorination of DDT.
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PMID:Involvement of mono-oxygenases as a major mechanism of deltamethrin-resistance in larvae of three species of mosquitoes. 167 32

Rainbow trout, Oncorhynchus mykiss, were used to evaluate the effects of carbohydrate loading on plasma levels of pancreatic hormones and associated changes in metabolic indexes in a carnivorous fish. Glucose (3,000 mg/dl, 10 microliters/g body wt) was injected intraperitoneally into fish (mean wt 54 +/- 5 g) that were killed 0.5-24 h after administration. Glucose injection resulted in hyperglycemia with maximum glucose levels of 306 +/- 13 mg/dl observed 60 min after injection. Glucose administration also resulted in hyperlipidemia. Plasma fatty acids increased twofold in glucose-injected animals. Alterations in plasma metabolites reflected changes in energy stores. Although total lipid concentration was unaffected by glucose injection, lipolytic enzyme activity in the liver was enhanced. Biosynthetic capacity, as indicated by NADPH production from glucose-6-phosphate dehydrogenase, was decreased by glucose injection. Liver glycogen content was reduced in glucose-injected animals 1 h after injection. Glucose injection was attended by increases in the plasma levels of gene II somatostatin-25 (predominant form of pancreatic somatostatin in salmonids) and of glucagon. Insulin levels were initially suppressed after glucose injection. These results indicate that metabolic adjustments caused by glucose administration can be related to the regulatory action of pancreatic hormones. Furthermore, these results suggest that the somatostatin-secreting cells of the trout are sensitive to glucose and that somatostatin-suppressed insulin secretion contributes to the glucose intolerance of trout.
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PMID:Insulin suppression is associated with hypersomatostatinemia and hyperglucagonemia in glucose-injected rainbow trout. 167 8

Previous studies from our laboratory have shown that dehydroepiandrosterone (DHEA), an inhibitor of glucose-6-phosphate dehydrogenase (G6PD), prevents the development of gamma-glutamyltranspeptidase (GGT)-positive foci in the early stages of hepatocarcinogenesis in rats. Since high rates of DNA and cholesterol (CH) synthesis are observed during promotion of carcinogenesis, and mevalonate (MVA), or some other intermediates of CH synthesis, could be mediators of DNA synthesis, we investigated the effect of DHEA on CH synthesis in rat liver during the development of GGT-positive foci. Hepatocarcinogenesis was induced by diethylnitrosamine in female Wistar rats by the Solt-Farber protocol (initiation/selection) with and without phenobarbital treatment. A 15 day treatment with DHEA (0.6% in the diet), started after selection, caused a great fall in labeling and mitotic indices of GGT-positive foci, which was prevented by the simultaneous administration of a mixture of four deoxyribonucleosides (DRNs) of adenine, guanine, cytosine and thymine or four ribonucleosides (RNs) of adenine, guanine, cytosine and uridine, but not by the corresponding bases. DHEA greatly inhibited G6PD activity and the production of ribulose-5-phosphate, without affecting NADPH levels, due to the compensatory increase in malic enzyme and isocitric dehydrogenase activities. Serum lecithin/cholesterol acyltransferase activity underwent a reduction in conditions allowing a rapid growth of GGT-positive tissue (absence of DHEA or presence of DHEA plus DRNs or RNs). Liver slices isolated from DHEA-treated rats showed a rise in CH content, coupled with a 80% fall in the incorporation of labeled acetate, but not of labeled MVA, into CH. A 25 day treatment of rats subjected to initiation/selection, started after the appearance of persistent nodules, caused a 36 and 78% fall in the incorporation, in vivo, of 3H2O into nodular and surrounding liver CH respectively. DRN did not counteract DHEA-induced inhibition on CH synthesis. Thus DHEA inhibits the CH biosynthetic pathway before MVA synthesis, in conditions (presence of DHEA plus DRN/RN) allowing rapid growth of preneoplastic lesions. Therefore, the development of these lesions does not need the synthesis of large amounts of CH and CH metabolites. Thus, the antipromotion effect of DHEA may depend on a decreased availability of pentose phosphates for DNA synthesis.
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PMID:Differential effects of dehydroepiandrosterone and deoxyribonucleosides on DNA synthesis and de novo cholesterogenesis in hepatocarcinogenesis in rats. 168 32


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