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:1.1.1.49 (glucose-6-phosphate dehydrogenase)
7,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oscillations in glyceraldehyde-3-phosphate dehydrogenase (GAPD) and glucose-6-phosphate dehydrogenase (G6PD) activities were recorded in suspensions of intact human red blood cells (RBCs) exposed to various light regimens. The periods of these oscillations, defined as "long ultradian," ranged between 13 and 18 h regardless of light regimen. The patterns of enzymatic activities were the same when assayed at each time point, in full hypotonic hemolysates, and membrane-free hemolysates. However, if hemolysates were prepared by sonication the activity pattern did not exhibit significant oscillations and the activity was higher than that recorded in hypotonic hemolysates. The observed rhythms may reflect a time-dependent attachment and detachment of enzyme molecules from cell membrane, suggesting that at the bound state the enzyme molecules are (temporarily) inactive. Oscillations with similar long ultradian periods were also observed in Ca++ concentration of suspended RBCs and in the binding of Ca++45 to human RBC ghosts. Treatment of the RBCs with A2C or Diamide before the preparation of the ghosts changed or distorted the rhythmic pattern of Ca++45 binding. These results point to the role of the membrane in processing the long ultradian oscillations. The relation between this type of oscillations to circadian rhythm is discussed.
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PMID:Long ultradian rhythms in red blood cells and ghost suspensions: possible involvement of cell membrane. 224 61

Anaerobically grown Escherichia coli accumulate active manganese-containing superoxide dismutase (MnSOD) upon exposure to diamide. This induction requires de novo biosynthesis of MnSOD. Catalase, glutathione disulfide reductase, and glucose-6-phosphate dehydrogenase were also induced by diamide in anaerobic E. coli. A GSH-negative strain of E. coli did not produce MnSOD under anaerobic conditions and was as responsive to diamide as was the wild type strain. Diamide which had been prereduced, by incubation with GSH, was ineffective. NO3- plus paraquat, which elicits increased anaerobic biosynthesis of the MnSOD polypeptide, but not of active MnSOD, synergized with diamide in the induction of active MnSOD. A similar increase in the ability of diamide to cause anaerobic biosynthesis of active MnSOD was seen when the production of the MnSOD polypeptide was increased by isopropyl-beta-D-thiogalactopyranoside, in a strain bearing the MnSOD gene under the control of the tac promoter. These results are explained in terms of a dual action of diamide, i.e. at both the transcriptional and the maturational levels of biosynthesis of MnSOD. Oxidative inactivation of an Fe(II)-containing repressor and oxidative facilitation of insertion of manganese, in place of iron, into the nascent MnSOD polypeptide, are the postulated bases of this dual action.
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PMID:Anaerobic biosynthesis of the manganese-containing superoxide dismutase in Escherichia coli. Effects of diazenedicarboxylic acid bis(N,N'-dimethylamide) (diamide). 225 40

Thiol status and growth in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes. Experimental Parasitology 57, 239-247. The relationship of the thiol status of the human erythrocyte to the in vitro growth of Plasmodium falciparum in normal and in glucose-6-phosphate dehydrogenase (G6PD)-deficient red cells was investigated. Pretreatment with the thiol-oxidizing agent diamide led to inhibition of growth of P. falciparum in G6PD-deficient cells, but did not affect parasite growth in normal cells. Diamide-treated normal erythrocytes quickly regenerated intracellular glutathione (GSH) and regained normal membrane thiol status, whereas G6PD-deficient cells did not. Parasite invasion and intracellular development were affected under conditions in which intracellular GSH was oxidized to glutathione disulfide and membrane intrachain and interchain disulfides were produced. An altered thiol status in the G6PD-deficient erythrocytes could underlie the selective advantage of G6PD deficiency in the presence of malaria.
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PMID:Plasmodium falciparum: thiol status and growth in normal and glucose-6-phosphate dehydrogenase deficient human erythrocytes. 637 52

We have studied the nature of the oxidative lesion of the erythrocyte membrane in glucose-6-phosphate dehydrogenase (G6PD) mutants with chronic hemolysis, comparing these membranes with those from normal red cells (RBC) subjected to oxidative stress in vitro. Disulfide-linked polypeptide aggregates are found in membranes from fresh RBC of these G6PD mutants and from aerobically incubated normal erythrocytes. As further evidence of oxidative damage, increased disulfide bonds were found in the RBC membranes from both the mutants and incubated normal RBC. The intermolecular bonds which cross-link membrane polypeptides to form the observed aggregates, however, only accounted for a fraction of the membrane disulfide bonds present. Thus, most of the disulfide bonds in the G6PD mutants were intramolecular. These intramolecular disulfide bonds were widely distributed on the membrane polypeptides, but were found to be concentrated on cytoskeletal anchoring proteins, bands 2.1-2.3, using [14C] iodoacetamide labelling of the sulfhydryls involved in disulfide bonds. The intermolecular bonds, on the other hand, were concentrated in spectrin. When G6PD mutant membranes were examined on sucrose density gradients, a subpopulation of dense membranes was observed which resembled the membranes of oxidatively stressed normal RBC both in increased density and in increased binding of nonhemoglobin cytoplasmic protein. To study the relationship between sulfhydryl oxidation, membrane density and RBC viscosity the sulfhydryl oxidant diamide (diazine dicarboxylic acid bis-[dimethylamide]) was used. Diamide treated erythrocytes, like the G6PD mutants, had decreased GSH, increased polypeptide aggregates, increased viscosity, but no change in ATP. We conclude that in G6PD mutants with chronic hemolysis oxidative damage includes aggregate formation due to intermolecular disulfide bonds, and intramolecular disulfide bond formation associated with increased binding of non-hemoglobin cytoplasmic proteins to the membrane. The relative importance of intermolecular and intramolecular disulfide bond formation and the mechanism whereby these changes may produce decreased RBC deformability and survival remain to be determined.
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PMID:Mechanisms of decreased erythrocyte deformability and survival in glucose 6-phosphate dehydrogenase mutants. 733 11

Transcriptional regulation of the sodA gene, a member of the soxRS regulon encoding the manganese-containing superoxide dismutase (MnSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) of Escherichia coli, was examined in a variety of regulatory mutants. Diamide, an oxidant that causes the anaerobic biosynthesis of the MnSOD polypeptide and also facilitates insertion of manganese at the active site, was found to anaerobically induce MnSOD in both soxRS and fur arcA fnr strains. Metal chelating agents also caused anaerobic induction of MnSOD in a fur arcA fnr triple mutant; however, this induction of MnSOD and of glucose-6-phosphate dehydrogenase (G6PD) by 1,10-phenanthroline was dependent on an intact soxRS locus. A strain of E. coli bearing a fusion of the soxS promoter to lacZ was used to demonstrate that both diamide and 1,10-phenanthroline caused anaerobic activation of soxS transcription. These results indicate that (i) both diamide and 1,10-phenanthroline induce the soxRS regulon anaerobically by stimulation of soxS transcription; (ii) diamide, but not metal chelators, also induces MnSOD biosynthesis by a soxRS-independent mechanism, perhaps mediated by effects on fur, arcA, or fnr-mediated repression of sodA; and (iii) the soxRS locus contains a metal-binding component and is responsive to the redox status of the cell.
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PMID:Induction of manganese-containing superoxide dismutase in anaerobic Escherichia coli by diamide and 1,10-phenanthroline: sites of transcriptional regulation. 846 Jan 39

Direct oxidation of embryonic reduced glutathione (GSH) by a thiol oxidant, diamide, has been demonstrated to result in increased glutathione disulfide (GSSG) and protein-glutathione mixed disulfide (protein-S-SG) formation, which is accompanied by embryotoxicity and reductions in amniotic fluid volume. The altered functions of critical proteins or enzymes caused by the formation of protein-S-SG perturb cellular metabolism and may be involved in the embryotoxicity produced by GSH oxidation. The present study investigates changes in the metabolism of glucose through glycolysis and the pentose phosphate shunt pathways (PPP) and their related enzymes under the oxidative conditions produced by diamide exposure in organogenesis-stage rat conceptus (gestational day 10) in vitro. The metabolism of glucose via the PPP, measured as amounts of CO2 production from D-[1-14C]-glucose, was significantly increased in the conceptus exposed to 100-500 microM diamide to levels 2.5-3-fold those of controls. It was found that these substantial increases in the PPP activity did not correlate well with a moderate activation of glucose 6-phosphate dehydrogenase (G6PD) activity, the key enzyme in the PPP pathway. Changes in glycolysis due to diamide treatment were also determined by measurements of lactate production from D-[U-14C]-glucose. Production of lactate by the conceptus exposed to 250-500 microM diamide for 60 min was reduced (to approximately 54% of control values) concomitantly with a significant inhibition of the glycolytic enzymes, glyceraldehyde 3-phosphate dehydrogenase (GPD) and phosphofructokinase (PFK), indicating an overall decrease in glycolysis. Diamide was found to produce a differential effect on the enzymatic activities determined in this study, with greater degrees of inhibition seen in the tissue supernatants from the visceral yolk sac (VYS) compared to those from the embryo. Activities of GPD and PFK were decreased to approximately 22% and 43% control values, respectively, when determined in the supernatants from the VYS of the conceptus exposed to 500 microM diamide for 60 min. In addition, more than 90% of the GPD activity in the VYS, but not the embryo, was rapidly inhibited by the thiol alkylating agent N-ethylmaleimide (NEM, 100 microM) within 15 min of the exposure. In contrast to diamide and NEM, no alterations in lactate production were seen in the conceptus treated with the GSH depletor L-buthionine-S,R-sulfoximine (1 mM) for 5 hr in the culture media. Further experiments demonstrated that the activity of the GPD, inhibited by a 30-min incubation with 500 microM diamide, can be reversed after removal of diamide and that this effect was potentiated by subsequent treatment with dithiothreitol (30 mM), a thiol reducing agent. These results indicated the involvement of thiol/disulfide status in regulation of the metabolism of glucose in the developing conceptus and support the hypothesis that GSH oxidation and protein-S-SG formation could be a critical event associated with mechanisms of embryotoxicity elicited by oxidative stress. It was suggested in this study that, under these experimental conditions, embryotoxicity induced by diamide is primarily mediated via altered VYS functions, including disrupted energy production (glycolysis).
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PMID:Diamide-induced alterations of intracellular thiol status and the regulation of glucose metabolism in the developing rat conceptus in vitro. 883 90

The reactivities of the sulfhydryl groups of rat, turkey, human, and calf hemoglobin were studied together with the enzyme activities of glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutaredoxin in lysed erythrocytes to evaluate their roles in regulating redox homeostasis. The results of -SH reactivity showed rate constants spanning four orders of magnitude (k2, calf, 6.67 M-1 s-1; rat -SH fast reacting, 2.8 x 10(4) M-1 s-1). Enzyme activities of glucose-6-phosphate dehydrogenase ranged from 0.402 U/ml (calf) to 0.900 U/ml (rat), glutathione reductase from 0. 162 U/ml (rat) to 0.381 U/ml (human), glutaredoxin from 0.778 U/ml (rat) to 2.28 U/ml (turkey), and glutathione peroxidase from 2.07 U/ml (human) to 27.3 U/ml (rat). Blood samples of the four species were also treated with 0.5-1.5 mM tert-butyl hydroperoxide (t-BOOH) or diamide, and levels of glutathione-derived species [GSH, GSSG, and glutathione-protein mixed disulfides (GS-SP)] were determined within 120 min and related to the corresponding protein -SH group (PSH) reactivities and enzyme repertoires. In all cases t-BOOH rapidly transformed GSH into GSSG by the action of glutathione peroxidase; GSSG was in turn transformed into GS-SP, according to the reaction GSSG + PSH --> GS-SP + GSH, or reduced back to GSH by glutathione reductase. The GSSG reduction was more efficient in rat and human blood, due to the contribution of the fast-reacting -SH of hemoglobin, in the rat, and to the efficiency of the enzyme repertoire of human blood. Calf blood showed a relatively low capacity to restore normal values after oxidative stress, due to its low PSH reactivity and the weak contribution of its enzymes. Diamide treatment, which is known to react nonenzymatically with thiols, gave increased GS-SP levels in rat and turkey, but not in human and calf blood, as expected from the different corresponding PSH reactivities. Species with relatively high PSH reactivity and glucose 6-phosphate dehydrogenase activity, such as the rat, therefore had a higher antioxidant capacity than species (calf) in which these parameters were relatively low.
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PMID:Role of protein -SH groups in redox homeostasis--the erythrocyte as a model system. 967 20

Changes in the concentrations of protein-mixed disulfides (XS-SP) of glutathione (GSH), cysteine (CSH), and cysteinylglycine (CGSH) were studied in human platelets treated with diamide and t-BOOH in timecourse experiments (time range, 1-30 min) in order to understand the contribution of minor thiols CSH and CGSH to the regulation of glutathione-protein mixed disulfides (GS-SP). Diamide was much more potent than t-BOOH in altering the platelet thiol composition of XS-SP (threshold dose: diamide, 0.03 mM; t-BOOH, 0.5 mM) and caused reversible XS-SP peaks whose magnitude was related to the concentration of free thiols in untreated cells. Thus maximum levels of GS-SP (8 min after 0.4 mM diamide) were about 16-fold higher than those of controls (untreated platelets, GS-SP = 0.374 nmol/10(9) platelets), whereas those of CS-SP and CGS-SP were only 4-fold increased (untreated platelets, CS-SP = 0.112 nmol/10(9) platelets; CGS-SP = 0.024 nmol/10(9) platelets). The greater effects of diamide with respect to t-BOOH were explained on the basis of the activities of fast reactive protein SH groups for diamide and glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G-6-PDH) for t-BOOH. The addition of cysteine (0.3 mM, at 4 min) after treatment of platelets with 0.4 mM diamide increased the rate of reversal of GS-SP peaks to normal values, but also caused a relevant change in CGS-SP with respect to that of platelets treated with diamide alone. An increased gamma-glutamyltranspeptidase activity was found in platelets treated with diamide. Moreover, untreated platelets were found to release and hydrolyze GSH to CGSH and CSH. Ratios of thiols/disulfides (XSH/XSSX) and activities of GR and G-6PDH were also related to a high reducing potential exerted by GSH but not by minor thiols. The lower mass and charge of minor thiols is a likely requisite of the regulation of GS-SP levels in platelets.
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PMID:Minor thiols cysteine and cysteinylglycine regulate the competition between glutathione and protein SH groups in human platelets subjected to oxidative stress. 1090 Jan 26

Oxidative events involving band 3 (Anion Exchanger 1) have been associated with RBC (red blood cell) removal through binding of NAbs (naturally occurring antibodies); however, the underlying mechanism has been only partially characterized. In addition to inducing direct membrane protein oxidative modification, oxidative treatment specifically triggers the phosphorylation of band 3 tyrosine residues. The present study reports that diamide, a thiol group oxidant, induces disulfide cross-linking of poorly glycosylated band 3 and that the oligomerized band 3 fraction is selectively tyrosine phosphorylated both in G6PD (glucose-6-phosphate dehydrogenase)-deficient and control RBCs. This phenomenon is irreversible in G6PD-deficient RBCs, whereas it is temporarily limited in control RBCs. Diamide treatment caused p72 Syk phosphorylation and translocation to the membrane. Diamide also induced p72 Syk co-immunoprecipitation with aggregated band 3. Moreover, following size-exclusion separation of Triton X-100-extracted membrane proteins, Syk was found only in the high-molecular-mass fraction containing oligomerized/phosphorylated band 3. Src family inhibitors efficiently abrogated band 3 tyrosine phosphorylation, band 3 clustering and NAbs binding to the RBC surface, suggesting a causal relationship between these events. Experiments performed with the non-permeant cross-linker BS(3) (bis-sulfosuccinimidyl-suberate) showed that band 3 tyrosine phosphorylation enhances its capability to form large aggregates. The results of the present study suggest that selective tyrosine phosphorylation of oxidized band 3 by Syk may play a role in the recruitment of oxidized band 3 in large membrane aggregates that show a high affinity to NAbs, leading to RBC removal from the circulation.
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PMID:Oxidized and poorly glycosylated band 3 is selectively phosphorylated by Syk kinase to form large membrane clusters in normal and G6PD-deficient red blood cells. 1894 14

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