Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of T-2 toxin on liver lipid peroxidation, glutathione shuttle enzymes and microsomal reductases have been studied in rats at 8, 16 and 24 hr after feeding a single dose of toxin (2.0 mg/kg) and at 7, 14 and 21 days after feeding of toxin (0.75 mg/kg) daily. Feeding of a single dose of T-2 toxin caused significant increase in liver lipid peroxidation in rats at 8, 16 and 24 hr post treatment. The liver lipid peroxidation was also significantly increased at 14 and 21 days after feeding of 0.75 mg/kg of T-2 toxin daily to rats. The activities of liver GSH-shuttle enzymes, i.e. glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, were significantly higher in rats after both feeding schedules of T-2 toxin. NADPH-cytochrome c reductase activity was significantly lower at 8, 16 and 24 hr in liver of rats fed a single dose of T-2 toxin, whereas NADH-cytochrome b5 reductase was significantly higher until 16 hr and then declined below normal at 24 hr post treatment. In rats fed multiple doses of T-2 toxin, both liver microsomal reductases were significantly reduced. These results suggest that T-2 toxin/or its metabolites in the liver may be involved in the generation of free radicals which cause the observed increase in lipid peroxidation.
 ...
PMID:Effect of oral administration of T-2 toxin on glutathione shuttle enzymes, microsomal reductases and lipid peroxidation in rat liver. 279 41

Oxidation of diethyldithiocarbamate (DTC) to disulfiram (DS) by liver microsomes was tested in vitro by using a copper-DTC chelate formation reaction after the conversion of DS to DTC by glutathione (GSH). In the presence of NADPH, microsomes produced DS from DTC in both the free and microsome-bound forms, the former being greater than the latter. DS production was dependent on NADPH and DTC concentrations, and incubation time. Increases in microsomal concentrations, up to a certain level, also increased the free and total DS production. NADH was only somewhat effective, both the exposure to a nitrogen atmosphere and heat-denaturation of the microsomes suppressed the reaction. Preincubation of microsomes with both DTC and NADPH markedly decreased aniline hydroxylase, p-nitroanisole O-demethylase and glucose-6-phosphatase activities, and moderately decreased NADH-ferricyanide and NADH-cytochrome c reductase, but NADPH-cytochrome c reductase was minimally affected. DTC alone had only slight effects on the activities. DS also decreased these enzyme activities, particularly glucose-6-phosphatase; the loss of NADPH-cytochrome c reductase activity being protected in the presence of NADPH. GSH almost completely prevented the loss of microsomal enzyme activities induced by DTC and NADPH except for the drug metabolizing activities, in which protection was incomplete. The microsomal oxidation of DTC to DS could play a role in the action of DS in the liver, since DS is rapidly degradated to DTC in vivo.
 ...
PMID:Oxidation of diethyldithiocarbamate to disulfiram by liver microsomes in the presence of NADPH and subsequent loss of microsomal enzyme activity in vitro. 285 81

Transglutaminase activity in rat islet homogenates was increased after preincubation of the islets at high glucose concentration, and severely decreased after preincubation in the presence of either 1,2-bis(2-chloroethyl)-1-nitrosurea or 2-cyclohexene-1-one. The stimulatory action of glucose was still observed when the islets were preincubated in the absence or extracellular Ca2+. The enzymic activity was decreased by NAD+ or NADP+ but not NADH or NADPH, and inhibited by GSSG more than by GSH. These findings suggest that the glucose-induced activation of transglutaminase may be related to induction of a more reduced redox state with subsequent change in thiol-disulfide balance.
 ...
PMID:Glucose-induced activation of transglutaminase in pancreatic islets. 287 59

The major glutathione S-transferase isoenzyme from bovine brain was isolated and purified approx. 500-fold. The enzyme has a pI of 7.39 +/- 0.02 and consists of two non-identical subunits having apparent Mr values of 22,000 and 24,000. The enzyme is uniformly distributed in brain, and kinetic data at pH 6.5 with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate suggest a random rapid-equilibrium mechanism. The kinetics of inhibition by product, by GSH analogues and by NADH are consistent with the suggested mechanism and require inhibitor binding to several different enzyme forms. Long-chain fatty acids are excellent inhibitors of the enzyme, and values of 1nKi for hexanoic acid, octanoic acid, decanoic acid and lauric acid form a linear series when plotted as a function of alkyl chain length. A free-energy change of -1900 J/mol (-455 cal/mol) per CH2 unit is calculated for the contribution of hydrophobic binding energy to the inhibition constants. The turnover number of the purified enzyme dimer is approx. 3400/min. When compared with the second-order rate constant for the reaction between CDNB and GSH, the enzyme is providing a rate acceleration of about 1000-fold. The role of entropic contributions to this small rate acceleration is discussed.
 ...
PMID:Purification and kinetic mechanism of the major glutathione S-transferase from bovine brain. 293 Apr 65

The reactivities of myeloperoxidase-H2O2-Cl- and sodium hypochlorite with amino acids, uric acid, NADH, ascorbic acid, ADP, albumin, haemoglobin, alpha 1-antitrypsin and some hydroxyl radical scavengers have been compared. The ability of each compound to inhibit chlorination of monochlorodimedon by both oxidants was measured. Relative reaction rates varied over a range of 10(5), but the reactivities of the two oxidants with each compound were very similar, from which it is concluded that the reactions of hypochlorite accurately reflect those of the myeloperoxidase system. Thiol compounds (cysteine and GSH) and methionine were more than 100-times more reactive than other amino acids, which had comparable reactivity to NADH and uric acid. Benzoate, dimethylsulphoxide and formate were very much less reactive. The significance of these reactions of myeloperoxidase in microbial killing and inflammation is discussed.
 ...
PMID:Comparative reactivities of various biological compounds with myeloperoxidase-hydrogen peroxide-chloride, and similarity of the oxidant to hypochlorite. 298 13

Peroxidase catalysed the formation of active oxygen in the presence of NADH or GSH and traces of H2O2 and arylamine or phenolic substrates. Some oxygen activation occurred with some arylamines even in the absence of NADH or GSH. Oxygen consumption was proportional to the NADH oxidized or GSSG formed. Approximately 0.80 and 0.40 mol of oxygen were consumed per mole of NADH or GSH oxidized respectively. The requirement for trace amounts of hydrogen peroxide and arylamine or phenolic substrates suggest that redox cycling resulted in H2O2 formation. It is proposed that initially formed phenoxy radicals or arylamine cation radicals oxidize NADH or GSH to radicals which react with oxygen to form superoxide radicals and H2O2.
 ...
PMID:Peroxidase catalysed oxygen activation by arylamine carcinogens and phenol. 300 Jun 37

Murexide underwent reduction by rat liver cytosolic fraction or a hypoxanthine-xanthine oxidase system to produce a free radical metabolite. Reduction of murexide by the freshly prepared cytosolic fraction depended upon the presence of ascorbic acid. N1-Methylnicotinamide, xanthine or hypoxanthine, in that order, could also serve as a source of reducing equivalents for the production of that free radical by the cytosolic fraction. Several thiol compounds (GSH, cysteine, and cysteamine), pyridine nucleotides (NADH, NADPH) and ascorbic acid were also effective in generating the murexide-derived free radical. Tetramethyl murexide was also reduced to its free radical derivative by a hypoxanthine-xanthine oxidase system.
 ...
PMID:Reduction of the metallochromic indicators murexide and tetramethylmurexide to their free radical metabolites by cytoplasmic enzymes and reducing agents. 300 49

Single or sequential treatment of rats with the thiol N-acetyl-L-cysteine (NAC), the glutathione depletor diethyl maleate (DEM) and the enzyme inducer Aroclor 1254 (AR) produced several significant variations on metabolic activities of pulmonary alveolar macrophages (PAM). Specifically, all three compounds elicited an increase in some oxidoreductase activities, including the two dehydrogenases involved in the hexose monophosphate shunt (G6PD and 6PGD) and NADH- or NADPH-dependent diaphorases. Diaphorase activities were especially increased by sequential treatments with AR and DEM or with DEM and NAC. Both NAC and AR also stimulated other detoxifying mechanisms, such as those related to GSH S-transferase activity and to the NADPH-dependent reduction of hexavalent chromium. Therefore, all the monitored parameters were significantly enhanced not only by the enzyme inducer, but also by the thiol, demonstrating its protective role in the biotransformation of mutagenic/carcinogenic compounds.
 ...
PMID:Detoxifying activities in alveolar macrophages of rats treated with acetylcysteine, diethyl maleate and/or aroclor. 309 27

The purified glutathione reductase was homogeneous on polyacrylamide-gel electrophoresis. It had an Mr of 79,000 and consisted of two subunits with a Mr of 40,000. The activity was maximum at pH 8.2 and 52 degrees C. It was specific for NADPH but not for NADH as the electron donor; the reverse reaction was not observed. The Km values for NADPH and GSSG were 14 and 55 microM respectively. The enzyme activity was markedly inhibited by thiol inhibitors and metal ions such as Hg2+, Cu2+ and Zn2+. Euglena cells contained total glutathione at millimolar concentration. GSH constituted more than 80% of total glutathione in Euglena under various growth conditions. Glutathione reductase was located solely in cytosol, as were L-ascorbate peroxidase and dehydroascorbate reductase, which constitute the oxidation-reduction cycle of L-ascorbate [Shigeoka et al. (1980) Biochem. J. 186, 377-380]. These results indicate that glutathione reductase functions to maintain glutathione in the reduced form and to accelerate the oxidation-reduction of L-ascorbate, which scavenges peroxides generated in Euglena cells.
 ...
PMID:Characterization and physiological function of glutathione reductase in Euglena gracilis z. 310 93

The stabilities of several drug oxidation and conjugation pathways in human adult hepatocytes have been investigated during 72 hr culture. Cytochrome P-450-dependent mixed function oxidase was measured by the O-dealkylations of ethoxyresorufin (EROD), pentoxyresorufin (PROD) and benzyloxyresorufin (BROD), which are probes for different isozymes of cytochrome P-450 in the rat. EROD declined to 64% of initial fresh cell values after 72 hr in culture, whereas PROD increased to 162% and BROD remained relatively constant. Addition of phenobarbitone to the culture medium selectively increased PROD to a greater extent than EROD and did not affect BROD. NADPH-cytochrome c reductase and NADH-cytochrome b5 reductase were markedly labile during culture, declining to 32% and 22% of fresh cell values respectively. Epoxide hydrolase (EH) showed a large transient increase (2-5-fold) in enzyme activity 24 hr after culture, declining to fresh cell values by 48 hr. UDP-glucuronyltransferase (GT) activity towards phenolphthalein and 1-naphthol also increased (2-3-fold) during the 72 hr of culture, the greater and more rapid increase being observed with phenolphthalein glucuronidation. Sulphotransferase activity declined rapidly within 24 hr of culture, whereas reduced glutathione (GSH) levels and GSH conjugation were maintained at fresh cell values for 72 hr.
 ...
PMID:Human adult hepatocytes in primary monolayer culture. Maintenance of mixed function oxidase and conjugation pathways of drug metabolism. 311 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>