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Query: KEGG:D00031 (Glutathione)
 5,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione plays an important role in biology and medicine. Most cells of plants and animals contain high concentrations of reduced glutathione and a much smaller amount of oxidised glutathione. GSH is important for several metabolic functions of live cells, e.g. the protection of oxidative stress by peroxides, mediation of enzyme reactions, regulation of metabolic events, transport of amino acids across cell membranes via the gamma-glutamyl cycle, elimination of foreign compounds by GSH-conjugation, release of neurotransmitter substances. Irreversible perturbations of the glutathione metabolism may be the reason for severe clinical symptoms of hemolytic anemia or, perhaps, of central nervous disease.
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PMID:[Glutathione (author's transl)]. 0 May 43

Insulin and glucagon degradation by rat kidney homogenates and subcellular fractions was examined under a variety of conditions including high and low substrate concentrations, at pH 4 and pH 7, with and without glutathione. At high insulin concentration (4.1 - 10(-5) M) insulin degradation by the homogenate was greatest at pH 4 but at low insulin concentration (1 - 10(-10) M) insulin degradation was greatest at pH 7. At either high or low glucagon concentration glucagon degradation by the homogenate was greatest at pH 7. Glutathione at pH 7 stimulated insulin degradation at high insulin concentrations and inhibited insulin degradation at low concentrations; Glucagon degradation at pH 7 was inhibited at both high and low concentrations of glucagon by glutathionemseparation of kidney into cortex and medulla prior to homogenation produced a pattern of insulin and glucagon degradation identical to the whole homogenate but glucagon degradation by the medulla was greater than by the cortex. Examination of degradation by subcellular fractions revealed that at high concentration at neutral pH most insulin was degraded by the 100 000 X g pellet but at low insulin concentrations over 90% of the activity was in the 100 000 X g supernatant; At pH 7, at both high and low concentrations, most glucagon-degrading activity was in the 100 000 X g pellet, although the cytosol also had activity; At pH 4 most degradation occurred in the lysosomal fractions. Separation into cortex and medulla again showed similar distribution of activity as the whole gland with the medulla having more glucagon-degrading activity than the cortex. With low insulin concentrations the cortex 100 000 X g supernatant had higher relative specific activities than the medulla supernatant. Examination of recoveries of enzyme activity revealed that the subcellular fractions consistently had markedly less insulin-degrading activity than the original homogenate. This loss of activity was only discernible when insulin degradation was performed at pH 7 at low substrate concentrations. Comparable losses of glucagon-degrading activity were not seen.
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PMID:Insulin and glucagon degradation by the kidney. I. Subcellular distribution under different assay condition. 0 5

1. Equilibrium dialysis studies have been made of the binding of a number of small molecules by rat ligandin. Direct measurements of binding together with competition experiments indicated that bromosulphophthalein, oestrone sulphate and dehydroepiandrosterone sulphate each bind at the same single primary binding site with association constants of 1.1 X 10(7), 6.6 X 10(5) and 2.6 X 10(5) 1/mol respectively at pH 7.0,IO.16M,4 degrees C. As well as bromosulphophthalein and dehydroepiandrosterone sulphate, a number of strucurally similar organic anions including 2-hydroxyoestradiol-glutathione oestrone glycyronide, N-methyl-4-aminoazobenzene-glutathione and several bile acids, were able to displace oestrone sulphate from ligandin in a manner consistent with competition at a single binding site. From these experiments association constants for the competing ligands were derived; these were inthe range 1 X 10(4)-1 X 10(6) 1/mol. 2. Ligandin was found to bind a number of compounds for which, because of their low aqueous solubilities relative to their binding affinities complete binding isotherms could bot be obtained. These included several steroids (but not cortisol), 20-methylcholanthrene, diethylstilboestrol, oleate and palmitate. Oestrone sulphate was able to compete with these ligands for binding and the results of the competition experiments were interpretable in terms of 1:1 competition at a single binding site. 3. In general the conjugation of non-polar ligands with sulphate or glutathione resulted in increased affinities, but such increases were relatively small (approximately 15% in therms of free energy) implying that the main driving force for the binding of both the conjugated and unconjugated species was the hydrophobic effect. This conclusion is borne out by the observations that both oestrone and its sulphate showed slight increases in affinity with increase in ionic strength, as would be expected for hydrophobic interactions. 4. As well as non-polar compounds and organic anions, ligandin was also found to bind sulphate and glucuronate to a measurable degree, and to interact quite strongly with glutathione. For the latter compound a single binding site was found with an association constant of 1 X 10(5) 1/mol. Glutathione was able to cause the dissociation of the ligandin-oestrone sulphate complex, but this effect was not explicable in terms of simple 1:1 competition. 5. Both oestrone and oestrone sulphare were bound most strongly at pH 6-7, the affinity of the protein for these ligands falling off quite sharply on either side of this maximum. 6. The affinities of ligandin for bromosulphophthalein, steroids and their conjugates, diethylstilboestrol and N,N-dimethyl-4-aminoazobenzene are similar in magnitude to those of serum albumin and aminoazodye-binding protein A (B. Ketterer, E. Tipping, J.F. Hackney and D. Beale, 1976).
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PMID:The non-convalent binding of small molecules by ligandin. Interactions with steroids and their conjugates, fatty acids, bromosulphophthalein carcinogens, glutathione and realted compounds. 0 81

1. Leucine aminopeptidase does not catalyze the hydrolysis of glutathione. 2. Glutathione inhibits the hydrolysis of the substrates leucine hydrazide and leucine-p-nitroanilide by leucine aminopeptidase. 3. By means of kinetic experiments the type of the inhibition has been determined as noncompetitive. The inhibition constant Ki for the Mg2+-activated enzyme is five times higher than for the non-activated enzyme. 4. The degree of inhibition caused by glutathione depends on the pH value indicating a competition between glutathione and OH- ions. Mg2+-activated enzyme is invariably inhibited in the investigated pH range of 7.2 to 9.8. 5. A preincubation of the enzyme with glutathione changes the degree of activity enhancement by metal ions.
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PMID:[Influence of glutathione on the catalytic properties of leucine aminopeptidase]. 0 67

Glutathione depletion following inhalation of halogenated anesthetics was investigated as a possible mechanism of toxic reactions associated with anesthesia. Concentrations of reduced glutathione were measured in the blood, liver, lung and kidney of the mouse after anesthesia with enflurane, fluroxene, halothane, isoflurane, methoxyflurane, or trichloroethylene. The anesthetic had no effect on glutathione concentrations in tissues except when fluroxene was used. After two hours of fluroxene anesthesia, glutathione in liver, lung, kidney, and blood was depleted by 93, 85, 85, and 61 per cent, respectively. The depletion was dose-dependent and was more extensive in animals anesthetized after phenobarbital pretreatment. Glutathione was also depleted in livers and lungs of rats anesthetized with fluroxene (60 and 38 per cent, respectively). In blood of rhesus monkeys anesthetized with fluroxene, glutathione was depleted by only 13 per cent. Extents of glutathione depletion are related to fluroxene toxicities in the three species studied.
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PMID:Glutathione depletion following inhalation anesthesia. 2 82

Eight disulfides (I-VIII) and a thiolsulfonate (IX) were promising blocking agents of lymphocytes in graft-versus-host reactions (GvHR) without comensurate intracellular effects. The blocking effects were assayed through inhibition of the local GvHR after parental lymphocytes had been incubated with agents at suitable concentrations and then inoculated into F1 hybrid offspring. The intracellular effects were assessed beforehand by measuring the inhibition of [6-3H]thymidine incorporation by lymphocytes in the presence of a wide range of concentrations of agents. Concentration levels which induced no greater than approx. 50% inhibition of the [6-3H] thymidine incorporation were considered to reflect sufficiently small intracellular effects and were used for the subsequent GvHR comparisons. Cellular survival always was 90% or more for the GvHR tests (unless stated otherwise), even when inhibition of thymidine incorporation was as high as 50%; hence the thymidine data are useful not only as guides for dose levels in the GvHR but also as leads to new agents that may show immunosuppressive or anti-leukemic activity through intracellular effects. Structural specificity of the active compounds as cell-surface poisons is evidenced by little or no activity (less than 30% inhibition of GvHR) of 28 other disulfides, 2 trisulfides, 2 Bunte salts, and 8 other thiolsulfonates. Active agents may owe this function to replacement of the H of SH in cell-surface thiol receptors by an SR group. Glutathione did not significantly inactivate agents, probably because the products of reaction also are active disulfides. When two agents (III, IX) were given orally or intraperitoneally to F1 hybrid recipients of untreated parental cells, doses of 10--15 mg/kg produced a GvHR inhibition of 17--53%.
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PMID:Lymphocyte surface poisons: disulfides and thiolsulfonates. 3 May 42

6-Thiopurine when incubated in the presence of rat liver microsomes and reduced nicotine adenine dinucleotide phosphate (NADPH) binds to microsomal protein. Data support a mechanism involving initial metabolic activation via a cytochrome P450 mediated reaction to an intermediate which binds to protein. Glutathione protects against protein binding of the 6-thiopurine metabolite.
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PMID:Cytochrome P-450 dependent irreversible binding of 6-thiopurine to rat liver microsomal protein in vitro and protection by glutathione. 3 62

Glutathione and cysteine bind to the heme of lactoperoxidase, thereby causing a red shift of the Soret band which is reversed upon addition of iodide or guaiacol, two substrates for lactoperoxidase. The rate of formation of the enzyme-thiol complex is enhanced by diiodotyrosine. Binding of diiodotyrosine to lactoperoxidase does not cause a shift of the Soret band which indicates binding to the protein of the enzyme. At neutral pH and low ionic strength, lactoperoxidase is adsorbed on insolubilized diiodotyrosine (diiodotyrosine-agarose). It can be eluted at slightly increased ionic strength which shows that the binding is weak. In the presence of 5 X 10(-4) M glutathione, however, the binding of the enzyme to diiodotyrosine-agarose becomes much stronger so that a high salt concentration is required for elution. Lactoperoxidase is also adsorbed on insolubilized thiols (thiol-agarose). The presence of diiodotyrosine is not required for strong binding. A simple method for the preparation of lactoperoxidase from milk by affinity chromatography is based on the interactions of the enzyme with the two ligands, thiols and diiodotyrosine.
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PMID:Interaction of lactoperoxidase with thiols and diiodotyrosine. 3 12

Translocation of intracellular glutathione to the medium was studied in lymphoid cells (grown in tissue culture) that have very high, very low, or intermediate levels of membrane-bound gamma-glutamyl transpeptidase, in the absence and presence of various inhibitors of this enzyme. The data show that glutathione is translocated to the medium by all of the cell lines studied, but that glutathione does not accumulate in the medium unless the cellular transpeptidase activity is either very low or substantially inhibited. Translocation of glutathione does not seem to be directly related to the activity of gamma-glutamyl transpeptidase. The present and previous [Griffith, O.W. & Meister, A. (1979) Proc. Natl. Acad. Sci. USA 76, 268--272] findings suggest that translocation of intracellular glutathione is a general property of many mammalian cells. Glutathione exported from cells that have membrane-bound transpeptidase may be recovered by the cell in the form of transpeptidation or degradation products. Translocation of glutathione may also reflect operation of a rather general mechanism that protects and maintains the integrity of cell membranes.
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PMID:Translocation of glutathione from lymphoid cells that have markedly different gamma-glutamyl transpeptidase activities. 3 14

A chemically defined liquid medium has been developed for the study of the physiology and antigen production of the Legionnaires disease bacterium. The medium contains basal salts, vitamins, alpha-ketoglutaric acid, pyruvate, 0.05% l-cysteine, 0.05% glutathione, and a mixture of 20 additional amino acids, each of 0.01% final concentration, except serine, which was at 0.1%. The medium in shake culture at 37 degrees C with increased CO2 at pH 6.5, supports the maximum rate of growth, the highest cell yields, and the maximum cell surface antigen as distinguished by specific fluorescein isothiocyanate-conjugated antibody. Studies during the development of this medium showed that CO2, pyruvate, and alpha-ketoglutarate strongly stimulated growth; that cysteine and methionine were required for growth; and that serine, threonine, histidine, tyrosine, and tryptophane were energy sources. Glutathione substituted for cysteine, but cystine did not. The organisms did not use glucose and polysaccharides, as judged by cell yields when these carbohydrates were present or absent. The chelators malate, citrate, and ethylenediaminetetraacetic acid totally inhibited growth. Beta-mercaptoethanol, thioglycolate, dithiothreitol, and Tween 80 (0.05%) inhibited growth strongly or completely. Catalase activity was extremely weak or absent. Morphology varied, depending upon conditions and phases of growth. In general, filamentous forms became chains of cigar-shaped bacilli fragmenting to pairs and becoming coccoidal in the late stationary pha-e of growth. The organism grew at 25, 30, and 37 degrees C. Although they varied in their growth characteristics, 10 isolates were passed for five transfers in the chemically defined broth, giving maximum rates of growth, cell yields, and antigen production.
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PMID:Development of a chemically defined liquid medium for growth of Legionella pneumophila. 3 86


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