Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.2.3 (glutathione synthetase)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two brothers, aged 16 and 11 years, had recurrent episodes of vomiting, diarrhoea and abdominal pain, starting in infancy. In spite of extensive investigations no cause of their enterocolitis could be established. After several years symptomatic treatment was discontinued without any recurrence of symptoms. Their father and several paternal relatives have had kidney stones. Both boys developed urolithiasis and an oxalate-containing stone was removed from the elder brother's kidney. He had no hypercalciuria. His glomerular and tubular function tests were normal. Gas chromatography of urine from both brothers revealed massive excretion of L-5-oxoproline (pyroglutamic acid). Glutathione levels in erythrocytes of both patients were normal. The activities of enzymes of the gamma-glutamyl cycle were analysed in erythrocytes, leukocytes and cultured skin fibroblasts. The level of glutathione synthetase was normal, as was the affinity of this enzyme for its substrate gamma-glutamyl-cysteine. Feedback inhibition of gamma-glutamyl-cysteine synthetase by glutathione was also normal. Both patients had a specific deficiency of 5-oxoprolinase, the activity of which was 2-4% of that of control subjects. Their parents had intermediate 5-oxoprolinase activities in fibroblasts, indicating a recessive mode of inheritance. Thus, 5-oxoprolinuria in these two patients was due to a lack of 5-oxoprolinase, i.e., a new inborn error in the gamma-glutamyl cycle.
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PMID:5-oxoprolinuria due to hereditary 5-oxoprolinase deficiency in two brothers--a new inborn error of the gamma-glutamyl cycle. 611 26

Pure fetal blood was obtained by direct-vision fetoscopy from 66 fetuses at 17-24 weeks gestation. The concentration of GSH and the activities of the enzymes gamma-glutamylcysteine synthetase (GCS), glutathione synthetase (GS), glutathione reductase (GR) and glutathione peroxidase (GPx) were analysed by established techniques to find the normal ranges for this gestational age. The ranges were relatively narrow and could serve as reference values for the prenatal diagnosis of defects in the GSH metabolism of erythrocytes. The results were compared with those obtained from 38 normal adults and with published values on neonatal blood. In the case of GR a comparison was also made with maternal blood. In comparison with adults, fetal erythrocytes showed higher GSH concentration and GCS activity and lower GS and GPx activities. This pattern resembled that found in neonatal erythrocytes except for the GCS activity, which was higher in the fetal cells. Furthermore the differences between fetal and adult erythrocytes were more pronounced than those between neonatal and adult cells. The GR activity of fetal erythrocytes was also higher than that of either normal adult or maternal blood. This difference, however, was reduced to an insignificant level when the enzyme was activated in vitro by flavin adenine dinucleotide (FAD) because of a relatively low per cent activation of the GR in the fetal erythrocytes.
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PMID:Normal glutathione content and some related enzyme activities in the fetal erythrocytes. 614 50

Glutathione is not effectively transported into human lymphoid cells, normal human skin fibroblasts, and fibroblasts from patients with genetic deficiencies of gamma-glutamylcysteine synthetase or glutathione synthetase. On the other hand, the monoethyl ester of glutathione, in which the carboxyl group of the glycine residue is esterified, is readily transported into these cells and is hydrolyzed intracellularly. This leads to greatly increased cellular levels of glutathione, which often exceed those found normally. Glutathione ester was found to protect human lymphoid cells of the CEM line against the lethal effects of irradiation. Under the conditions employed, complete protection was found when the ester was added prior to irradiation. Addition of the ester after irradiation was partially effective, suggesting that GSH may also function in repair processes.
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PMID:Radioprotection by glutathione ester: transport of glutathione ester into human lymphoid cells and fibroblasts. 614 78

The enzymatic production of glutathione (GSH) has been studied in a bioreactor system using toluene-treated cells of Escherichia coli B transformed with recombinant plasmids for gamma-glutamylcysteine synthetase (GSH-I) and glutathione synthetase (GSH-II). As reported previously the genes for both enzymes were separately cloned onto vector plasmid pBR322. The plasmid for GSH-I was designated pGS100-2 and that for GSH-II as pGS200. The effect on GSH production in the bioreactor system, containing an ATP regenerating system, of using cells containing various hybrid plasmids has now been explored. Three kinds of hybrid plasmids, designated pGS300, pGS400, and pGS500, were constructed by subcloning the genes in pGS100-2 and pGS200 onto vector plasmid pBR325. pGS300 contained the E. coli B chromosomal DNA fragment with a gene for GSH-I in the PstI site of pBR325. pGS400 also contained E. coli B chromosomal DNA fragment with a gene for GSH-II in the HindIII site of pBR325. In contrast, pGS500 contained two kinds of DNA fragments with the genes for GSH-I and GSH-II in the PstI and HindIII sites of pBR325, respectively. All the hybrid plasmids thus prepared were stably maintained in E. coli cells when chloramphenicol was included at 10 micrograms/ml in the medium. The activity of the cells containing pGS300 was higher than that of the cells containing pGS400, although the former activity did not come up to that of cells having both pGS300 and pGS400. The highest glutathione-producing activity was found in the case of the cells transformed with pGS500 carrying both genes for GSH-I and GSH-II on the vector plasmid pBR325. About 5 mg/ml of glutathione was produced by E. coli cells with pGS500 from 80 mM L-glutamate, 20 mM L-cysteine, and 20 mM glycine within 3 h at 37 degrees C.
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PMID:Construction of glutathione-producing strains of Escherichia coli B by recombinant DNA techniques. 614 39

Using a human cell strain deficient in glutathione synthetase and a related control, the role of glutathione in repair mechanisms has been investigated. UV light has been used in order to avoid the interaction between thiols and free radicals. When potentially lethal damage repair is completed, deficient cells in plateau phase exhibit smaller surviving fractions than do control cells. The ratio of surviving fractions in control/deficient cells is about 2 for the same radiation dose. These results indicate that thiols and especially GSH are involved in repair mechanisms.
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PMID:Reduced PLD repair ability in glutathione synthetase deficient human fibroblasts after UV irradiation. 633 50

Glutathione synthetase was purified about 60-fold with 8.5% of activity yield from the cell extracts of Escherichia coli C600 cells transformed with a recombinant plasmid for the glutathione synthetase gene of E. coli B. The purified enzyme had a Mr of 152,000 and was composed of four identical subunits each with a Mr of 38,000. The Km values of the enzyme for gamma-glutamylcysteine, glycine, and ATP were 2.6, 2.0, and 1.8 mM, respectively. The enzyme was most active at pH 8.5 and at 45 degrees C and required divalent cations such as Mg2+, Mn2+, and Co2+ for activity. The activity was inhibited by oxidized glutathione (Ki = 4.4 mM). Reduced glutathione showed no effect on glutathione synthetase activity.
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PMID:Purification and characterization of glutathione synthetase from Escherichia coli B. 638 79

The nucleotide sequence of the cloned DNA, 1,478 bp in length coding for glutathione synthetase (GSH-II) of E. coli B has been determined. Amino acid and nucleotide sequence analyses have assigned the open reading frame for GSH-II, starting with the ATG near its 5' terminus. The molecular weight calculated from the predicted amino acid sequence is 35,559 daltons, being in good agreement with that of a GSH-II subunit estimated by the SDS-PAGE method. Several signal sequences conserved in the promoter regions of E. coli were found in the non-coding regions of the gsh-II gene. They include the Shine-Dalgarno sequence, the Pribnow box and the sequence conserved in the "-35 region" with a preferable spacing from each other for an efficient transcription. Downstream from the termination codon, the inverted repeat sequences were present, followed by 6 successive T's. These structural features found in the non-coding regions have suggested to be involved in regulatory functions for the gsh-II gene expression.
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PMID:Complete nucleotide sequence of the E. coli glutathione synthetase gsh-II. 639 55

A male newborn infant presented with metabolic acidosis and haemolytic anaemia. Renal tubular acidosis was suspected in the absence of amino aciduria and the patient was treated with sodium bicarbonate. Two years later, the chronic acidosis, clinical observation of developmental delay and ataxia prompted further investigational studies. 5-Oxoprolinuria was identified by gas-liquid chromatography and confirmed by mass spectrometry after an initial mass spectrum analysis reported a glutamic acid artifact. Glutathione and glutathione synthetase in erythrocytes were 25% and 5% of control values, respectively. On the basis of neonatal metabolic acidosis, without amino aciduria and an elevated reticulocyte count, a recommendation is made for blood glutathione and urine 5-oxoproline screening, followed by glutathione synthetase assay for confirmation of neonatal 5-oxoprolinuria.
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PMID:Neonatal 5-oxoprolinuria: difficult-to-diagnose? 640 9

The yield and rejoining of single-strand DNA breaks (ssb) was investigated after irradiation of cells which were deficient in glutathione (GSH) either due to a genetic defect of their GSH synthetase activity, or inhibition of gamma-glutamylcysteine synthetase activity by DL-buthionine-SR-sulfoximine (BSO). The results were concordant in indicating that decreased cellular GSH content is associated with an increased yield of ssb after anoxic, but not after aerobic radiation exposures. Rejoining of ssb was delayed and incomplete during a one hour's incubation period after oxic, but not after anoxic exposure of GSH-deficient cells. The defective rejoining capacity of these cells was restituted to nearly normal by the admixture of GSH-proficient cells in the incubation medium.
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PMID:Glutathione-dependent yield and repair of single-strand DNA breaks in irradiated cells. 642 3

Many studies have established the role of the glutathione S-transferases (GSTs) and glutathione (GSH) in the neoplastic process and the drug resistance of tumor. Using isoelectric focusing we separated different forms of GSTs in 28 renal cell carcinomas (RCCs) and in morphologically unchanged adjacent kidney. In addition we determined in RCCs and adjacent kidney the level of GSH and the activities of enzymes participating in synthesis and uptake of this thiol compound. We found higher activity of acidic GSTs and higher level of GSH in RCCs versus kidney. Therefore we suggest that both parameters may play the significant role in the well known phenomenon of intrinsic cytostatic drug resistance of RCC. We also observed the elevation of GSH synthetase activity in tumor tissues in comparison to the kidneys. It may indicate that GSH synthetase, catalysing the final step in GSH synthesis, may participate in the elevation of GSH concentration in RCCs. In this work we also compared the tested parameters in RCCs in relation to the size and local extent of primary tumor (T). We found significantly lower activity of gamma-glutamyl transpeptidase (GGT) as well as GSH synthetase in the group of T3 and T4 tumors than in T2 tumors. However, no substantial differences in GSH concentrations were observed between these distinguished groups.
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PMID:Glutathione S-transferase isoenzymes and glutathione in renal cell carcinoma and kidney tissue. 765 81


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