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)

This investigation examined many parameters during the course of early development of naphthalene-induced cataract in a time span of 0 to 79 days of treatment. Feeding naphthalene daily to Black-Hooded rats resulted in gradual progressive development of cataract. The first faint opacities were detectable after 7 days. Free soluble total glutathione (oxidized and reduced) of these lenses was shown to gradually decrease to a maximum loss of about 20%, a value reached by day 30 of treatment. No activity loss of either enzyme required for glutathione synthesis (gamma-glutamylcysteine synthetase or glutathione synthetase) was observed in homogenates of naphthalene versus control lenses. There was also neither impairment of [35S]-L-cystine uptake nor of [35S]-glutathione synthetic capacity in lenses cultured from rats after 12, 24 or 36 days of naphthalene feeding when compared to control lenses. Hence, glutathione loss cannot be explained by a damaged glutathione synthesis system. Progressive activity loss of glutathione peroxidase and glutathione reductase was observed. The loss of glutathione peroxidase activity was especially remarkable. Thus, the defense system against oxidative damage is impaired and may be a significant factor in naphthalene-induced cataract of the rat.
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PMID:Glutathione synthesis and glutathione redox pathways in naphthalene cataract of the rat. 196 27

A number of enzyme systems are important in the protection of cells from chemical-induced oxidative damage. Little is known of the relative importance of these enzymes during postnatal development and its is possible that changes in their activity during this period may alter the susceptibility to toxic agents. This study investigated the activities of glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase, gamma-glutamyl-cysteine synthetase and glutathione synthetase in the liver, lung and kidney of postnatal and adult mice. The first 3 postnatal weeks are characterized by marked changes in the activities of enzymes that protect against oxidative stress (glutathione peroxidase/reductase, catalase and superoxide dismutase). Overall, the activity of these enzymes suggests that the mouse has a higher level of protection against peroxides at various stages during this period but lower capacity to detoxify superoxide anions. The activities of the glutathione-synthetic enzymes (gamma-glutamylcysteine synthetase and glutathione synthetase) were significantly lower in the kidney of the postnatal mice, but the liver and lung had levels similar to those in the adult. Glutathione turnover in the liver of 2-week-old mice was not different from that in adults. The results indicate a complex pattern of development in the activities of detoxification enzyme systems during postnatal development.
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PMID:Postnatal development of enzyme activities associated with protection against oxidative stress in the mouse. 196 50

A strain of Escherichia coli, enriched in its content of gamma-glutamylcysteine synthetase and glutathione synthetase activities by recombinant DNA techniques, is more resistant to the lethal effects of gamma-irradiation than is the corresponding wild strain. Although the gene-enriched strain has higher glutathione levels than the wild strain, the observed radioresistance appears to be associated with the increased capacity of the gene-enriched strain to synthesize glutathione when irradiated rather than to the cellular levels of glutathione per se. Thus, resistance was abolished in the presence of buthionine sulfoximine, a selective inactivator of gamma-glutamylcysteine synthetase that decreases glutathione synthesis but that does not act directly to lower cellular glutathione levels. Conclusions drawn from studies on this E. coli model system may have relevance to protection of mammalian cells by glutathione.
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PMID:Increased capacity for glutathione synthesis enhances resistance to radiation in Escherichia coli: a possible model for mammalian cell protection. 256 2

The metabolism of glutathione and activities of its related enzymes were studied in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM). A decrease in the levels of the reduced form of glutathione and an increase in the levels of glutathione disulfide were found in erythrocytes of diabetics. To elucidate these changes in the levels of glutathione, synthetic and degradative processes were studied. The activity of gamma-glutamylcysteine synthetase was significantly lower in diabetics than in normal controls. The activity of glutathione synthetase of each group was the same. The rate of outward transport of glutathione disulfide in diabetics decreased to approximately 70% of that of normal controls. The activity of glutathione reductase decreased in diabetics. These data suggest that the decrease in the levels of reduced form of glutathione in erythrocytes of diabetics is brought about by impaired glutathione synthesis and that the increase in the levels of glutathione disulfide is brought about by the decreased transport activity of glutathione disulfide through the erythrocyte membrane together with a decrease in the activity of glutathione reductase. These data also suggest that the impairment of glutathione metabolism weakens the defense mechanism against oxidative stress in erythrocytes of diabetics.
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PMID:Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. 256 61

Sertoli cells play a major role in the regulation of spermatogenic cell energy metabolism and differentiation. This study demonstrates that Sertoli cells are essential for the maintenance of spermatogenic cell glutathione (GSH), an important intracellular reductant and detoxicant. Primary spermatocytes and round spermatids isolated from Xenopus laevis contained 1.5 +/- 0.1 mM GSH, but sperm lacked detectable GSH. During a 5-day culture period, isolated spermatocytes and spermatids lost 80% of the initial GSH (t 1/2 = 55 h). The levels of GSH were unaffected by L-buthionine-SR-sulfoximine (BSO), a selective inhibitor of GSH synthesis. Cultures of testicular lobules and spermatocysts (composed of germ cells and Sertoli cells) depleted of interstitial tissue lost only 30% of their initial GSH in 4.5 days; the GSH levels decreased during treatment with BSO. Spermatogenic cells in cultured testes maintained their GSH levels for 7 days by a BSO-sensitive mechanism. These results demonstrate that the intracellular GSH levels of spermatogenic cells are dependent upon germ cell-somatic cell interactions. Spermatogenic cells were shown to possess gamma-glutamyl transpeptidase, glutathione synthetase, 5-oxoprolinase, and gamma-glutamylcysteine synthetase activities. [35S] Cysteine incorporation and distribution as analyzed by high performance liquid chromatography (HPLC) showed that isolated spermatogenic cells are capable of GSH synthesis. The rate of GSH synthesis, however, was insufficient to compensate for GSH turnover. These results demonstrate that production of spermatogenic cell GSH is dependent upon Sertoli cells. To our knowledge, this is the first evidence that interactions between different cell types may be of significance in GSH metabolism.
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PMID:Spermatogenic cell-somatic cell interactions are required for maintenance of spermatogenic cell glutathione. 272 29

A procedure for synthesis of glutathione selectivity labeled with isotopes is described. A strain of Escherichia coli enriched in its content of gamma-glutamylcysteine synthetase and glutathione synthetase by recombinant DNA techniques is immobilized in a carrageenan matrix and treated with toluene to render the cells more permeable to the substrates. The immobilized cell matrix is incubated with a mixture containing the appropriately labeled amino acid, the other amino acid constituents of glutathione, ATP, and acetylphosphate. The radiolabeled product is isolated by column chromatography.
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PMID:Glutathione specifically labeled with isotopes. 286 14

The low activity level of lenticular gamma-glutamylcysteine synthetase appears to be an evolutionary phenomenon restricted to higher primates. Rapid reduction with age of the activity of both enzymes (gamma-glutamylcysteine synthetase and glutathione synthetase) required for glutathione synthesis in the human lens was demonstrated in an earlier study. The activities of gamma-glutamylcysteine synthetase and glutathione synthetase, the two enzymes responsible for glutathione synthesis, were determined in 39 lenses from the rhesus monkey (Macaca mulatta) as a function of age. The ages ranged from 137 day old fetuses to a 34 year old monkey. Glutathione synthetase activity decreased 8-fold (units/g lens), 7-fold (units/mg soluble protein) and 2-fold (units/lens) over the age span studied. gamma-Glutamylcysteine synthetase activity decreased 3-fold (units/g lens), 4-fold (units/mg soluble protein) and less than 2-fold (units/lens) over the same age span. A small increase in gamma-glutamylcysteine synthetase activity (units/lens) from embryonic lenses to birth and one year of age was followed in later years by a decrease in activity. In adults, the overall ratio of glutathione synthetase activity to gamma-glutamylcysteine synthetase activity was 42:1 as compared to 77:1 for the human and 2:1 to 4:1 for common domestic species. The aging study data indicate that the rhesus monkey lenticular glutathione synthesis system appears to be a good model for the human lens enzymic system.
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PMID:Activity of glutathione synthesis enzymes in the rhesus monkey lens related to age: a model for the human lens. 286 16

The activities of five enzymes of glutathione metabolism were determined in lenses from cataract-resistant and cataract-prone (Emory) mouse variants at three different ages (5 weeks, 10 weeks and 6 months). The enzymes included those required for glutathione synthesis, gamma-glutamylcysteine synthetase and glutathione synthetase, as well as glutathione-S-transferase, glutathione peroxidase and glutathione reductase. The differences in the activities of the five enzymes in the two mouse variants were not remarkable at any of the three ages. Activity of each enzyme was noted to be in excess of the preceding one in this integrated metabolic pathway, with the exception of glutathione reductase. gamma-Glutamylcysteine synthetase appears to be the pacesetting enzyme of this metabolic scheme in the mouse lens. The activity of each enzyme was compared with that earlier reported for human, rabbit and dog lenses.
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PMID:Glutathione metabolism in lenses of Emory and cataract-resistant mice: activity of five enzymes. 287 Aug 75

New methods for the estimation of red cell gamma-glutamylcysteine synthetase and glutathione synthetase have been developed. gamma-32P ATP is allowed to equilibrate until the gamma and beta phosphate groups are equally labelled. The amount of 32Pi released in the presence of glutamic acid and cysteine, the substrates for GC-S or in the presence of gamma-glutamylcysteine and glycine, the substrates of GSH-S, is measured. This is accomplished by extraction of the phosphomolybdate complex into isobutanol-benzene. The methods are linear with time and hemolysate concentration. Normal values are presented.
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PMID:Improved assay of the enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase and glutathione synthetase. 287 3

We report a new convenient assay of the activity of gamma-glutamylcysteine synthetase (EC 6.3.2.2) and glutathione synthetase (EC 6.3.2.3) in crude microbial extracts as well as in purified enzyme preparations. The assay is based on the quantitative analysis of the reaction products by high-performance liquid chromatography after derivatization of the thiol group with 5,5'-dithiobis-(2-nitrobenzoic acid) as described by J. Reeve, J. Kuhlenkamp, and N. Kaplowitz [(1980) J. Chromatogr. 194, 424-428]. In addition, the procedure yields information on basal levels of gamma-glutamylcysteine and glutathione in crude microbial extracts. The two enzymes responsible for glutathione biosynthesis can be determined in parallel under the same chromatographic conditions. No prior separation from substrates and by-products is necessary. Product formation is linear with time for at least 30 min between 0.03 and 12 mU for both enzymes. Even in crude extracts 0.2-0.5 nmol of products formed can be detected with certainty. The method was found to be sensitive and highly reproducible.
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PMID:Assay of the glutathione-synthesizing enzymes by high-performance liquid chromatography. 287 17


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