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)

Spectrophotometric assay methods are described for glutathione synthetase, gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase of erythrocytes. The contents of these enzymes in normal human erythrocytes are reported. Erythrocyte glutathione synthetase is inhibited by ADP; this inhibition is competitive with respect to ATP. gamma-Glutamylcysteine synthetase is subject to feedback inhibition by GSH, and is also inhibited by NADH, and to a lesser extent by NAD(+) and NADPH. This enzyme is irreversibly inactivated by cysteamine.
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PMID:Studies in the enzymology of glutathione metabolism in human erythrocytes. 438 10

1. An improved radioassay for glutathione synthetase and gamma-glutamylcysteine synthetase was developed. 2. Xenopus laevis liver gamma-glutamylcysteine synthetase was purified 324-fold by saline-bicarbonate extraction, protamine sulphate precipitation, CM-cellulose and DEAE-cellulose column chromatography, and gel filtration. 3. Rat liver gamma-glutamylcysteine synthetase was purified 11400-fold by a procedure similar to that employed for the Xenopus laevis enzyme. 4. Rat liver gamma-glutamylcysteine synthetase activity was inhibited by GSH and activated by glycine. These effects, which were not found in the enzyme from Xenopus laevis, may have a regulatory significance. 5. Isotope-exchange experiments revealed fundamental differences in the partial reactions catalysed by the rat and Xenopus laevis synthetases. The enzyme from Xenopus laevis appears to follow a Bi Bi Uni Uni Ping Pong mechanism, with glutamyl-enzyme as intermediate before the addition of cysteine and the release of gamma-glutamylcysteine. The results for the rat liver enzyme are consistent with a Tri Tri sequential mechanism.
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PMID:Assay, purification, properties and mechanism of action of gamma-glutamylcysteine synthetase from the liver of the rat and Xenopus laevis. 474 28

Evidence is presented that rat kidney contains enzymes that catalyze the synthesis and utilization of glutathione; these reactions, which involve the uptake and release of amino acids from gamma-glutamyl linkage, constitute a cyclical process which is termed "the gamma-glutamyl cycle." The gamma-glutamyl cycle has properties that fulfill the requirements of an amino acid transport system. Thus, gamma-glutamyl transpeptidase may function in translocation and gamma-glutamylcysteine synthetase and glutathione synthetase may catalyze energy-requiring "recovery" steps in transport. These and other considerations suggest that glutathione serves a carrier function in amino acid transport.
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PMID:The gamma-glutamyl cycle: a possible transport system for amino acids. 527 54

Human fetal and adult liver were found to have similar concentrations of acid soluble sulfhydryl (SH) groups (7.4 mmol/kg) in the same range as is found in adult mouse and rat liver. The concentration was 4-fold higher than in human fetal adrenal gland tissue. Methods specific for glutathione (GSH) associated SH groups revealed that the postmortem levels of GSH is very low (0.4 mmol/kg) in relation to total SH groups. In contrast, the levels of cysteine were high (2.8 mmol/kg), indicating a rapid cleavage of GSH. Only negligible amounts of gamma-glutamylcysteine and cysteinylglycine were measured. Our findings may be explained by high fetal activity of gamma-glutamyl transpeptidase (which metabolizes GSH) that has been documented previously both in man and in experimental animals. High activities of the two GSH-synthesizing enzymes, gamma-glutamylcysteine synthetase and GSH synthetase were found in the human fetal liver (7.1 and 3.0 mukat/kg, respectively). The activities of these enzymes were in the same range as in human adult liver, whereas that of gamma-glutamyl transpeptidase was 3-fold higher in the fetal liver. Our results demonstrate the presence of high concentration of SH groups and capacity to synthesize GSH already in the first and second trimester of the human fetal gestation. This has more than theoretical interest, since we assume that the SH groups (GSH) have importance for the protection of the fetus against drugs and foreign compounds and their (toxic) metabolites, the formation of which is catalyzed by the fetus itself.
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PMID:Glutathione and gamma-glutamyl cycle enzymes in human fetal liver. 611 63

Mutants of Escherichia coli B that contain essentially no detectable glutathione were isolated. These mutants had a very low activity of gamma-glutamylcysteine synthetase or glutathione synthetase. No significant differences in growth in minimal medium were observed between the mutants and the parental strain. The mutants lacking gamma-glutamylcysteine synthetase activity were more susceptible to toxic compounds than either the parental strain or a glutathione synthetase-deficient strain. The mutants lacking gamma-glutamylcysteine synthetase activity were also susceptible to oxygen.
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PMID:Some properties of glutathione biosynthesis-deficient mutants of Escherichia coli B. 612 59

Several biochemical parameters were examined in clear dog and rabbit lenses as functions of age, and in posterior subcapsular cataracts in the Alaskan malamute. Tabulated data include soluble protein, reduced sulfhydryl content of soluble protein, reduced glutathione, water, and activity of five enzymes of glutathione metabolism. The enzymes include the glutathione biosynthesis system consisting of gamma-glutamylcysteine synthetase and glutathione synthetase, as well as glutathione peroxidase, glutathione reductase and glutathione-S-transferase. Each enzyme, acting last in a sequential reaction of either two or three reactions, was in excess activity over the preceding enzyme(s) in every case but one. In the exception, the ratio of glutathione reductase to glutathione peroxidase activity was about 1:600 and 1:155 in the dog and rabbit lens, respectively.
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PMID:Glutathione metabolism in lenses of dogs and rabbits: activities of five enzymes. 613 32

The high levels of both enzymes of glutathione synthesis found in the infant human lens rapidly reached lower levels by age 10, and thereafter the rate of decrease diminished. Glutathione synthetase activity in the 6 month old lens was six-fold (units/g lens), four-fold (units/mg soluble protein) and two-fold (units/lens) higher than that in the 83 year old, clear human lens. gamma-Glutamylcysteine synthetase activity in the 6 month old lens was sixteen-fold (units/g lens), ten-fold (units/mg soluble protein) and six-fold (units/lens) higher than that in the 83 year old, clear human lens. When lenses from the young adult beagle, rabbit, bovine, and humans are compared, glutathione synthetase activity (units/g lens) varies by about two-fold. gamma-Glutamylcysteine synthetase activity (units/g lens) is quite similar in the first three species, whereas the enzyme activity is more than a magnitude less in young adult human lenses, and becomes much less with increasing age and in a high proportion of life-support system organ donors. The enzyme activity was undetectable in a few of the latter lenses. Loss of activity was not due to increased susceptibility to heat denaturation. The low levels of the enzyme, and total loss in some situations, suggest that gamma-glutamylcysteine synthetase may be an Achilles' Heel of human lens metabolism.
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PMID:Activity of glutathione synthesis enzymes in human lens related to age. 613 16

Six factors were analyzed which may be involved in the decline of glutathione synthesis in the aging lens and cataract, with special emphasis placed upon the human lens. The factors included: 1) lability of gamma-glutamylcysteine synthetase, 2) paucity of gamma-glutamylcysteine synthetase in primate lenses as compared to other mammalian lenses, 3) enzyme activity reduction with age in the human lens, 4) rate control by reactant scarcity, especially of cysteine and magnesium ion, 5) rate control by inhibition using 5'-AMP, 5'-ADP and glutathione, and 6) possible dissociation of the multi-enzyme complex. It was concluded that decline of the glutathione synthetic capacity in vivo would be most likely caused by reduction of gamma-glutamylcysteine synthetase activity rather than of glutathione synthetase activity.
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PMID:Lenticular glutathione synthesis: rate-limiting factors in its regulation and decline. 614 Jan 27

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


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