scholarly journals Glutathione replenishment capacity is lower in isolated perivenous than in periportal hepatocytes

1988 ◽  
Vol 254 (2) ◽  
pp. 411-417 ◽  
Author(s):  
Y Kera ◽  
K E Penttilä ◽  
K O Lindros
Keyword(s):  
Glutathione Synthetase ◽  
Synthetase Activity ◽  
Gamma Glutamyl Transpeptidase ◽  
Zonal Distribution ◽  
Significant Difference ◽  
Glutamylcysteine Synthetase ◽  
Gsh Metabolism ◽  
Collagenase Perfusion ◽  
Sulphur Amino Acids ◽  
Glutamyl Transpeptidase

The zonal distribution of GSH metabolism was investigated by comparing hepatocytes obtained from the periportal (zone 1) or perivenous (zone 3) region by digitonin/collagenase perfusion. Freshly isolated periportal and perivenous cells had similar viability (dye exclusion, lactate dehydrogenase leakage and ATP content) and GSH content (2.4 and 2.7 mumol/g respectively). During incubation, periportal cells slowly accumulated GSH (0.35 mumol/h per g), whereas in perivenous cells a decrease occurred (-0.14 mumol/h per g). Also, in the presence of either L-methionine or L-cysteine (0.5 mM) periportal hepatocytes accumulated GSH much faster (3.5 mumol/h per g) than did perivenous cells (1.9 mumol/h per g). These periportal-perivenous differences were also found in cells from fasted rats. Efflux of GSH was faster from perivenous cells than from periportal cells, but this difference only explained 10-20% of the periportal-perivenous difference in accumulation. Furthermore, periportal cells accumulated GSH to a plateau 26-40% higher than in perivenous cells. There was no significant difference in gamma-glutamylcysteine synthetase or glutathione synthetase activity between the periportal and perivenous cell preparations. The periportal-perivenous difference in GSH accumulation was unaffected by inhibition of gamma-glutamyl transpeptidase or by 5 mM-glutamate or -glutamine, but was slightly diminished by 2 mM-L-methionine. This suggests differences between periportal and perivenous cells in their metabolism and/or transport of (sulphur) amino acids. Our results suggest that a lower GSH replenishment capacity of the hepatocytes from the perivenous region may contribute to the greater vulnerability of this region to xenobiotic damage.

Induction of intracellular glutathione in alveolar type II pneumocytes following BCNU exposure

1994 ◽  
Vol 266 (2) ◽  
pp. L125-L130 ◽  
Author(s):  
S. G. Jenkinson ◽  
R. A. Lawrence ◽  
C. A. Zamora ◽  
S. M. Deneke
Keyword(s):  
Intracellular Transport ◽  
Oxidant Stress ◽  
Alveolar Type ◽  
Synthetase Activity ◽  
Type Ii ◽  
Gamma Glutamyl Transpeptidase ◽  
Type Ii Pneumocytes ◽  
Oxidant Damage ◽  
Glutamylcysteine Synthetase ◽  
Glutamyl Transpeptidase

N,N'-bis(2-chloroethyl)-N-nitro-sourea (BCNU) is a potent inhibitor of glutathione reductase (GSSG-Red) activity in both tissues and cells. We examined the effects of treating alveolar type II cells with BCNU and found that a marked decrease in cellular GSSG-Red activity occurred in these cells associated with a time-dependent increase in cellular glutathione (GSH) concentrations. The increase in GSH was not found to be related to changes in cellular gamma-glutamyl transpeptidase activity, gamma-glutamylcysteine synthetase activity, nor increased intracellular transport of cystine. When the BCNU-exposed cells were incubated with hydrogen peroxide to produce oxidant stress, the cells exhibited increased susceptibility to oxidant damage when compared with controls, despite the fact that cellular concentrations of GSH were markedly elevated.

scholarly journals Surgical trauma decreases glutathione synthetic capacity in human skeletal muscle tissue

1998 ◽  
Vol 275 (2) ◽  
pp. E359-E365 ◽  
Author(s):  
Jia-Li Luo ◽  
Folke Hammarqvist ◽  
Kerstin Andersson ◽  
Jan Wernerman
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Redox Status ◽  
Skeletal Muscle Tissue ◽  
Surgical Trauma ◽  
Synthetase Activity ◽  
Glutamylcysteine Synthetase ◽  
Gsh Metabolism ◽  
Synthetic Capacity ◽  
Femoris Muscle

To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values ( P < 0.001) and remained low at 72 h ( P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 ± 10.1 preoperatively to 29.4 ± 13.9 at 24 h postoperatively and to 28.3 ± 15.6 μmol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of γ-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 ± 19.1 preoperatively to 41.0 ± 10.5 24 h postoperatively, P < 0.01, and to 46.0 ± 11.7 μU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.

scholarly journals Carbohydrate deficient transferrin in doping and non-doping sportsmen

2012 ◽  
Vol 153 (13) ◽  
pp. 514-517 ◽  
Author(s):  
György Szabó ◽  
Emil Fraenkel ◽  
Gergely Szabó ◽  
Éva Keller ◽  
István Bajnóczky ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Security Studies ◽  
Gamma Glutamyl Transpeptidase ◽  
In Doping ◽  
Significant Difference ◽  
Carbohydrate Deficient Transferrin ◽  
Sport Clubs ◽  
Glutamyl Transpeptidase ◽  
Regular Alcohol Consumption

The determination of carbohydrate deficient transferrin (CDT) concentration is primarily used in social security studies as a proof of regular alcohol consumption exceeding the amount of 60 grams per day. Aims: The present study was performed to investigate into how carbohydrate deficient transferrin CDT values in serum are affected by the so-called food supplements and chemicals included in doping lists. Methods: The investigation was carried out in 15 bodybuilders of two sport clubs and in 10 boxers. All sportsmen were males. In both groups serum carbohydrate deficient transferrin (CDT%), median red blood cell volume and (MCV) gamma-glutamyl-transpeptidase (GGT) values were measured. Results: The authors found a significant difference between the two groups only in carbohydrate deficient transferrin CDT% that was the CDT% value in bodybuilders was twice as high as in boxers. Conclusion: Not all the details of the specificity of carbohydrate deficient transferrin (CDT) concentration are known, however, the remarkably high sensitivity of the method makes it suitable and probably cost-financially effective for serving as a pre-screening tool in doping tests. Orv. Hetil., 2012, 153, 514–517.

scholarly journals Serum Markers as a Predictor of Hepatic Fibrosis Compared to Fibroscan in chronic hepatitis B Infected Egyptian patients: A Cross-sectional Study

2020 ◽  
Vol 10 (1) ◽  
pp. 69-75
Author(s):  
Rehab Badawi ◽  
Hanan Soliman ◽  
Dina Ziada ◽  
Mohammed Elhendawy ◽  
Sherief Abd-Elsalam ◽  
...  
Keyword(s):  
Rank Correlation ◽  
High Sensitivity ◽  
Serum Markers ◽  
Gamma Glutamyl Transpeptidase ◽  
Cross Sectional ◽  
Gamma Glutamyl ◽  
Significant Difference ◽  
Egyptian Patients ◽  
Chronic Hbv ◽  
Glutamyl Transpeptidase

Background & Aims: The gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR), the gamma-glutamyl transpeptidase to albumin (GAR) and S-index are novel biomarkers suggested to assess liver fibrosis. The aim of the work was to assess the correlation between GGT and other related markers as GAR and GPR among other previous documented markers and the degree of fibrosis and steatosis in chronic HBV Egyptian patients as measured by fibroscan. Materials And Methods: After ethical approval of the protocol, a total of 170 chronic HBV patients were recruited from tropical medicine department, Tanta University. They underwent fibroscan examination for fibrosis and steatosis measurement with concomitant testing of liver functions and complete blood picture. Proposed serum markers were calculated. The relation between these ratios with the fibrosis and steatosis measured by fibroscan were tested using Pearson rank correlation. Results: There was a highly significant positive correlation between gamma-glutamyl transpeptidase and platelet ratio (GPR), GAR, GGT, Fib4, APRI and fibrosis (p=<0.001, <0.001,<0.001,<0.001,0.011 and <0.001 respectively), while there was no correlation with the degree of steatosis (p=0.922,0.66,0.936,0.214,0.591 and 0.760 respectively). Also these markers were significantly higher in patients with higher grades of fibrosis (f2-4) (p= 0.007,0.013,<0.001,0.018,0.029,and 0.002 respectively), they also showed high sensitivity and low specificity in detecting higher grades of fibrosis with no statistically significant difference between the AUC of GPR and GAR (p=0.89). Conclusion: Noninvasive serum markers including GGT, GPR, GAR, Fib4, APRI, and S-index are positively correlated to the degree of fibrosis in CHB patients with high sensitivity and low specificity. They were good negative tests for diagnosis of significant fibrosis.

Regulation of cellular glutathione

1989 ◽  
Vol 257 (4) ◽  
pp. L163-L173 ◽  
Author(s):  
S. M. Deneke ◽  
B. L. Fanburg
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cultured Cells ◽  
Feedback Inhibition ◽  
Reductase Activity ◽  
Transport Systems ◽  
Synthetase Activity ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Glutamyl Transpeptidase

In addition to its participation in a variety of other biochemical reactions, glutathione (GSH) is a major antioxidant. It is regularly generated intracellularly from its oxidized form by glutathione reductase activity that is coupled with a series of interrelated reactions. Synthesis of GSH also takes place intracellularly by a two-step reaction, the first of which is catalyzed by rate-limiting gamma-glutamylcysteine synthetase activity. Intracellular substrates for GSH are provided both by direct amino acid transport and by a gamma-glutamyl transpeptidase reaction that salvages circulating GSH by coupling the gamma-glutamyl moiety to a suitable amino acid acceptor for transport into the cell. Although the liver is a net synthesizer of circulating GSH, organs such as the kidney salvage GSH through the gamma-glutamyl transpeptidase reaction. Intracellular GSH may be consumed by GSH transferase reactions that conjugate GSH with certain xenobiotics. Elevation of cellular GSH levels in cultured cells in response to hyperoxia or electrophilic agents such as diethylmaleate is coupled with an increase in activity of the Xc- transport system for the amino acids cystine and glutamate. Strategies may be developed for protection against oxidant injury by enhancement of transport systems for precursor amino acids of GSH or by providing substrate that circumvents feedback inhibition of GSH synthesis.

scholarly journals Differential effect of cis-platinum (cis-diamminedichloroplatinum) on regulation of liver and kidney haem and haemoprotein metabolism. Possible involvement of γ-glutamyl-cycle enzymes

1986 ◽  
Vol 237 (3) ◽  
pp. 713-721 ◽  
Author(s):  
M D Maines
Keyword(s):  
Enzyme Activities ◽  
Time Course ◽  
Parent Compound ◽  
Synthetase Activity ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Differential Effectiveness ◽  
Glutamylcysteine Synthetase ◽  
Ala Synthetase ◽  
Cytochrome P 450

The treatment of rats with cis-platinum (cis-diamminedichloroplatinum) for 1, 3 or 7 days elicited vastly different responses in the liver and the kidney in activities of enzymes of haem-metabolism pathway and gamma-glutamyl-cycle enzymes. The differences resided in the magnitude, direction and the time course of responses. In general, the liver was by far less severely affected, and when a response was elicited, it displayed an earlier onset (1-3 days), with a return to normal at 7 days. In the kidney, however, the effects were notable after 3 days of treatment, and became more pronounced at 7 days. Specifically, the activity of 5-aminolaevulinic acid (ALA) synthetase and contents of cytochrome P-450 and the microsomal haem were decreased in the liver. In contrast, in the kidney, cytochrome P-450 and haem concentrations were significantly increased, with no change in ALA synthetase activity. The increase in the kidney haem content appeared to reflect an increased formation of haem, as suggested by the elevated activity of ferrochelatase and the concomitant decrease in tissue porphyrin levels. In the kidney, a time-dependent and pronounced inhibition of activities of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione production, and gamma-glutamyl transpeptidase, the first enzyme in glutathione breakdown, were observed. The enzyme activities, 7 days after treatment, were only 40 and 60% of the control values respectively. In contrast, these enzyme activities were not affected in the liver. Complexing cis-platinum with cysteine considerably intensified the entire spectrum of effects of cis-platinum in the kidney. Notably, cytochrome P-450 concentration and haem oxygenase activity were increased to about 3.5 and 6 times the control values, respectively. gamma-Glutamylcysteine synthetase activity was decreased to less than 20% of the control. It is suggested that the differential effectiveness of cis-platinum in the liver and the kidney in alternating haem metabolism is related to the vast differences which exist between these organs in the activities of gamma-glutamyl-cycle enzymes. It is further suggested that this may promote the formation in the kidney, but not in the liver, of a cis-platinum-cysteine complex that is more stable, and thus biologically more effective, than the parent compound.

scholarly journals Assay, purification, properties and mechanism of action of γ-glutamylcysteine synthetase from the liver of the rat and Xenopus laevis

1973 ◽  
Vol 133 (4) ◽  
pp. 667-678 ◽  
Author(s):  
J. S. Davis ◽  
J. B. Balinsky ◽  
J. S. Harington ◽  
J. B. Shepherd
Keyword(s):  
Xenopus Laevis ◽  
Rat Liver ◽  
Gel Filtration ◽  
Deae Cellulose ◽  
Glutathione Synthetase ◽  
Synthetase Activity ◽  
Protamine Sulphate ◽  
Ping Pong ◽  
Glutamylcysteine Synthetase ◽  
Sequential Mechanism

1. An improved radioassay for glutathione synthetase and γ-glutamylcysteine synthetase was developed. 2. Xenopus laevis liver γ-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 γ-glutamylcysteine synthetase was purified 11400-fold by a procedure similar to that employed for the Xenopus laevis enzyme. 4. Rat liver γ-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 γ-glutamylcysteine. The results for the rat liver enzyme are consistent with a Tri Tri sequential mechanism.

Subcellular distribution of PRibPP synthetase activity of rat intestinal mucosa

1980 ◽  
Vol 239 (4) ◽  
pp. G266-G271
Author(s):  
L. C. Yip ◽  
A. K. Yeh ◽  
M. E. Balis
Keyword(s):  
Intestinal Mucosa ◽  
Brush Border ◽  
Subcellular Distribution ◽  
Hypoxanthine Phosphoribosyltransferase ◽  
Synthetase Activity ◽  
Coupled Transport ◽  
Gamma Glutamyl Transpeptidase ◽  
Tip Cells ◽  
Glutamyl Transpeptidase ◽  
Crypt Cells

5-Phosphoribosyl 1-pyrophosphate synthetase (PRibPP synthetase EC 2.7.6.1) isolated from rat intestinal mucosa was found to be membrane associated. The subcellular distribution of PRibPP synthetase activity seems to parallel that of gamma-glutamyl transpeptidase, indicating it to be in the brush border. The tip cells of rat intestinal mucosa were richer in PRibPP synthetase than the crypt cells. Chromatography of a Triton-solubilized particulate fraction unmasked a peak of hypoxanthine phosphoribosyltransferase activity that was not detectable before. The activity, too, was concentrated in the brush border. The coexistence of these two activities in the fraction of the bowl involved in absorption has led to the suggestin that the synthetase and phosphoribosyl-transferase are part of a coupled transport system.

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