scholarly journals Effect of oxidized glutathione on the inhibition of glucose-6-phosphate dehydrogenase by NADPH

1986 ◽  
Vol 234 (3) ◽  
pp. 741-741 ◽  
Author(s):  
Barry Halliwell
Keyword(s):  
Oxidized Glutathione ◽  
Glucose 6 Phosphate Dehydrogenase

scholarly journals Pathways for the reduction of oxidized glutathione in the Plasmodium falciparum-infected erythrocyte: can parasite enzymes replace host red cell glucose-6-phosphate dehydrogenase?

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 827-830 ◽  
Author(s):  
EF Jr Roth ◽  
S Schulman ◽  
J Vanderberg ◽  
J Olson
Keyword(s):  
Plasmodium Falciparum ◽  
Oxidant Stress ◽  
Reduction Rate ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Red Cells ◽  
Host Cells ◽  
Functional Assay ◽  
Red Cell ◽  
Oxidized Glutathione ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Plasmodium falciparum-infected human red cells possess at least two pathways for the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH): (1) the glucose-6-phosphate dehydrogenase (G6PD) pathway and (2) the glutamate dehydrogenase (GD) pathway using glutamate as a substrate. Uninfected erythrocytes lack the GD pathway. The NADPH generated can be used to reduce oxidized glutathione (GSSG), which accumulates in the presence of an oxidative stress. In red cell G6PD deficiency, this pathway is reduced or absent, and the host cells as well as the parasites within them are vulnerable to oxidant stress. In view of the presence of the GD pathway in parasitized red cells and the recent description of a parasite-derived G6PD enzyme, we have asked whether the pathways for the reduction of GSSG provided by the parasite can substitute for the host G6PD in red cells deficient in G6PD activity. We have devised a functional assay in which the reduction rate of GSSG is monitored in the presence of buffered infected or control red cell lysates and substrates. Infected G6PD-deficient erythrocytes were obtained from in vitro cultures after a single prior growth cycle of the parasites in G6PD deficient cells to eliminate contaminating normal red cells. The results show that only parasitized red cells can reduce GSSG via the GD pathway. In parasitized G6PD Mediterranean red cells (completely G6PD-deficient), there is a detectable GSSG reduction via the G6PD pathway, not found in uninfected lysates from the same individual. In G6PD A- (African type, featuring partial deficiency), a small increment in the G6PD-dependent reduction of GSSG can also be detected. However, when compared to G6PD normal red cells, the activities from the parasite-derived pathways are small and could not be considered substitutes for normal host enzyme activity. It is concluded that while the plasmodium provides additional pathways for the generation of NADPH that may serve its own metabolic needs, the host red cells and hence the parasite itself remain vulnerable to oxidant stress.

Glutathione metabolism in heart and liver of the aging rat

1994 ◽  
Vol 72 (1-2) ◽  
pp. 58-61 ◽  
Author(s):  
M. Stio ◽  
T. Iantomasi ◽  
F. Favilli ◽  
P. Marraccini ◽  
B. Lunghi ◽  
...  
Keyword(s):  
Rat Heart ◽  
Reduced Glutathione ◽  
Age Groups ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Glutathione S Transferase ◽  
Age Related ◽  
Glutamylcysteine Synthetase ◽  
Old Rats ◽  
Glucose 6 Phosphate Dehydrogenase

A comprehensive study on glutathione metabolism in rat heart and liver as a function of age was performed. In the heart, reduced glutathione, total glutathione, and the glutathione redox index showed a decrease during aging, while oxidized glutathione levels increased in 5-month-old rats with respect to the young animals and remained quite constant in 14- and 27-month-old rats. In the liver, the highest levels of reduced glutathione were found in the 2-month-old rats, while oxidized glutathione reached a peak at 5 months. Glutathione-associated enzymes showed age-related changes. Glutathione peroxidase, unaffected by aging in the heart, decreased in the liver of the 27-month-old rats. In the heart and the liver, the highest values of glutathione S-transferase were found at 5 months and 27 months, respectively. Glucose-6-phosphate dehydrogenase followed a similar trend in both heart and liver. Glutathione reductase also showed the same behaviour in heart and in liver, increasing in old rats with respect to the other age groups. A decrease in γ-glutamylcysteine synthetase was found in the heart and liver of 27-month-old rats in comparison with the 2-month-old ones. In conclusion, a decreased antioxidant capability has been demonstrated in both heart and liver of old rats.Key words: glutathione metabolism, age, rat heart, rat liver.

scholarly journals A critical appraisal of the effect of oxidized glutathione on hepatic glucose 6-phosphate dehydrogenase activity

1983 ◽  
Vol 214 (3) ◽  
pp. 959-965 ◽  
Author(s):  
H R Levy ◽  
M Christoff
Keyword(s):  
Glutathione Reductase ◽  
Dehydrogenase Activity ◽  
Rat Liver ◽  
Critical Appraisal ◽  
Oxidized Glutathione ◽  
Assay Procedure ◽  
Low Concentrations ◽  
Hepatic Glucose ◽  
Spurious Effect ◽  
Glucose 6 Phosphate Dehydrogenase

Experiments were undertaken to elucidate the mechanism of the reversal of NADPH inhibition of rat liver glucose 6-phosphate dehydrogenase by oxidized gluthathione alone and in combination with a putative cofactor described by Eggleston & Krebs [(1974) Biochem. J. 138, 425-435]. Evidence is presented that this reversal is largely an artifact, caused by the incorrect application of a control assay procedure and a spurious effect of Zn2+ (added in order to inhibit glutathione reductase) in crude enzyme solutions. When the proper assay procedure is used and glutathione reductase is inhibited with low concentrations of Hg2+, glutathione addition has no effect on NADPH inhibition of glucose 6-phosphate dehydrogenase. No evidence was found for the existence of a cofactor that mediates an effect of glutathione on glucose 6-phosphate dehydrogenase.

scholarly journals Regulation of the oxidative phase of the pentose phosphate cycle in mussels

1978 ◽  
Vol 170 (3) ◽  
pp. 577-585 ◽  
Author(s):  
S Rodriguez-Segade ◽  
M Freire ◽  
A Carrion
Keyword(s):  
Inorganic Ions ◽  
Pentose Phosphate ◽  
Oxidized Glutathione ◽  
Phosphogluconate Dehydrogenase ◽  
Pentose Phosphate Cycle ◽  
Intracellular Concentrations ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Substrate Concentrations

1. The mechanisms that control the oxidative phase of the pentose phosphate cycle in mussel hepatopancreas were investigated. 2. The effects of GSSG (oxidized glutathione) on the inhibition of glucose 6-phosphate dehydrogenase by NADPH [Eggleston & Krebs (1974) Biochem. J. 138, 425-435] extend to 6-phosphogluconate dehydrogenase. 3. The effect of GSSG on both enzymes increases as the [NADP+1]/[NADPH] ratio decreases; greater percentage deinhibition always was obtained for 6-phosphogluconate dehydrogenase. 4. Increasing concentration of GSSG increased the percentage deinhibition. This effect is more pronounced with 6-phosphogluconate dehydrogenase. 5. We confirmed the apparent imbalance between the activities of the two enzymes [sapag-Hagar, Lagunas & Sols (1973) Biochem. Biophys. Res. Commun, 50, 179-185] in the presence of 10mM-Mg2+. 6. The imbalance practically disappears when the substrate concentrations are less than saturating and Mg2+ approaches physiological concentrations. 7. The addition of GSSG at physiological concentrations allows the activities of both enzymes to be measured at high [NADPH]/[NADP+] ratios ratios and the co-operative action of GSSG and Mg2+ on the imbalance between the two enzymes to be verifed. 8. The control of the activity of the two enzymes of the pentose cycle could be carried out by deinhibition of the two dehydrogenases and by the intracellular concentrations of substrates and inorganic ions.

scholarly journals The transport of oxidized glutathione from the erythrocytes of various species in the prescence of chromate

1969 ◽  
Vol 114 (4) ◽  
pp. 833-837 ◽  
Author(s):  
Satish K. Srivastava ◽  
Ernest Beutler
Keyword(s):  
Hydrogen Peroxide ◽  
Glutathione Reductase ◽  
Pyruvate Kinase ◽  
Transport Rate ◽  
Oxidized Glutathione ◽  
Phosphogluconate Dehydrogenase ◽  
Presence And Absence ◽  
Glucose 6 Phosphate Dehydrogenase

1. Erythrocytes from normal and glucose 6-phosphate dehydrogenase-deficient humans were subjected to hydrogen peroxide diffusion to oxidize the GSH. Studies were carried out in the presence and absence of chromate to inhibit glutathione reductase and with or without the addition of glucose. 2. The GSH content of erythrocytes from other species was oxidized by subjecting them to hydrogen peroxide diffusion in the presence of chromate and glucose. 3. Chromate (1·3mm) inhibited glutathione reductase by about 80%, whereas glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, hexokinase, phosphofructokinase and pyruvate kinase were not inhibited. 4. The GSSG formed was transported from the erythrocytes to the medium. 5. The transport rate of GSSG from glucose 6-phosphate dehydrogenase-deficient erythrocytes subjected to hydrogen peroxide diffusion in the presence of chromate was comparable with that from normal and glucose 6-phosphate dehydrogenase-deficient erythrocytes. 6. The rate of transport of GSSG from erythrocytes of various species studied could be ranked: pigeon>rabbit>rat>donkey>man>dog>horse>sheep>chicken>fish.

Changes in glutathione status and 3,5,3'-triiodothyronine action in livers of rats given cysteine-deficient diets

1989 ◽  
Vol 61 (2) ◽  
pp. 301-307 ◽  
Author(s):  
H. Garcin ◽  
C. Suberville ◽  
P. Higueret ◽  
D. Higueret
Keyword(s):  
Malate Dehydrogenase ◽  
Nuclear Protein ◽  
Protein Complexes ◽  
Reduced Glutathione ◽  
Scatchard Analysis ◽  
Oxidized Glutathione ◽  
Deficient Diet ◽  
Young Rats ◽  
Glutathione Status ◽  
Glucose 6 Phosphate Dehydrogenase

1. For a period of 32 d young rats were given a diet containing (g/kg) 220 casein, 120 casein +1.93 L-cysteine (Cys), or 120 casein.2. The formation of 3,5,3'-triiodothyronine (T3)-nuclear protein complexes was reduced in rats fed on the Cys-deficient diet.3. Scatchard analysis showed that decreased formation of T3 -nuclear protein complexes was due to a decreased affinity of T3 receptors; this decrease was induced, at least in part, by a reduced glutathione content.4. In rats fed on the Cys-deficient diet there was an expected decrease in growth but an unexpected increase in the activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) (EC 1.1.1.40). It is suggested that this increase is related to an increased oxidized glutathione: reduced glutathione ratio.

scholarly journals Investigation of the Defect in a Variant of Hereditary Methemoglobinemia

Blood ◽  
1962 ◽  
Vol 19 (1) ◽  
pp. 60-74 ◽  
Author(s):  
PHILIP L. TOWNES ◽  
MARTIN MORRISON
Keyword(s):  
Lactic Acid ◽  
Glutathione Reductase ◽  
Dehydrogenase Activity ◽  
Reduced Glutathione ◽  
Coupled System ◽  
Oxidized Glutathione ◽  
Total Glutathione ◽  
Primary Defect ◽  
New Variant ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract 1. Further evidence has been presented to confirm the fact that the methemoglobin found in a new variant of hereditary methemoglobinemia was normal methemoglobin. 2. The reduced glutathione content of the red cells of this variant was less than 50 per cent of normal. 3. The total glutathione and oxidized glutathione were proportionally deficient. 4. The low glutathione content did not result from abnormal degradation nor lack of adequate reducing mechanisms. The primary defect was considered to be one of inadequate glutathione synthesis. 5. Various enzymes were assayed, including the following: glucose 6-phosphate dehydrogenase, lactic acid dehydrogenase, triosephosphate dehydrogenase, glutathione reductase, glucose 6-phosphate dehydrogenase-glutathione reductase (coupled system) and catalase. 6. This variant of methemoglobinemia was considered to result from inadequate synthesis of glutathione. The deficiency of this essential co-factor apparently results in an impairment of triosephosphate dehydrogenase activity and consequently insufficient reduction of DPN, an essential component of the DPNH-dependent methemoglobin reductase.

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