Metabolism and Functions of Glutathione in Micro-organisms

Penninckx, Michel; Elskens, Marc

doi:10.1016/s0065-2911(08)60031-4

Cited by 169 publications

(131 citation statements)

References 282 publications

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“…Hydrogen peroxide is a ubiquitous molecule that is formed as a product of many oxidase-mediated reactions and of autooxidation of hemoproteins and flavoproteins (38). As well as being both freely diffusible and reactive itself, H 2 O 2 must be removed from cells to avoid formation of the highly reactive hydroxyl radical.…”

Section: Discussionmentioning

confidence: 99%

Differential Protein S-Thiolation of Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Influences Sensitivity to Oxidative Stress

Grant¹,

Quinn

Dawes³

1999

Molecular and Cellular Biology

145

126

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The irreversible oxidation of cysteine residues can be prevented by protein S-thiolation, in which protein -SH groups form mixed disulfides with low-molecular-weight thiols such as glutathione. We report here the identification of glyceraldehyde-3-phosphate dehydrogenase as the major target of protein S-thiolation following treatment with hydrogen peroxide in the yeast Saccharomyces cerevisiae. Our studies reveal that this process is tightly regulated, since, surprisingly, despite a high degree of sequence homology (98% similarity and 96% identity), the Tdh3 but not the Tdh2 isoenzyme was S-thiolated. The glyceraldehyde-3-phosphate dehydrogenase enzyme activity of both the Tdh2 and Tdh3 isoenzymes was decreased following exposure to H 2 O 2 , but only Tdh3 activity was restored within a 2-h recovery period. This indicates that the inhibition of the S-thiolated Tdh3 polypeptide was readily reversible. Moreover, mutants lacking TDH3 were sensitive to a challenge with a lethal dose of H 2 O 2 , indicating that the S-thiolated Tdh3 polypeptide is required for survival during conditions of oxidative stress. In contrast, a requirement for the nonthiolated Tdh2 polypeptide was found during exposure to continuous low levels of oxidants, conditions where the Tdh3 polypeptide would be S-thiolated and hence inactivated. We propose a model in which both enzymes are required during conditions of oxidative stress but play complementary roles depending on their ability to undergo S-thiolation.Sulfhydryl groups (-SH) play a remarkably broad range of roles in the cell, since the redox status of cysteine residues is involved in both the structure and function of numerous enzymes, receptors, and transcription factors. However, cysteine residues are among the most easily oxidized residues in proteins, and the oxidation of -SH groups is one of the earliest observable events during reactive oxygen species (ROS)-mediated damage (6, 12). The oxidation of -SH groups can result in the formation of protein disulfides (S-S) through two protein cysteines or mixed disulfides between protein-SH groups and a number of low-molecular-weight thiols (protein S-thiolation). While the role of disulfide bond formation in protein folding has been well characterized (see, for example, reference 23), its role during conditions of oxidative stress is unclear. In contrast, protein S-thiolation has been proposed to serve an antioxidant function by preventing the irreversible oxidation of cysteine residues to higher oxidation states (e.g., sulfenic acid) following exposure to ROS (10, 47).Modification of proteins by S-thiolation does not require an enzymatic activity and has been proposed to occur either by the reaction of partially oxidized protein sulfhydryls (thiyl radical or sulfenic acid intermediates) with thiols such as cysteine or glutathione (GSH) or by thiol-disulfide exchange reactions with the oxidized disulfide form of GSH (GSSG) (47). To provide a defense against conditions of oxidative stress, this modification must be reversible. Dethiolatio...

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Section: Discussionmentioning

confidence: 99%

Differential Protein S-Thiolation of Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Influences Sensitivity to Oxidative Stress

Grant¹,

Quinn

Dawes³

1999

Molecular and Cellular Biology

145

126

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“…GSH is synthesized from glutamate, cysteine and glycine. In yeast, the regulation of cytosolic and intramitochondrial redox balances are achieved by alteration of the ratios of GSH to its oxidized dimer GSSG (Gilbert, 1995 ;Penninckx & Elskens, 1993). This redox balance is vital for correct protein folding (Raina & Missiakas, 1997), transcriptional regulation (Demple, 1998) and protection against reactive oxygen species (Meister, 1995a).…”

Section: Introductionmentioning

confidence: 99%

Involvement of glutathione in the regulation of respiratory oscillation during a continuous culture of Saccharomyces cerevisiae

Murray

Engelen

Lloyd³

et al. 1999

Microbiology

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Respiratory oscillation occurred during aerobic continuous culture of Saccharomyces cerevisiae. During oscillation, phase-related changes in NAD(P)H and GSH levels occur. Perturbation of oscillation and inhibition of respiration occurred when GSH or GSSG was injected ; however, there was a phase delay in perturbation in the case of an injection during high respiration. The perturbation phase delay was not apparent when a combination of DL-buthionine-(S,R)-sulphoximine, GSH and 5-nitro-2-furaldehyde was injected. Perturbation by GSH injection caused the intracellular GSH concentration to increase, the GSSG concentration to decrease and the cessation of ethanol uptake. NAD(P)H during perturbation was inversely related to dissolved oxygen. Perturbation by calcium pantothenate and pyridoxal-HCl caused a period of enhanced respiration before oscillation returned. These results suggest that the NAD M /NADH redox is not directly involved in oscillation control and regulation involves glutathione metabolism. Possible regulation points include alcohol dehydrogenase inhibition and/or respiratory-chain inhibition.

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“…Cysteine residues are required for essential and ubiquitous proteins with iron-sulfur (Fe-S) clusters, including cytochromes and aconitase (4,21). In many organisms, the cysteine-containing molecules glutathione and thioredoxin play a major role in maintaining an intracellular reducing environment and protection against oxidative stress (6,14,23,51). The formation of disulfide bonds between cysteine residues is the critical step in the activation of bacterial transcriptional regulators such as OxyR (8,71) and the molecular chaperone Hsp33 (2,34).…”

mentioning

confidence: 99%

Role of a Cysteine Synthase in Staphylococcus aureus

et al. 2004

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The gram-positive human pathogen Staphylococcus aureus is often isolated with media containing potassium tellurite, to which it has a higher level of resistance than Escherichia coli. The S. aureus cysM gene was isolated in a screen for genes that would increase the level of tellurite resistance of E. coli DH5␣. The protein encoded by S. aureus cysM is sequentially and functionally homologous to the O-acetylserine (thiol)-lyase B family of cysteine synthase proteins. An S. aureus cysM knockout mutant grows poorly in cysteine-limiting conditions, and analysis of the thiol content in cell extracts showed that the cysM mutant produced significantly less cysteine than wild-type S. aureus SH1000. S. aureus SH1000 cannot use sulfate, sulfite, or sulfonates as the source of sulfur in cysteine biosynthesis, which is explained by the absence of genes required for the uptake and reduction of these compounds in the S. aureus genome. S. aureus SH1000, however, can utilize thiosulfate, sulfide, or glutathione as the sole source of sulfur. Mutation of cysM caused increased sensitivity of S. aureus to tellurite, hydrogen peroxide, acid, and diamide and also significantly reduced the ability of S. aureus to recover from starvation in amino acid-or phosphate-limiting conditions, indicating a role for cysteine in the S. aureus stress response and survival mechanisms.

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Metabolism and Functions of Glutathione in Micro-organisms

Cited by 169 publications

References 282 publications

Differential Protein S-Thiolation of Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Influences Sensitivity to Oxidative Stress

Differential Protein S-Thiolation of Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Influences Sensitivity to Oxidative Stress

Involvement of glutathione in the regulation of respiratory oscillation during a continuous culture of Saccharomyces cerevisiae

Role of a Cysteine Synthase in Staphylococcus aureus

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