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Glutathione and Thiols

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Abstract

Oxidation of the antioxidant glutathione (GSH) to a disulfide (GSSG) has long been an indicator of oxidative stress. GSH is also critical in the detoxification of xenobiotics (drugs, pollutants, carcinogens) through a broad range of reactions with GSH- dependent enzymes containing a redox sensitive cysteine (Cys) residue that undergoes reversible oxidation and reduction at the active site: GSH reductase (GR), glutaredoxin (Grx), and the families of GSH peroxidases (Gpxs) and GSH-S-transferases (GSTs). GSH and GSSG are also involved in many cellular processes termed S-glutathionylation where disulfide bonds are formed with protein Cys residues that subsequently alter enzymatic activity or protein function. The equipoise of GSH/GSSG is pivotal in signal transduction pathways mediated by reaction of reactive oxygen species (ROS) with crucial protein Cys residues. ROS-dependent signaling also involves reduced/oxidized thiol pairs including thioredoxin (Trx-SH/Trx-SS) and Cys with its oxidized form cystine (CySS). Although not in equilibrium, these thiol/disulfide couples are organized into redox circuits with cross-talk. When these redox circuits are disrupted, critical redox active Cys sites become oxidized and protein functions are perturbed. Understanding the roles of redox signaling and redox homeostasis for GSH and other thiol pairs in the responses of the organelle or cell to redox-active chemicals is central to determining the effects of such chemicals on macromolecular structure, regulation, and signaling during the life cycle. Through a better mechanistic understanding, the roles for redox homeostasis of thiol pairs like GSH in the resilience and adaptability to diet and environmental exposures are likely to emerge.

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Abbreviations

Cys:

Cysteine

CySS:

Cystine

GCL:

γ-Glutamylcysteine Ligase

GGT:

γ-Glutamyl transferase

GSH:

Glutathione (reduced)

GSSG:

Glutathione (oxidized)

Gpx:

Glutathione Peroxidase

GR:

Glutathione Reductase

GS:

Glutathione Synthase

Grx:

Glutaredoxin

GST:

Glutathione S-transferase

H2O2 :

Hydrogen Peroxide

Prdx:

Peroxiredoxin

ROS:

Reactive oxygen species

Trx:

Thioredoxin

TrxR:

Thioredoxin Reductase

VOC:

Volatile Organic Compounds

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Authors and Affiliations

  1. Department of Pediatrics, Emory University, Atlanta, GA, USA

    Lou Ann S. Brown

  2. Department of Medicine, Emory University, Atlanta, GA, USA

    Dean P. Jones

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Correspondence to Lou Ann S. Brown .

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  1. Center for Environmental & Human Toxicology, University of Florida, Gainesville, Florida, USA

    Stephen M. Roberts

  2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

    James P. Kehrer

  3. Department of Nutrigenomics, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Thüringen, Germany

    Lars-Oliver Klotz

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Brown, L.A.S., Jones, D.P. (2015). Glutathione and Thiols. In: Roberts, S., Kehrer, J., Klotz, LO. (eds) Studies on Experimental Toxicology and Pharmacology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-19096-9_7

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