Glutathione-Related Enzymes and Proteins: A Review

Abstract

The tripeptide glutathione is found in all eukaryotic cells, and due to the compartmentalization of biochemical processes, its synthesis takes place exclusively in the cytosol. At the same time, its functions depend on its transport to/from organelles and interorgan transport, in which the liver plays a central role. Glutathione is determined as a marker of the redox state in many diseases, aging processes, and cell death resulting from its properties and reactivity. It also uses other enzymes and proteins, which enables it to engage and regulate various cell functions. This paper approximates the role of these systems in redox and detoxification reactions such as conjugation reactions of glutathione-S-transferases, glyoxylases, reduction of peroxides through thiol peroxidases (glutathione peroxidases, peroxiredoxins) and thiol-disulfide exchange reactions catalyzed by glutaredoxins.

Keywords: cell; glutathione; glutathione enzyme; glutathione system; glutathionylation; redox homeostasis.

Figure 1

Structure of reduced (GSH) and oxidized (GSSG) forms of glutathione.

Figure 2

Involvement of γ-glutamyl transpeptidase (GGT), glutathione-S-transferases (GST), their subfamily of Membrane Associated Proteins in Eicosanoid and Glutathione metabolism (MAPEG), and glyoxylases (Glo) in the intracellular metabolism of GSH. MRP1 (multidrug resistance-associated protein 1) transporter facilitates the unidirectional transport of conjugates.

Figure 3

Basic reaction mechanisms of glutathione peroxidase (GPx), and glutaredoxin in (de)glutathionylation using (GSH)GSSG, respectively, and reduction of GSSG by the activity of glutathione reductase (GR) with reducing the power of NADPH + H⁺. Reduction of peroxiredoxin (Prdx) after disposal of peroxides is ensured by thioredoxin (Trx), which is reduced by consumption of NADPH + H⁺ in catalytic efficiency of thioredoxin reductase (TrxR).