Glutathione Reductase: Regulation and Role in Oxidative Stress

INTRODUCTION Since its presence was reported in a variety of animal tissues over 100 years ago (de Rey-Pailhade 1888), glutathione (or analogs such as homoglutathione; Zopes et al. 1993) has been shown to be very widespread; it is present in plants, animals, fungi, and a large number of prokaryotic species (Mannervik et al. 1989). In all organisms where it is present, glutathione (γ-L-glutamyl-L-cysteinylglycine; Fig. 1) is the major free thiol-containing compound, reaching millimolar concentrations (Dolphin et al. 1989). In addition, wherever glutathione is found, so too is the enzyme glutathione reductase (GR; E.C.1.6.4.2) which reduces the oxidized form of glutathione, glutathione disulfide (GSSG), to reduced glutathione (GSH; Fig. 1). In organisms where glutathione is not present, some other free thiol or H 2 S is found in place of GSH, along with an enzyme that reduces the oxidized form of that compound; e.g., trypanosomes do not contain glutathione, but instead contain trypanothione and the corresponding enzyme trypanothione reductase (Perham et al. 1991). Functions of Glutathione We do not provide in this chapter a detailed description of the biochemical, chemical, and physiological properties of glutathione. The subject is covered in great detail by Dolphin et al. (1989), albeit with a bias toward a mammalian and medical perspective. For a consideration of the functions of glutathione from a plant perspective, the reader is referred to Alscher (1989). However, a brief description of the roles of glutathione is required. Reduced glutathione is a one-electron donor, and its functions can be divided into two broad categories...