GLUTATHIONE REDUCTASE OF ANIMAL TISSUES

Abstract

It has been known for some time that animal tissues contain systems capable of both the reduction of the oxidized form of glutathione (GSSG) and the oxidation of the reduced form (GSH). Although it is now generally believed that glutathione plays no obligatory rBle in the major electron transport patterns of animal tissues, it appears to be involved as an important substance in the regulation of the activity of enzymes or protein hormones dependent on either -SH or -S-Sgroups for activity (1). Since GSH is readily oxidized in vitro by the cytochrome system of some tissues (2, 3), it might be expected that reducing systems also exist physiologically capable of maintaining constant tissue levels of GSH. Hopkins and Elliott demonstrated that, in addition to a heat-stable system capable of reducing GSSG (protein -SH groups), a heat-labile reducing system also existed in animal tissues (4). In 1932 Mann showed that preparations of Harrison’s glucose dehydrogenase of liver were able to cause the reduction of GSSG in the presence of glucose and a crude nucleotide fraction (5). Meldrum and Tarr found that GSSG was enzymatically reduced by the glucose-6-phosphate dehydrogenase (Zwischenferment) of red blood cells or yeast in the presence of substrate and triphosphopyridine nucleotide (TPN) preparations (6). In 1938 Engelhardt and Barkhash reported that anaerobic oxidation of phosphogluconic acid could occur in yeast maceration juice if GSSG was added, with the resultant production of GSH (7). Since this paper was published, very little additional work appears to have been done on the nature of the enzymatic mechanisms involved in the reduction of GSSG by animal tissues. Bukin has reported that reduced diphosphopyridine nucleotide (DPNH2) reacts rapidly and non-enzymatically with GSSG at physiological pH to produce DPN and GSH (8), a reaction which we were unable to observe in the course of this study. In this paper will be described the results of a survey of dehydrogenase systems capable of causing the reduction of GSSG in animal tissue preparations. It has been found that all animal tissues tested contain an enzyme