Kinetic Mechanism and Molecular Properties of Glutathione Reductase
Berivan TANDOĞAN*, N. Nuray ULUSU*^,°
* Hacettepe University, Faculty of Medicine, Department of Biochemistry 06100 Ankara, Turkey

^oCorresponding Author

Summary

Glutathione reductase (GR) is a crucial enzyme (EC 1.6.4.2) that reduces glutathione disulfide (GSSG) to the sulfhydryl form GSH by the NADPH-dependent mechanism, an important cellular antioxidant system. Due to its significance, the enzyme has been purified from a number of animals, plants and microbial sources and studied in an effort to identify and explain its structure, kinetic mechanism and molecular properties since 1935. The kinetic mechanism of GR has been studied by several investigators and several models have been proposed for this enzyme. The kinetic mechanism is known to be a ping-pong/sequential ordered hybrid model. GR is a homodimeric flavoprotein and contains two FAD molecules as a prosthetic group, which is reducible by NADPH. The estimated molecular weight of the dimeric enzyme ranges from 100 to 120 kDa. Stability of GR has been tested in various organisms in a variety of ways and it was found that GR is one of the thermostable enzymes. Bovine liver and kidney cortex GR activity are relatively stable at high temperatures. GR belongs to the defense system protecting the organism against chemical and oxidative stress. Deficiency of the enzyme is characterized by hemolysis due to increased sensitivity of erythrocyte membranes to H₂O₂ and contributes to oxidative stress, which plays a key role in the pathogenesis of many diseases. Many studies have been carried out to explain the interaction of GR with drugs or chemicals and diseases. This review focuses on the molecular properties and kinetic mechanism of GR.

Key Words :
Glutathione reductase, oxidative stress, purification, kinetic mechanism, molecular properties.