Glutathione reductase reaction mechanism

Mechanism of the flavin-dependent glutathione reductase reaction. 

In order to be recycled, GSSG has to be reduced by glutathione reductase. The mechanism of the reaction has been resolved mainly by X-ray diffraction studies [15]. From the juxtaposition of the reactive moiety, it appears that the electrons from dihydroflavin adenine dinucleotide (FADH) will reduce an intramolecular disulfide bond in the enzyme forming 2 SH-groups which in turn will reduce the GSSG disulfide. 

Reaction Mechanism and Kinetic Constants for a Reaction Catalyzed by Glutathione Reductase... 

Glutathione reductase amino acid composition, 102,104,105 cystine residues, 104 kinetic studies, 138-141 mechanism, 94, 97-98,134 metabolic functions, 129-133 reaction catalyzed, 92 reduction of, 112, 113 specificity of, 92-93 coenzymes and, 94 thiol groups, 141-142 two-electron-reduced enzyme, properties, 133-138... 

Figure 15-12 Probable reaction mechanism for lipo-amide dehydrogenase and glutathione reductase. See C63 Pai and Schulz.

The normal catalytic process involves the sequence I- -II->-III->-IV- -I, while the steps IV- V- -VI- -III may also be part of the overall reaction. Thelander (131) has pointed out that the reaction mechanism of thioredoxin reductase differs from those of glutathione reductase and lipoyldehydrogenase because during the anaerobic titration of thioredoxin reductase no flavin semiquinone intermediate could be detected. Although thioredoxin reductase contains two subunits only one octapeptide... 

Schulz, G.E., Pai, E.F. (1983). The catalytic mechanism of glutathione reductase as derived from X-ray diffraction analyses of reaction intermediates, J. Biol. Chem. 258 1752. 

The induction of DNA strand breaks and chromosomal aberrations by cadmium in mammalian cells was suppressed by antioxidants and antioxidant enzymes, indicating the involvement of ROS [34—36], Since the extent of ROS and damage to cellular macromolecules depends on the equilibrium between their generation and detoxification or repair, respectively, the occurrence of oxidative DNA damage is assumed to be due to an inhibition of the antioxidant defense by cadmium, such as the antioxidant enzymes catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase. One other mechanism proposed consists in the displacements of redox active metal ions, e.g., Fe ", for example in metallothionein, giving rise to Fenton reactions [35-37]. 

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