A glutathione reductase

A12. Asnis, R. E., A glutathione reductase from Escherichia coli. J. Biol. Chem. 213, 77-85 (1955). 

Halliwell, B., and C. H. Foyer Properties and physiological function of a glutathione reductase purified from spinach leaves by affinity chromatography. Planta 139, 9 (1978). 

FIGURE 6.34 Sheet structures formed from andparallel arrangements of /3-strands, (a) Streptomyces suh i x Xu inhibitor, (b) glutathione reductase domain 3, and (c) the second domain of glyceraldehyde-3-phosphate dehydrogenase represent minimal andparallel /S-sheet domain structures. In each of these cases, an andparallel /S-sheet is largely exposed to solvent on one face and covered by helices and random coils on the other face. (Jane Richardson)... 

The FAD-dependent enzyme glutathione reductase plays a role in the antioxidant system. Glutathione reductase restores reduced glutathione (GSH), the most important antioxidant in erythrocytes, from oxidized glutathione (GSSG) [1, 2]. 

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (R-,free radical PUFA-00-, peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase Aj PUFA-OH, hydroxy polyunsaturated fatty acid TocOH, vitamin E (a-tocopherol) TocO, free radical of a-tocopherol Se, selenium GSH, reduced glutathione GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase PUFA-H, polyunsaturated fatty acid.)...

Although riboflavin is fundamentally involved in metabolism, and deficiencies are found in most countries, it is not fatal as there is very efficient conservation of tissue riboflavin. Riboflavin deficiency is characterized by cheilosis, lingual desquamation and a seborrheic dermatitis. Riboflavin nutritional status is assessed by measurement of the activation of erythrocyte glutathione reductase by FAD added in vitro. 

Glutathione reductase (GR) catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH) using NADPH provided from the hexose monophosphate pathway. GR, a ubiquitous flavoenzyme, maintains a high value of two for the GSH/GSSG ratio in the red blood cells. l,3-Bis(2-chloroethyl)-nitrosourea (BCNU) selectively inhibits cellular GR. GR is composed of two identical subunits, each of molecular mass 50 kDa (S8). The three-dimensional structure and mechanism of catalysis have been established for human GR (K17). 

The glutathione redox system is an essential player in controlling the redox state within the cell, the glutathione/glutathione reductase pathway attempts to keep a stable cellular redox balance... 

Since glutathione reductase is a cornerstone of the malaria parasite antioxidant defence and repair mechanism, it is a potential target for antimalarial and cytostatic agents. 

The importance of having adequate supplies of NADPH for the regeneration of these various enzymes cannot be over emphasized. In normal situations this cofactor can be adequately provided by the reductive pentose phosphate pathway. Monitoring the activity of the pentose phosphate pathway has been proposed as a unique way to study the metabolic response to oxidative stress, since the glutathione peroxidase activity is coupled via glutathione reductase to the enzyme glucose-6-phosphate dehydrogenase (Ben Yoseph et ah, 1994). 

III. Glutathione reductase (EC 1.6.4.2) It is a flavoprotein that catalyzes the NADPH-dependent reduction of oxidized glutathione (GSSG) to glutathione (GSH). This enzyme is essential for the GSH redox cycle which maintains adequate levels of reduced cellular GSH. A high GSH/GSSG ratio is essential for protection against oxidative stress. 

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