Glutathione reductase (GSR) is an enzyme that helps protect cells against the ravages of oxidative stress. Oxidized products, such as free radicals and peroxides, can damage cellular components, cause mutations, and possibly accelerated aging. They are particularly damaging to the membranes of red blood cells and can cause them to burst open, bringing about hemolytic anemia. Reduced glutathione can reverse this oxidation, but it becomes oxidized in the process. GSR uses other cellular components to bring the glutathione back to its reduced state so it can continue to function as a cellular antioxidant.
GSR enzymes are ubiquitous and present in all mammalian cells. This type of enzyme has a molecule of sulfur at its active site. Reduced glutathione has a hydrogen group bound to this sulfur, and is referred to as GSH. If glutathione becomes oxidized, the sulfur groups each lose an electron and become bound together as GSSG.
For glutathione reductase to reduce the oxidized glutathione to the GSH that the cells need, a compound called NADPH is required. It donates a hydrogen group. This results in two molecules of GSH being generated for each molecule of GSSG.
In most cells, many oxidative and reductive reactions take place in the mitochondria, the cell’s furnace. Red blood cells, however, lack mitochondria. They are thus particularly vulnerable to being oxidized. If the cells lack adequate amounts of glutathione reductase, the membranes can become oxidized and break. This loss of red blood cells can lead to the blood disease known as hemolytic anemia.
There can be several reasons for having inadequate amounts of functioning glutathione reductase. The cells might have enough of the GSR, but they might lack adequate amounts of NADPH. The original source of this cofactor is from the breakdown of glucose in the pentose phosphate pathway. Some people lack an enzyme in this pathway known as glucose-6-phosphate dehydrogenase. This error in metabolism can indirectly lead to an inadequate amount of NADPH, and thus there is not enough active glutathione reductase in the red blood cells.
An inadequate amount of riboflavin can be another reason for lowered amounts of glutathione reductase. This can be caused by inadequate amounts of riboflavin in the diet. Another possibility is that the person may be consuming enough riboflavin, but might have a metabolic problem absorbing vitamins. A few people have a genetic predisposition to make inadequate amounts of glutathione reductase, but this condition is very rare.