The Recycling of Glutathione

Reduced (anti-oxidized) glutathione (GSH) is used by glutathione peroxidase (a selenium-dependent enzyme) to detoxify hydrogen peroxide (H2O2). In this process, the oxidation power of hydrogen peroxide is transferred to oxidized glutathione (GSSG). In other words, H2O2 moves down while GSH moves up. While GSSG still has oxidizing power, it is significantly less than that of H2O2. GSSG is recycled by glutathione reductase using NADPH. In the process, NADPH is converted into NADP+ (the oxidized form of NADPH). The regenerated GSH is then ready to detoxify more hydrogen peroxide.

When the antioxidant defense system is functioning properly, most of it’s components are present in their reduced form H2O2, GSH, and NAHPH). If there is a malfunction, then the oxidized components H2O2, GSSG and/or NADP) tend to accumulate — with adverse effects. The entire process is driven by energy production at the cellular level, which involves proper thyroid hormone levels, healthy mitochondrial function, and an active pentose-phosphate metabolic pathway. The pentose-phosphate pathway is especially important for providing NADPH for red blood cells and hepatocytes (liver cells). In some populations, one of the key enzymes in the pentosephosphate pathway (glucose-6-phosphate dehydrogenase, or G6PD) is frequently deficient due to mutations. Over 300 human variants of G6PD have been identified! With diminished G6PD activity, the supply of NADPH is impaired, GSSG levels tend to accumulate, and control of hydrogen peroxide (and superoxide) is impaired. This results in formation of methemoglobin (an oxidized and inactive form of hemoglobin), and if severe enough, hemolytic anemia (wholesale destruction of red blood cells). ——SWF