Medicinal Mushroom Ingredients

Glutothione Reductase and Glutathione Peroxidase

“These are enzymes that have antioxidant effects in biological and biochemical systems. The antioxidant defense system protects the cell against oxidative damage of free radicals or other reactive molecules.”Jan 31, 2020  This is in turn helps to prevent lipid peroxidation and maintain intracellular homeostasis as well as redox balance

First line defense antioxidants

These are a collection of antioxidants that act to suppress or prevent the formation of free radicals or reactive species in cells. They are very fast in neutralizing any molecule with the potential of developing into a free radical or any free radical with the ability to induce the production of other radicals. Three key enzymes: superoxide dismutase, catalaseand glutathione peroxidase are top on the list. These enzymes respectively dismutate superoxide radical, breakdown hydrogen peroxides and hydroperoxides to harmless molecules (H₂O₂/alcohol and O₂). The class also includes metal ion binding proteins like transferrin and caeruloplasmin which chelate or sequester iron and copper respectively, consequently preventing them from free radical formation.

2.2. Second line defense antioxidants

This group of antioxidants is often referred to as scavenging antioxidants. They scavenge active radicals to inhibit chain initiation and break chain propagation reactions. They neutralize or scavenge free radicals by donating electron to them, and in the process become free radicals themselves but of lesser damaging effects. These ‘new radicals’ are easily neutralized and made completely harmless by other antioxidants in this group. Most antioxidants including ascorbic acid, uric acid, glutathione, which are hydrophilic and alpha tocopherol (vitamin E) and ubiquinol which are lipophilic belong to this category.

2.3. Third line defense antioxidants

This category of antioxidants only comes into play after free radical damage has occurred. They are de novo enzymes which repair the damage caused by free radicals to biomolecules and reconstitute the damaged cell membrane. They are a group of enzymes for repair of damaged DNA, protein and lipids. They also do a sort of ‘clean up duty’, they recognize, breakdown and remove oxidized or damaged proteins, DNA and lipids, to prevent their accumulation which can be toxic to body tissues. Common examples include The DNA repair enzyme systems (polymerases, glycosylases and nucleases), proteolytic enzymes (proteinases, proteases and peptidases) which are located both in cytosol and mitochondria of mammalian cells.

2.4. Fourth line defense antioxidants

The action of these ‘antioxidants’ basically involves an adaptation mechanism in which they utilize the signals required for free radicals production and reaction to prevent the formation or reaction of such free radicals. The signal generated from the free radical formed induces the formation and transport of an appropriate antioxidant to the right site.⁸

Superoxide dismutase, catalase and glutathione peroxidase are antioxidant enzymes which do not only play fundamental but indispensable role in the antioxidant protective capacity of biological systems against free radical attack. The superoxide radical (^∗O₂) or singlet oxygen radical (¹O₂⁻) generated in tissues through metabolism or reactions in cells is catalytically converted to hydrogen peroxide (H₂O₂) and molecular oxygen (O₂) by superoxide dismutase (SOD). H₂O₂ when accumulated is toxic to body tissues or cells. Also, in the presence of Fe²⁺ it is converted to deleterious hydroxyl radical (^∗OH) through Fentonreaction. In order to prevent this phenomenon, catalase (another antioxidant enzyme) which is abundant in the peroxisomes breaks down H₂O₂ into water and molecular oxygen, consequently curtailing free radical-induced damage (Fig. 3). However, catalase is absent in the mitochondria, hence the reduction of H₂O₂ to water and lipid peroxides to their corresponding alcohols is carried out by Glutathione Peroxidase (GPx). This collective protective effort is termed first line antioxidant defense, and the antioxidants involved are referred to as first line defense antioxidants. The role and effectiveness of the first line defense antioxidants which basically include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) is therefore important and indispensable in the entire defense strategy of antioxidants, especially in reference to super oxide anion radical (^∗O₂) which is perpetually generated in normal body metabolism through several processes.

Glutathione peroxidases (GPx, EC 1.11.1.9)

Glutathione Peroxidase (GPx) is an important intracellular enzyme that breakdown hydrogen peroxides (H₂O₂) to water; and lipid peroxides to their corresponding alcohols mainly in the mitochondria and sometimes in the cytosol.³⁹ Most times, its activity depends on a micronutrient cofactor known as selenium. For this reason, GP_X is often referred to as a selenocysteine peroxidase. The enzyme plays a more crucial role of inhibiting lipid peroxidation process, and therefore protects cells from oxidative stress.²⁵

According to Morón and Cortázar, there are at least eight GPx enzymes in human, GPx1–GPx8. The GPx 1–8 genes are mapped to chromosomes 3, 14, 5, 19, 6, 6, 1 and 5 respectively.⁴⁴ Among the glutathioneperoxidases, GPx1 is the most abundant selenoperoxidase and is present virtually in all cells.⁴⁵GPx2 is found much more in the gastrointestinal tract primarily in the intestine.46, 47 The kidney relative to other tissues is the primary location for GPx3, though; the enzyme is also present in extracellular fluids as a glycoprotein.⁴⁸ Most forms of GPx are tetrameric in structure but GPx4 which is often regarded as phospholipid hydroperoxide is a monomer and differ in substrate specificity. This is because Gpx4 is the only GPx enzyme that breaks down phospholipid hydroperoxides. The enzyme also has a mitochondrial isoform that mediates the apoptotic response to oxidative stress⁴⁹ and has a peroxidase independent structural role in sperm maturation.45, 50 GPx5 from both humans and rodents and Rodent GPx6 differ from other glutathione peroxidases in that their activities are independent of Selenium.⁵¹ This invariably implies that these forms of GPx may not be able to effectively scavenge H₂O₂, a feature which is characteristic of the selenium-dependent glutathione peroxidases.⁵²

The clinical importance of GPx has been underlined by a number of studies. Chabory et al. postulated that individuals with lower GPx activity are predisposed to impaired antioxidant protection, which leads to oxidative damage to membrane fatty acid s and functional proteins (Fig. 5), and by inference, neurotoxic damage.⁵³ Forgione and colleagues had previously hypothesized that GP_X1 deficiency directly induces an increase in vascular oxidative stress, with attendant endothelial dysfunction.⁵⁴ Glutathione peroxidases, particularly GPx1 have also been implicated in the development and prevention of many common and complex diseases, including cancer and cardiovascular disease (Fig. 5).⁵⁵

8. Conclusion

The activities of superoxide dismutase (SOD), catalase(CAT) and glutathione peroxidase (GPX) constitute a first line antioxidant defence system which plays a key and fundamental role in the total defense mechanisms and strategies in biological systems.