*4.1.3 Glutathione perioxidases (GPx)*

Glutathione peroxidase (EC 1.11.1.9) contains a single selenocysteine residue in each of the four identical subunits, which is important for enzyme activity. GPx (80 kDa) is an imperative intracellular enzyme that catalyzes H2O2 to water and lipid peroxides to their corresponding alcohols mainly in the mitochondria and sometimes in the cytosol. In mammals, there are five GPx isoenzymes. Though their expression is ubiquitous, the level of each isoform differs depending on their tissue type. Mitochondrial and cytosolic glutathione peroxidase (GPx1 or cGPx) reduces fatty acid hydroperoxides and H2O2 at the expense of glutathione [32].

GPx1 is the main ubiquitous selenoperoxidase present in most cells; found in the cytosolic, mitochondrial, and peroxisomal compartments. It is an important antioxidant enzyme required in the detoxification of H2O2 and lipid hydroperoxides and preventing DNA, protein and lipids damage by harmful accumulation of intracellular H2O2 [33]. GPx1 uses GHS as an obligate co-substrate in the reduction of H2O2 to water [32]. Phospholipid hydroperoxidase glutathione (PHGPX) is found in most tissues and can directly reduce the phospholipid hydroperoxides, fatty acid hydroperoxides, and cholesterol hydroperoxides that are produced in peroxidized membranes and oxidized lipoproteins [30].

GPx4 is found in both the cytosol and the membrane fraction, and is highly expressed in renal epithelial cells and tests. Cytosolic GPx2 or extracellular GPx3 is inadequately found in nearly all tissues except for the gastrointestinal tract and kidney. In recent, GPx5, a new kind, expressed particularly in mouse epididymis, is selenium independent [34].

Several studies underlined the clinical importance of GPx. In addition, GPx, especially GPx1, have been implicated in the progression and prevention of many frequent and complex diseases, including cancer and cardiovascular disease [34, 35].

#### *4.1.3.1 Application*

GPx is an important antioxidant enzyme in the body. Glutathione (GHS), the master antioxidant, is important for GPx levels due to the closely linked relationship; GHS is a tripeptide that protects the cells against the negative effects of pollution and functions as the body's immune system booster. GHS plays an essential role in red blood cells to remain intact and protects white blood cells, which are responsible for the immune system. An antioxidant's role is specifically essential for the brain because it is sensitive to the presence of free radicals. To increase the body's protection from free radicals, it is imperative to combine certain antioxidants such as glutathione, vitamin C and E, Se, and GPx [3].

#### **4.2 Nonenzymatic antioxidants**

In previous decades, there has been increasing evidence that large amounts of antioxidants present in our diet contribute to the antioxidant defense system by preventing oxidative stress and specific human diseases. Phytochemicals, the plant-derived compounds, are one of the classes of the dietary factors, which play an essential role in functions of the body. Food materials contain a number of natural compounds reported to have antioxidant characteristics due to the presence

**11**

*Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

*4.2.1 Glutathione*

*4.2.1.1 Application*

*4.2.2 Vitamin E*

*4.2.2.1 Application*

cal, cardiovascular, and physiological disorders [38].

glutathione transferase (GST) [42, 43].

in the onset of Parkinson's disease [44].

LDL, and prevent ischemic heart disease [49].

of hydroxyl groups in their structure. Synthetic and natural antioxidants prevent the oxidative damage to the most important macromolecules such as lipids, proteins, and nucleic acids found in human body through scavenging the free radicals formed in different biochemical processes [36]. These antioxidants consist of small molecules including vitamin C, E, and β-carotene or natural antioxidants such as flavonoids, tannins, coumarins, phenolics, and terpenoids [37]. Because of oxidative stress, the free radicals that have been produced react with lipids, proteins and nucleic acids and lead to stimulation of apoptosis, which causes various neurologi-

In addition to phytochemical antioxidants, which can protect the body from oxidative damage, there are other antioxidants for example polyphenols, lycopene, and lutein [39]. Even though there has been a considerable concentration on antioxidant function of phytochemicals for several years, it is distinguished that phytochemicals have nonantioxidant effects important for health such as cell signaling and gene expression [40].

Glutathione (γ-glutamyl-cysteinyl-glycine; GSH) is a tripeptide and is the most abundant intracellular antioxidant protecting normal cells from oxidative injury due to its role as a substrate of ROS scavenging enzymes. Glutathione is primarily present in its reduced form (GSH) in normal conditions, with only a small amount being found in the fully oxidized state (GSSG) [41]. Glutathione functions as a nonenzymatic antioxidant through free radical scavenging in cells and serves as a cofactor for several enzymes, include GPx, glutathione reductase (GR), and

Recently, there is a new era of therapeutic applications of glutathione through the association of decreased GSH levels with the common features of aging and a wide range of pathological conditions, including neurodegenerative disorders. Remarkably, depletion and alterations of GSH in its metabolism appear to be crucial

Vitamin E, C, and β-carotene are the main antioxidant vitamins for tissues against free radical damage. Vitamin E, a major lipid soluble antioxidant, functions as the most important membrane-bound antioxidant, neutralizing free radicals, and preventing oxidation of lipids within membranes [45]. Vitamin E is the free radical scavenger in the prevention of chronic diseases [46]. α-Tocopherol is the main form of vitamin E with antioxidant and immune functions. α-tocopherol has been revealed to be a more effective inhibitor of peroxynitrite-induced lipid peroxidation and inflammatory reactions [47]. *In vitro* tocotrienols have excellent antioxidant activity and have been proposed to restrain ROS more effectively than tocopherols [48].

The main function of vitamin E is to protect against lipid peroxidation through evidence suggesting that α-tocopherol and vitamin C function together in a cyclic type of process. It has been reported that vitamin E supplementation in hypercholesterolemic patients has shown to increase autoantibody levels against oxidized

#### *Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

of hydroxyl groups in their structure. Synthetic and natural antioxidants prevent the oxidative damage to the most important macromolecules such as lipids, proteins, and nucleic acids found in human body through scavenging the free radicals formed in different biochemical processes [36]. These antioxidants consist of small molecules including vitamin C, E, and β-carotene or natural antioxidants such as flavonoids, tannins, coumarins, phenolics, and terpenoids [37]. Because of oxidative stress, the free radicals that have been produced react with lipids, proteins and nucleic acids and lead to stimulation of apoptosis, which causes various neurological, cardiovascular, and physiological disorders [38].

In addition to phytochemical antioxidants, which can protect the body from oxidative damage, there are other antioxidants for example polyphenols, lycopene, and lutein [39]. Even though there has been a considerable concentration on antioxidant function of phytochemicals for several years, it is distinguished that phytochemicals have nonantioxidant effects important for health such as cell signaling and gene expression [40].
