*5.2.2. Non-enzymatic antioxidants*

ROOH + 2GSH → GSSG + H2 O + ROH. (12)

The fact that GPx also acts on lipid hydroperoxides suggest it may be involved in repairing cellular damages due lipid peroxidation [49]. The activity of GPx is dependent on the constant availability of reduced glutathione which is regenerated from oxidized glutathione (GSSG). **Glutathione reductase** (GRx): GRx is a flavine nucleotide dependent enzyme and has a similar tissue distribution to glutathione peroxidase [49]. The role of GRx is to generate GSH from

. (13)

GSSG using NADPH in order to increase the ratio of reduced to oxidized glutathione:

The NADPH required by this enzyme to replenish the supply of reduced glutathione is provided by Glucose-6-phosphate dehydrogenase (G-6-PD) in the pentose phosphate pathway.

GSSG + NADPH + H+ → 2GSH + NADP<sup>+</sup>

58 Phytochemicals - Source of Antioxidants and Role in Disease Prevention

**Figure 2.** Oxidative stress defence mechanism.

The non-enzymatic antioxidants are usually low-molecular-weight antioxidant (LMWA) compounds capable of preventing oxidative damage either by directly interacting with ROS or indirectly by chelating metals [50]. Transition metals are directly chelated by some of this LMWA thereby preventing them from participating in metal-mediated Haber-Weiss reaction [51]. Other direct acting LMWA molecules scavenge free radicals by donating electrons to free radicals to make them stable thereby preventing attacks of biological targets. These LMWA molecules also called scavengers may be advantageous over enzymatic antioxidants as they can penetrate cellular membranes and be localized in close proximity to the biological target due to their small size. More so, these non-enzymatic antioxidants can interact together to scavenge free radicals and their scavenging activity may be synergic. Most scavengers originate from endogenous sources, such as biosynthetic processes and waste-product generation by the cell. However, the number of LMWA synthesized by the living cell or generated as waste products such as histidine dipeptides, glutathione, uric acid, lipoic acid and bilirubin is limited [52]. More so, the concentration of scavenger must be sufficiently high to compete with the biological target on the deleterious species [50]. As such, exogenous sources of nonenzymatic antioxidants especially from plant diet and phytochemicals are needed to supplement the endogenous non-enzymatic antioxidants. The oxidative stress defense mechanism in humans is summarized in **Figure 2**.
