Journal of Energy Bioscience 2025, Vol.16, No.1, 31-41 http://bioscipublisher.com/index.php/jeb 34 enzyme, which also help maintain NADPH levels in cells. The activity of these enzymes can further promote the synthesis of various important metabolites (Corpas et al., 2020). NADPH is not only useful in basic metabolism, but also very important in these more complex secondary metabolic pathways. It helps synthesize many biologically active substances, such as plant medicinal ingredients (Takayanagi et al., 1980; Blacker et al., 2014). 4 NADPH in Antioxidant Defense Mechanisms 4.1 Overview of oxidative stress and the necessity of antioxidants in cellular protection Oxidative stress occurs because there are too many reactive oxygen species (ROS) and the cells are not able to remove these harmful molecules. ROS include free radicals and peroxides, which are byproducts of normal cell metabolism, especially aerobic respiration. If too much ROS is produced, it will damage the DNA, proteins and fats in the cell. This will impair cell function and even cause cell death. In order to cope with this stress, cells have developed many antioxidant systems. These systems include enzymes and non-enzymatic antioxidants, which together help cells maintain redox balance and prevent damage (Benhar, 2018; Hasan et al., 2022; Chai and Mieyal, 2023). 4.2 Glutathione redox cycle: NADPH's role in regenerating reduced glutathione The glutathione (GSH) redox cycle is an important antioxidant mechanism in cells. GSH is a common non-enzymatic antioxidant that can directly remove ROS. In this process, GSH will become oxidized GSSG. At this time, the cell needs to use NADPH and glutathione reductase to convert GSSG back to GSH. This process is particularly critical for maintaining the redox balance of cells and can also help cells fight oxidative stress. The GSH/Grx system can also regulate the S-glutathionylation reaction of proteins. This process is reversible and also requires the participation of NADPH. It is very helpful in maintaining the signal transduction and red oxygen status of cells (Bradshaw, 2019; Ferguson and Bridge, 2019; Chai and Mieyal, 2023). 4.3 Thioredoxin system: function of NADPH in the thioredoxin system and its significance in DNA repair The thioredoxin (Trx) system is another important antioxidant system. It consists of Trx, Trx reductase (TrxR) and NADPH. The role of Trx is to help proteins restore their structure, and it can reduce disulfide bonds in proteins. The function of TrxR is to use NADPH to reduce oxidized Trx. This process not only helps proteins maintain function, but is also closely related to DNA repair. Because many proteins involved in DNA synthesis and repair also need to maintain the correct redox state. This Trx/TrxR system also plays a role in cell proliferation and survival, so it is very important for the entire cell homeostasis (Benhar, 2018; Ferguson and Bridge, 2019; Hasan et al., 2022). 4.4 Antioxidant enzymes: interaction of NADPH with enzymes like catalase and superoxide dismutase in reducing oxidative damage NADPH is also involved in supporting the function of several antioxidant enzymes, such as catalase and superoxide dismutase (SOD). Catalase can break down harmful hydrogen peroxide into water and oxygen, while SOD can turn superoxide free radicals into less dangerous substances. These enzymes will be oxidized after working, and NADPH can provide reducing power to restore them to a state where they can continue to work, so that they can continue to work and protect cells from oxidative damage (Figure 2). NADPH is also involved in the ascorbic acid-glutathione cycle and the NADPH-dependent thioredoxin system. This once again illustrates the central position of NADPH in the cellular antioxidant system (Ryoo and Kwak, 2018; Corpas et al., 2020; Liu et al., 2020). 5 Regulation of NADPH Homeostasis 5.1 Mechanisms that cells employ to regulate NADPH levels Cells control NADPH levels in a variety of ways to maintain a balance between its production and use. NADPH is primarily generated through the pentose phosphate pathway (PPP). This pathway is regulated by glucose-6-phosphate dehydrogenase (G6PD) and AMP kinase (Tao et al., 2017). Another way is through NAD+ kinases in the cytoplasm and mitochondria, which convert NAD+ to NADP+ and then reduce it to NADPH (Bradshaw, 2019). Cells store NADPH in different areas, such as in the cytoplasm and mitochondria, which helps
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