Journal of Energy Bioscience 2025, Vol.16, No.1, 31-41 http://bioscipublisher.com/index.php/jeb 32 about its possible future application in treating diseases. By organizing and analyzing the current research results, we hope to further illustrate the importance of NADPH to cellular health and explore its potential as a therapeutic tool. 2 NADPH and Cellular Metabolism 2.1 Detailed examination of NADPH's generation pathways NADPH is produced by several metabolic pathways in cells, the most important of which is the pentose phosphate pathway (PPP), and some enzymes, such as malic enzyme, can also participate. The oxidation phase of PPP is critical and is mainly completed by two enzymes: glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH). These two enzymes help cells produce NADPH (Corpas et al., 2020; Fuentes-Lemus et al., 2023). In addition to PPP, there are other enzymes that can also produce NADPH, such as NADP-dependent malic enzyme (NADP-ME) and NADP-dependent isocitrate dehydrogenase (NADP-ICDH). These enzymes are distributed in different areas of the cell, such as the cytoplasm, mitochondria and peroxisomes (Corpas and Barroso, 2014; Corpas et al., 2020). It is precisely because of their existence that NADPH can be stably supplied in the cell, which is important for various anabolic and detoxification reactions. 2.2 NADPH's role in maintaining cellular redox balance NADPH is active in many antioxidant systems of the cell, where it is the main reductant and helps the cell maintain a normal redox state. NADPH is important for the action of glutathione reductase, an enzyme that regenerates reduced glutathione (GSH), which is critical for the cell to resist oxidative damage (Lee et al., 2002). NADPH also participates in the ascorbate-glutathione cycle and supports the activity of NADPH oxidase. This oxidase generates reactive oxygen species (ROS), which can be used for cell signaling (Corpas et al., 2020; Fuentes-Lemus et al., 2023). NADPH also contributes to the normal function of thioredoxin reductase, an enzyme that regulates the status of thioredoxin. Thioredoxin itself is also an important antioxidant tool (Corpas et al., 2020). The production and use of NADPH must be balanced to prevent oxidative stress and maintain a stable environment in the cell (Ying, 2008). 2.3 Comparative analysis with other cellular cofactors In cellular metabolism, NADPH, NADH and FADH2 are all very important cofactors, but their respective tasks are different. NADH is mainly involved in catabolism, such as glycolysis and the tricarboxylic acid cycle (TCA), and it can help cells produce ATP through oxidative phosphorylation (Blacker and Duchen, 2016; Xiao et al., 2018). NADPH is more used for anabolism. It can support the synthesis of fatty acids and nucleotides, and also help cells maintain a healthy redox environment (Ying, 2008; Corpas and Barroso, 2014). FADH2 is similar to NADH and also participates in the electron transport chain, which is important for the synthesis of ATP (Xiao et al., 2018). Although both NADH and FADH2 are more inclined to energy generation, the role of NADPH is more focused on making substances needed by cells and protecting cells from oxidation, which also explains its unique position in metabolism (Blacker and Duchen, 2016; Shimizu and Matsuoka, 2019). 3 Biosynthesis Reactions Facilitated by NADPH 3.1 Lipid biosynthesis: role of NADPH in fatty acid and cholesterol biosynthesis NADPH is critical in the process of lipid production, especially in the synthesis of fatty acids and cholesterol. NADP+-dependent isocitrate dehydrogenase (IDPc) in the cytoplasm is an important source of NADPH. It plays an important role in these synthesis reactions. When adipocytes differentiate, the activity of IDPc increases and the expression level also increases. This is closely related to the increase in fat formation. Transgenic experiments conducted on mice found that excessive expression of IDPc can lead to fatty liver, increased blood lipids, and obesity. This shows that it plays an important role in lipid metabolism (Koh et al., 2004). NADPH is also very important for the activity of two key enzymes: fatty acid synthase and HMG-CoA reductase. The former is a key enzyme in fatty acid synthesis, and the latter is involved in cholesterol synthesis (Pollak et al., 2007; Spaans et al., 2015).
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