Journal of Energy Bioscience 2025, Vol.16, No.5, 227-237 http://bioscipublisher.com/index.php/jeb 230 3.3 Redox homeostasis PPP continuously generates NADPH, which is a key pathway for cells to maintain REDOX balance. NADPH can not only reduce oxidized glutathione (GSSG) to reduced glutathione (GSH) to protect cells from damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS), but also regulate signaling pathways related to oxidative stress (Stincone et al., 2014; Chen et al., 2019; Cherkas et al., 2019; Ge et al., 2020; Masi et al., 2021; TeSlaa et al., 2023; Fuentes-Lemus et al., 2023; Qiao et al., 2025). During acute oxidative stress, cells rapidly shift glucose metabolism to PPP to quickly replenish NADPH and preferentially support the antioxidant system. The activity of PPP-related enzymes is regulated by oxidative modification. If these enzymes are damaged, NADPH production decreases and cells are more prone to oxidative damage. Furthermore, the dynamic regulation of PPP can also participate in a broader antioxidant response by influencing gene expression and signal transduction (Kruger et al., 2011). 4 Biosynthetic Role of the PPP 4.1 Nucleotide biosynthesis The non-oxidizing branch of the pentose phosphate pathway (PPP) can generate ribose 5-phosphate (R5P). It is the direct raw material for the synthesis of nucleotides and nucleic acids. R5P is not only used in the synthesis of DNA and RNA, but also provides key substances during cell division and repair. PPP can be regulated as needed and can efficiently supply pentose sugars required for nucleotide synthesis during rapid cell proliferation or tumor growth (Stincone et al., 2014; Ge et al., 2020; Polat et al., 2021; TeSlaa et al., 2023; Qiao et al., 2025). 4.2 Amino acid metabolism PPP can provide a variety of precursors for amino acid synthesis. For instance, its intermediate product, erythrito-4-phosphate (E4P), is an important substrate for the synthesis of aromatic amino acids (phenylalanine, tyrosine and tryptophan). PPP also indirectly regulates the synthesis of non-essential amino acids by influencing the direction of carbon flow and the supply of NADPH, and maintains the balance of the entire amino acid metabolic network (Bertels et al., 2021; Gupta and Gupta, 2021; Rashida and Laxman, 2021; Srivastava, 2024). 4.3 Lipid biosynthesis The NADPH generated by PPP provides reducing power for the synthesis of lipids such as fatty acids, cholesterol and phospholipids. NADPH is a necessary coenzyme for fatty acid synthase and enzymes related to cholesterol synthesis. In tissues where lipid synthesis is active, such as the liver, adipose tissue and tumor cells, the activity of PPP is significantly enhanced. In addition, phospholipid synthesis is also related to nucleotide metabolism and NADPH generation, which further indicates that PPP is in a core position in lipid metabolism (Wasylenko et al., 2015; Gupta and Gupta, 2021; TeSlaa et al., 2023; Zhu et al., 2024). 4.4 Other anabolic processes PPP also provides raw materials and reducing power for other anabolic processes, such as the synthesis of vitamins, coenzymes and cell wall components (such as lipopolysaccharides). Some intermediate products of PPP can also act as signaling molecules to regulate cell growth, differentiation and stress response. PPP exhibits diverse functions in plant, microbial and animal cells, indicating that it is an important hub in cellular anabolic metabolism (Rahman andHasan, 2014; Stincone et al., 2014; Sharkey, 2021; Srivastava, 2024). 5 Regulatory Mechanisms 5.1 Enzymatic control The key enzymes of the pentose phosphate pathway (PPP) are mainly controlled through allosteric regulation and feedback inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of PPP. Its activity is affected by NADP+ and NADPH. NADP+ can activate it, while NADPH will inhibit it. In this way, NADPH forms a negative feedback to G6PD, thereby maintaining the balance of carbon flow in a steady state (Ramos-Martinez, 2017; TeSlaa et al., 2023). When cells are under oxidative stress, NADPH consumption accelerates, inhibition is lifted, and the flux of PPP will increase rapidly to replenish the reducing power (Christodoulou et al., 2018). In addition, enzymes in glycolysis, such as phosphoglucose isomerase (PGI) and
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