Journal of Energy Bioscience 2025, Vol.16, No.5, 227-237 http://bioscipublisher.com/index.php/jeb 228 summarizing the role of PPP in energy metabolism and its interrelationship with pathways such as glycolysis and fatty acid metabolism; Explain the core role of PPP in biosynthesis, especially the generation of NADPH and ribose 5-phosphate and their subsequent reactions; Explore the connection between abnormal PPP function and the occurrence of diseases; And introduce the new progress in PPP regulation, metabolic engineering and biomedical applications in recent years. This review aims to provide theoretical support for a better understanding of the metabolic function and biosynthetic role of PPP, and also offer references for disease prevention and treatment as well as the improvement of metabolic engineering. 2 Overview of the Pentose Phosphate Pathway 2.1 Pathway structure The pentose phosphate pathway (PPP) is an important branch of glucose metabolism in cells. It is divided into two parts: the oxidation branch and the non-oxidation branch. The oxidation branch starts with glucose-6-phosphate and undergoes a series of irreversible reactions to produce NADPH and ribose 5-phosphate. NADPH provides reducing power for cells, while ribose 5-phosphate is the raw material for synthesizing nucleotides (Alfarouk et al., 2020; Ge et al., 2020; Bertels et al., 2021; Sharkey, 2021). The non-oxidizing branch is composed of reversible reactions catalyzed by transketoolase and transaldoolase. It can convert pentose phosphates (such as ribose 5-phosphate, xylose 5-phosphate) into intermediate substances in glycolysis, such as fructose-6-phosphate and glyceraldehyde 3-phosphate, thereby interlinking with glycolysis. These two branches not only meet the cells' demands for reducing power and synthetic raw materials, but also flexibly regulate the flow direction of carbon by sharing intermediates with glycolysis to adapt to different physiological states. 2.2 Comparison with glycolysis Both the Glycolysis and pentose phosphate pathways start with glucose-6-phosphate, but their products and functions are different. Glycolysis breaks down glucose into pyruvate and generates ATP and NADH for direct energy supply (Ge et al., 2020; Bertels et al., 2021). PPP does not produce ATP but generates NADPH and pentose sugar (Alfarouk et al., 2020; Ge et al., 2020) (Figure 1). There are intermediates between the two that can be converted into each other, such as glucose-6-phosphate, fructose-6-phosphate and glyceraldehyde 3-phosphate. The non-oxidizing branch of PPP can also convert pentose sugar back to these substances, thereby achieving dynamic regulation of carbon flow (Sharkey, 2021). Functionally, glycolysis mainly provides energy; PPP focuses more on providing NADPH and the raw materials required for the synthesis of nucleotides, amino acids, fatty acids, etc. It is particularly important during antioxidant stress and rapid cell division. In addition, the key enzymes of these two pathways are regulated by different metabolic signals, and cells allocate carbon flows according to energy, reducing power and synthetic requirements. 3 Energy Metabolic Function of the PPP 3.1 NADPH production The core function of the pentose phosphate pathway (PPP) is to generate NADPH in the oxidation branch. Under the action of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGDH), after two oxidation reactions, for each molecule of glucose-6-phosphate decomposed, two molecules of NADPH are obtained (Stincone et al., 2014; Chen et al., 2019; Ge et al., 2020; Bertels et al., 2021; Masi et al., 2021; Fuentes-Lemus et al., 2023; TeSlaa et al., 2023). NADPH is the main source of reducing power in cells. It participates in the synthesis of fatty acids, cholesterol, deoxynucleotides, etc., and also provides electrons for antioxidant systems such as glutathione reductase, helping to maintain the REDOX balance of cells (Cherkas et al., 2019; Qiao et al., 2025). Under conditions such as oxidative stress, rapid cell division or immune response, NADPH generated by PPP is particularly important for cells. 3.2 ATP linkages Unlike glycolysis and the tricarboxylic acid cycle, PPP itself does not directly produce ATP. However, PPP and glycolysis share some intermediate products, such as fructose-6-phosphate and glyceraldehyde 3-phosphate. The intercommunication of these substances enables the carbon flow to be dynamically adjusted, thereby indirectly
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