Journal of Energy Bioscience 2025, Vol.16, No.5, 227-237 http://bioscipublisher.com/index.php/jeb 227 Research Insight Open Access The Energy Metabolic Function and Biosynthetic Role of the Pentose Phosphate Pathway Xinyi Fang, Gang Xu Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, China Corresponding email: xinyi.fang@jicat.org Journal of Energy Bioscience, 2025, Vol.16, No.5 doi: 10.5376/jeb.2025.16.0022 Received: 27 Jul., 2025 Accepted: 03 Sep., 2025 Published: 17 Sep., 2025 Copyright © 2025 Fang and Xu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Fang X.Y., and Xu G., 2025, The energy metabolic function and biosynthetic role of the pentose phosphate pathway, Journal of Energy Bioscience, 16(5): 227-237 (doi: 10.5376/jeb.2025.16.0022) Abstract The pentose phosphate pathway (PPP) is an important branch in cellular metabolism. It is not only related to energy metabolism but also responsible for biosynthesis. PPP has two parts. Oxidative branches can produce NADPH, which is used to maintain the REDOX balance within cells. It can also support the synthesis of fatty acids and cholesterol, and help cells resist oxidative stress. Non-oxidizing branches provide some raw materials, such as ribo5-phosphoric acid, for the synthesis of nucleotides and amino acids. PPP is closely related to pathways such as glycolysis and the tricarboxylic acid cycle. They will cooperate with each other and adjust at any time to meet the needs of cells in different situations. In recent years, studies have found that PPP is often abnormally regulated in diseases such as tumors and diabetes. Meanwhile, it also has great application value in the field of biotechnology. This article mainly reviews the role of PPP in energy metabolism and biosynthesis, and points out its significant importance in health, disease and bioengineering. Finally, we also put forward a goal: in the future, we will regulate PPP more precisely through systems biology and new technologies. Further in-depth research on the regulatory mechanism of PPP may provide new ideas for disease treatment and industrial production. Keywords Pentose phosphate pathway; Energy metabolism; Biosynthesis; NADPH; REDOX steady state 1 Introduction The Pentose Phosphate Pathway (PPP) is an important branch in the cellular metabolic network. It is on par with glycolysis and the tricarboxylic acid cycle, and is also one of the earliest discovered metabolic pathways. PPP plays a significant role in maintaining carbon balance, providing raw materials for nucleotide and amino acid synthesis, offering reducing power (NADPH) for synthesis reactions, and helping cells resist oxidative stress. Meanwhile, it is also closely related to the growth, differentiation, aging of cells, as well as the occurrence of some diseases (such as cancer, diabetes, etc.) (Kruger and Von Schaewen, 2003; Stincone et al., 2014; Ge et al., 2020; Gupta and Gupta, 2021; Rashida and Laxman, 2021; TeSlaa et al., 2023). PPP consists of two parts: oxidized branches and non-oxidized branches. The oxidation branch mainly generates NADPH and ribose 5-phosphate. The non-oxidative branch provides different synthetic raw materials for cells through the transformation between sugar and phosphate, and is closely associated with other metabolic pathways such as glycolysis (Bertels et al., 2021; Sharkey, 2021). The generation of NADPH not only supports the synthesis of fatty acids, cholesterol and deoxynucleotides, etc., but also helps maintain the REDOX balance of cells and participates in antioxidant protection and signal regulation (Chen et al., 2019; Fuentes-Lemus et al., 2023; TeSlaa et al., 2023). The intermediate products generated by PPP can also be used as raw materials to synthesize biological macromolecules such as nucleic acids, amino acids and vitamins (Stincone et al., 2014; Bertels et al., 2021; Gupta and Gupta, 2021). In addition, PPP has dynamic regulation in different environments, and this regulation is crucial for maintaining metabolic homeostasis and cellular adaptation to external changes (Masi et al., 2021; Rashida and Laxman, 2021). The purpose of this study is to systematically organize the functions of the pentose phosphate pathway in energy metabolism and biosynthesis, with a focus on its regulatory modalities under different physiological and pathological conditions, as well as its connections with other metabolic pathways. Specific goals include
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