Journal of Energy Bioscience 2025, Vol.16, No.1, 31-41 http://bioscipublisher.com/index.php/jeb 33 3.2 Amino acid and nucleotide synthesis: NADPH in the synthesis of non-essential amino acids and nucleotides NADPH is also indispensable in the synthesis of non-essential amino acids and nucleotides. For example, the synthesis of proline requires NADPH in mitochondria. NAD kinase 2 (NADK2) can generate mitochondrial NADP+. If there is a problem in this process, it will lead to insufficient NADPH in mitochondria, which will affect the production of proline. This shows that mitochondrial NADPH is indispensable in the synthesis of pyrroline-5-carboxylate, an intermediate in the synthesis of proline (Tran et al., 2021). In addition to amino acids, NADPH is also involved in the production of nucleotides. In the pentose phosphate pathway (PPP), NADPH helps synthesize ribose-5-phosphate, a sugar that is a raw material for nucleotides. At the same time, NADPH also provides reducing power (Corpas and Barroso, 2014; Xiao et al., 2018) (Figure 1). Figure 1 Metabolic sources of NADP(H) and the cytosolic/mitochondrial NADPH shuttle (Adopted from Xiao et al., 2018) Image caption: In the cytosol, NADPH is primarily produced by G6PD and 6PGD in the pentose phosphate pathway. ME1 also contributes to cytosolic NADPH production. Mitochondrial NADPH is generated by NADP+-dependent IDH2, GLUD, NNT, and ME3. The cytosolic and mitochondrial NADPH is exchanged through the isocitrate-α-KG shuttle, where cytosolic IDH1 and mitochondrial IDH2 catalyze the interconversion of isocitrate and α-KG in conjunction with the interconversion of NADP+ and NADPH. The citrate carrier protein (encoded by SLC25A1 gene) and the α-KG/malate antiporter (encoded by SLC25A11 gene) mediate the transport of isocitrate and α-KG between cytosol and mitochondria, respectively. 6PG, 6-phosphogluconate; 6PGD, 6-phosphogluconate dehydrogenase; G6P, glucose-6-phosphate; G6PD, glucose-6-phosphate dehydrogenase; NNT, nicotinamide nucleotide transhydrogenase; R5P, ribose-5-phosphate; SCL25A1, solute carrier family 25 member 1 (Adopted from Xiao et al., 2018) 3.3 Secondary metabolite synthesis: importance of NADPH in the synthesis of plant secondary metabolites and pharmaceuticals NADPH is critical for plants to produce certain special compounds, which can often be used as drugs. NADPH provides reducing power to the enzyme reactions that synthesize these molecules. Enzymes such as cytochrome P450 require NADPH to work properly. This enzyme can hydroxylate some substrates, such as flavonoids, alkaloids, terpenes, etc., which are common plant secondary metabolites (Hajeyah et al., 2020). There are also some NADPH-dependent oxidoreductases, such as ferredoxin-NDP reductase and NADP-dependent malic
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