Molecules 2026, 31(2), 242; https://doi.org/10.3390/molecules31020242 (registering DOI) - 11 Jan 2026
Abstract
The concept of energy-rich molecules is central to metabolic activity and the coupling of catabolic and anabolic processes. Here, we use the term “energy-rich” only in the (bio)chemical sense, i.e., for molecules containing particularly weak bonds that when exchanged for stronger bonds results
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The concept of energy-rich molecules is central to metabolic activity and the coupling of catabolic and anabolic processes. Here, we use the term “energy-rich” only in the (bio)chemical sense, i.e., for molecules containing particularly weak bonds that when exchanged for stronger bonds results in a release of energy (generally ≥ 20 kJ mol−1). The typical energy-rich molecules are nucleoside triphosphates (NTPs), thioesters, and dioxygen. It must be emphasized that the number of bonds is conserved in biochemical reactions, so that the difference in free energy between substrates and products only depends on the difference in bond energies. It is evident that using the term “energy-rich” for molecules with weak bonds is subject to misinterpretation. Therefore, some authors suggested to replace this term by molecule of high group transfer potential. This is justified for NTPs and thioesters, which have a high transfer potential for, respectively, phosphoryl or acyl groups, but not for dioxygen. Therefore, the concepts of energy-richness and group transfer potential should be treated as different and only be used within specific contexts. We discuss how these two notions can be used to understand the coupling mechanisms in biochemical processes as well as the interplay between thioesters, redox coupling, and phosphate transfer reactions.
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(This article belongs to the Section Chemical Biology)
