Author summary Redox reactions define the energetic constraints within which life can exist. However, measurements of reduction potentials are scarce and unstandardized, and current prediction methods fall short of desired accuracy and coverage. Here, we harness quantum chemistry tools to enable the high-throughput prediction of reduction potentials with unparalleled accuracy. We calculate the reduction potentials of all redox pairs that can be generated using known biochemical compounds. This high-resolution dataset enables us to uncover global trends in metabolism, including the differences between and within oxidoreductase groups. We further demonstrate that the redox potential of NAD(P) optimally satisfies two constraints: reversibly reducing and oxidizing the vast majority of redox reactions in central metabolism while keeping the concentration of reactive carbonyl intermediates in check.