Abstract

In a universe being dragged into disorder by the second law of thermodynamics, living cells must expend energy to maintain their complex organization. In addition to providing a carbon source for biosynthesis, the classical Embden–Meyerhof–Parnas (EMP) and Entner-Doudoroff (ED) pathways help to satisfy this energetic demand by generating ATP during glucose metabolism (1). Based on simple stoichiometry of reactants and products, the EMP pathway appears, at first blush, greatly preferable to the ED pathway, yielding twice as much ATP per glucose. If glucose breakdown and energy conservation are tightly coupled, why is the less-efficient ED pathway so prevalent? What has kept prokaryotic life in its entirety from casting off the ED pathway in favor of the more profitable EMP pathway? In PNAS, Flamholz et al. (2) address these questions by drawing on thermodynamics, enzyme kinetics, mathematical optimization, and genomics.

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