Glycolytic strategy as a tradeoff between energy yield and protein cost

TLDR

While glycolysis is often portrayed as a single conserved pathway, prokaryotes exhibit diverse routes, notably the Entner–Doudoroff pathway that yields only one ATP per glucose, half the amount produced by the canonical EMP pathway. The study proposes that this diversity reflects a tradeoff between ATP yield and the enzymatic protein required to sustain pathway flux. Using thermodynamic and kinetic analyses, the authors show that the ED pathway requires several‑fold less protein to achieve the same glucose conversion rate as EMP, and genomic data reveal that prokaryotes select pathways based on their energy supply. Energy‑deprived anaerobes preferentially use the high‑ATP EMP pathway, whereas facultative anaerobes and aerobes favor the protein‑efficient ED pathway, linking environmental energy availability to metabolic strategy.

Abstract

Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains of life, not all sugar-consuming organisms use the canonical Embden–Meyerhoff–Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative glycolytic pathways, the most common of which is the Entner–Doudoroff (ED) pathway. The prevalence of the ED pathway is puzzling as it produces only one ATP per glucose—half as much as the EMP pathway. We argue that the diversity of prokaryotic glucose metabolism may reflect a tradeoff between a pathway’s energy (ATP) yield and the amount of enzymatic protein required to catalyze pathway flux. We introduce methods for analyzing pathways in terms of thermodynamics and kinetics and show that the ED pathway is expected to require several-fold less enzymatic protein to achieve the same glucose conversion rate as the EMP pathway. Through genomic analysis, we further show that prokaryotes use different glycolytic pathways depending on their energy supply. Specifically, energy-deprived anaerobes overwhelmingly rely upon the higher ATP yield of the EMP pathway, whereas the ED pathway is common among facultative anaerobes and even more common among aerobes. In addition to demonstrating how protein costs can explain the use of alternative metabolic strategies, this study illustrates a direct connection between an organism’s environment and the thermodynamic and biochemical properties of the metabolic pathways it employs.