Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Significance It is still unknown how an early metabolism produced the sugar phosphates central for life. We provide evidence that gluconeogenesis, the anabolic counterpart to glycolysis, could have emerged nonenzymatically. We describe that the gluconeogenic carbon-bond–forming reaction has a nonenzymatic pendant that occurs in ice and that leads to the accumulation of fructose 1,6-bisphosphate as (re-)built from glycolytic catabolites. As a nonenzymatic glycolysis has been described previously, the discovery of this reaction could both help to explain the origin of the larger cellular sugar phosphates and provide a scenario in which an early metabolic system was able to escape equilibrium. The reaction further hints that the earliest anabolic enzymes could have been as simple as single amino acids.