ArticleJACS Au2026
Progress toward a Nonenzymatic Gluconeogenesis: One-Pot Reactions and Model Systems.
Article in JACS Au, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
The earliest cells that can be reconstructed by phylogenetics built their sugars from ketoacids using gluconeogenesis. Metabolic theories for the origin of life suggest that metabolic pathways, including gluconeogenesis, are remnants of a process that started nonenzymatically. However, what conditions might have allowed a nonenzymatic gluconeogenesis to occur remain unclear. Here, we explore the influence of metals and pH on nonenzymatic versions of the reactions of gluconeogenesis. One-pot conditions were developed for the nonenzymatic conversion of phosphoenolpyruvate to 3-phosphoglycerate and for the conversion of fructose-1,6-bisphosphate to glucose-6-phosphate. Proof-of-concept conditions for the conversion of acyl phosphates to thioesters and their subsequent reduction to aldehydes, a reaction sequence seen in the conversion of 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate, were developed on model compounds. Our findings suggest that an environment capable of initiating a nonenzymatic gluconeogenesis would have needed simultaneous acid and base catalysis, pointing beyond chemistry in bulk solution.
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