Hidden biochemical fossils reveal an evolutionary trajectory for glycolysis in the prebiotic era.

Glycolysis is present in nearly all organisms alive today. This article proposes an evolutionary trajectory for the development of glycolysis in the framework of the chemoautotrophic theory for the origin of life. In the proposal, trioses and triose-phosphates were appointed to starting points. The six-carbon and the three-carbon intermediates developed in the direction of gluconeogenesis and glycolysis, respectively, differing from the from-bottom-to-up development of enzymatic glycolysis. The examination of enzymatic reaction mechanisms revealed that the enzymes incorporated chemical mechanisms of the nonenzymatic stage, making possible to identify kinship between glyoxalases and glyceraldehyde 3-phosphate dehydrogenase as well as methylglyoxal synthase and triose-phosphate isomerase. This developmental trajectory may shed light on how glycolysis might have developed in the nonenzymatic era.