Nonenzymatic Metabolic Reactions and Life's Origins

Prebiotic chemistry aims to explain how the biochemistry of life as we know it came to be. Most efforts in this area have focused on provisioning compounds of importance to life by multistep synthetic routes that do not resemble biochemistry. However, gaining insight into why core metabolism uses the molecules, reactions, pathways, and overall organization that it does requires us to consider molecules not only as synthetic end goals. Equally important are the dynamic processes that build them up and break them down. This perspective has led many researchers to the hypothesis that the first stage of the origin of life began with the onset of a primitive nonenzymatic version of metabolism, initially catalyzed by naturally occurring minerals and metal ions. This view of life's origins has come to be known as metabolism first. Continuity with modern metabolism would require a primitive version of metabolism to build and break down ketoacids, sugars, amino acids, and ribonucleotides in much the same way as the pathways that do it today. This review discusses metabolic pathways of relevance to the origin of life in a manner accessible to chemists, and summarizes experiments suggesting several pathways might have their roots in prebiotic chemistry. Finally, key remaining milestones for the protometabolic hypothesis are highlighted.