Sugars to Acids via Thioesters: A Computational Study

Extant core metabolic cycles such as the TCA cycle and its related analog pathways utilize carboxylic acids as metabolites, with thioesters playing a key role. We examine if sugars from the potentially autocatalytic formose reaction can be converted to carboxylic acids in the absence of enzymes by calculating the thermodynamics and kinetics of such pathways. We zero in on a mechanism involving the addition of a thiol to an aldehyde, followed by intramolecular disproportionation to form a thioester that can be hydrolyzed into its carboxylic acid. This route is thermodynamically favorable but can have kinetic bottlenecks. We find that elimination of H₂O or H₂S is often the rate-determining step, and that alpha di-carbonyl reactants that do not require such a step are more feasible in the absence of catalysts.