Consequently, prebiotic chemistry may have been fundamentally distinct from the biochemistry observed in extant organisms. While the rTCA cycle offers a plausible route for early autotrophic metabolism, its prebiotic role remains unclear. Previous studies have established its thermodynamic favorability, but understanding the kinetics of its uncatalyzed reactions is crucial for evaluating whether this pathway could have operated prior to the evolution of enzymes, particularly in the presence of competing side reactions. The short-lived nature of intermediates and the large number of potential off-target reactions make experimental mechanistic studies challenging but recently developed computational approaches make it timely to revisit these gaps.