The BRENDA database was mined for all reports of small molecule regulatory interactions across all species. These interactions were aggregated by unique metabolite-reaction pairs. For each interaction evident in at least 10 different organisms and supported by evidence from at least 10 different published studies, followed by manual curation of the results. We identified the broad phylogenetic taxon within which the interaction was present. Nearly all conserved interactions are inhibitory, with a two exceptions: the activation of PFK by three metabolites, AMP, ADP, and fructose-2,6-bisphosphate, and the activation of PEP carboxylase by G6P. 16