The primordial high energy compound: ATP or inorganic pyrophosphate?

The pyrophosphate-dependent phosphofructokinase (PPi-PFK) of Entamoeba histolytica displays a millionfold preference for inorganic pyrophosphate (PP,) over ATP (calculated as the ratio of k(cat)/K-m). The introduction of a single mutation by site-directed mutagenesis changes its preference from PP, to ATP. The single mutant has an 8-fold preference for ATP whereas a related double mutant shows a preference exceeding 10,000-fold. The results suggest the presence of a latent nucleotide binding site aligned for a catalytic role in PPi-PFK. It is proposed that the ancestral PFK was an ATP-dependent enzyme and that PPi-PFKs are a later evolving adaptation.