Edinburgh Napier University

  During growth of Escherichia coli on acetate, phosphotransacetylase and -ketoglutarate dehydrogenase are in direct competition for their common co-factor, HS-CoA. Such competition is resolved in favour of phosphotransacetylase, thus rendering -ketoglutarate dehydrogenase rate-limiting (controlling) and, in turn, creating a bottleneck at the level of -ketoglutarate in the Krebs cycle. Accumulation of -ketoglutarate is then balanced by its excretion. Addition of pyruvate, glucose or any glycolytic intermediate to acetate-grown culture relieves such a bottleneck by reversing carbon flow through phosphotransacetylase to give acetyl phosphate and much-needed HS-CoA. The urgent need for HS-CoA by the primordial organism might therefore have provided the selective pressure that led to the co-evolution of phosphotransacetylase and the two-malate synthase isoenzymes.