Free CoA-mediated regulation of intermediary and central metabolism: an hypothesis which accounts for the excretion of alpha-ketoglutarate during aerobic growth of Escherichia coli on acetate.
During growth of Escherichia coli on acetate, phosphotransacetylase and alpha-ketoglutarate dehydrogenase are in direct competition for their common co-factor, HS-CoA. Such competition is resolved in favour of phosphotransacetylase, thus rendering alpha-ketoglutarate dehydrogenase rate-limiting (controlling) and, in turn, creating a bottleneck at the level of alpha-ketoglutarate in the Krebs cycle. Accumulation of alpha-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.
El-Mansi
Mansi
M
School of Life Sciences, Faculty of Health and Life Sciences, Napier University, Edinburgh, EH10 5DT, Scotland, UK.
D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000332:Aerobiosis; D003065:Coenzyme A / Q000378:metabolism*; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007656:Ketoglutaric Acids / Q000378:metabolism*
D000085:Acetates; D007656:Ketoglutaric Acids; D000105:Acetyl Coenzyme A; D003065:Coenzyme A