title: Control of carbon flux through enzymes of central and intermediary metabolism during growth of Escherichia coli on acetate.
abstract: During aerobic growth of Escherichia coli on acetate, the component parts of the 'acetate switch' are turned-on as a consequence of direct competition, on the one hand, between phosphotransacetylase (PTA) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) for their common co-factor free-CoA (HS-CoA) and, on the other hand, between isocitrate lyase (ICL) and isocitrate dehydrogenase (ICDH) for their common substrate isocitrate. Flux analysis revealed that competitions at both junctions in central metabolism are resolved in a precise way, so that the fraction of HS-CoA flux processed through PTA for biosynthesis relative to that processed through alpha-KGDH for energy generation, matches that observed for isocitrate flux through ICL relative to ICDH at the junction of isocitrate. Whereas the mechanism involved in the partition of carbon flux at the level of HS-CoA in central metabolism remains to be unravelled, the competition at the junction of isocitrate is resolved by the reversible phosphorylation/inactivation of ICDH and the operation of the glyoxylate bypass, the expression of which is subject to regulation at the transcriptional and translational levels as well as being dependent on growth rate.
authors.affiliation: School of Life Sciences, Faculty of Health and Life Sciences, Napier University, Edinburgh, EH10 5DT, Scotland, UK. m.el-mansi@napier.ac.uk
authors.forename: Mansi
authors.initials: M
authors.lastname: El-Mansi
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Cozzone
authors.forename: Joseph
authors.initials: J
authors.lastname: Shiloach
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Eikmanns
mesh_terms: D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D002244:Carbon / Q000378:metabolism*; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D006038:Glyoxylates; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007522:Isocitrate Lyase / Q000378:metabolism; D007523:Isocitrates / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D010709:Phosphate Acetyltransferase / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D000085:Acetates; D003470:Culture Media; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D006038:Glyoxylates; D007523:Isocitrates; D000105:Acetyl Coenzyme A; D002244:Carbon; C034219:isocitric acid; D007521:Isocitrate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D010709:Phosphate Acetyltransferase; D007522:Isocitrate Lyase; C031150:glyoxylic acid