Metabolic alterations mediated by 2-ketobutyrate in Escherichia coli K12.
We have previously proposed that 2-ketobutyrate is an alarmone in Escherichia coli. Circumstantial evidence suggested that the target of 2-ketobutyrate was the phosphoenol pyruvate: glycose phosphotransferase system (PTS). We demonstrate here that the phosphorylated metabolites of the glycolytic pathway experience a dramatic downshift upon addition of 2-ketobutyrate (or its analogues). In particular, fructose-1,6-diphosphate, glucose-6-phosphate, fructose-6-phosphate and acetyl-CoA concentrations drop by a factor of 10, 3, 4, and 5 respectively. This result is consistent with (i) an inhibition of the PTS by 2-ketobutyrate, (ii) a control of metabolism by fructose-1,6-diphosphate. Since fructose-1,6-diphosphate is an activator of phosphoenol pyruvate carboxylase and of pyruvate kinase, the concentration of their common substrate, phosphoenol pyruvate, does not decrease in parallel.
D002087:Butyrates / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007700:Kinetics; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D012265:Ribonucleotides / Q000302:isolation & purification; D013329:Structure-Activity Relationship
D002087:Butyrates; D012265:Ribonucleotides; C005087:alpha-ketobutyric acid; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System