α-ketoglutarate coordinates carbon and nitrogen utilization via Enzyme I inhibition

Microbes survive in a variety of nutrient environments by modulating their intracellular metabolism. Balanced growth requires coordinated uptake of carbon and nitrogen, the primary substrates for biomass production. The mechanisms that balance carbon and nitrogen uptake are, however, poorly understood. We find in Escherichia coli that a sudden increase in nitrogen availability results in an almost immediate increase in glucose uptake. The concentrations of known glycolytic intermediates and regulators, however, remain homeostatic. Instead, we find that α-ketoglutarate, which accumulates in nitrogen limitation, directly blocks glucose uptake by inhibiting Enzyme I, the first step of the phosphotransferase system (PTS). This enables rapid modulation of glycolytic flux without marked concentration changes in glycolytic intermediates by simultaneously accelerating glucose import and consumption of the terminal glycolytic intermediate phosphoenolpyruvate. Quantitative modeling shows that this previously unidentified regulatory connection is in principle sufficient to coordinate carbon and nitrogen utilization.

• Publication year

  2011

• Venue

  Nature Chemical Biology

• Publication date

  2011-09-01

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1038/nchembio.685PMID 22002719PMCID 3218208
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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