α-ketoglutarate coordinates carbon and nitrogen utilization via enzyme i inhibition

Christopher D. Doucette, David J. Schwab, Ned S. Wingreen, Joshua D. Rabinowitz

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

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. Yet the mechanisms that balance carbon and nitrogen uptake are 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 glycolytic intermediates and known regulators, however, remain homeostatic. Instead, we find that ±-ketoglutarate, which accumulates in nitrogen limitation, directly blocks glucose uptake by inhibiting enzyme I, the first step of the sugarĝ€"phosphoenolpyruvate phosphotransferase system (PTS). This inhibition enables rapid modulation of glycolytic flux without marked changes in the concentrations of glycolytic intermediates by simultaneously altering import of glucose 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.

Original languageEnglish (US)
Pages (from-to)894-901
Number of pages8
JournalNature Chemical Biology
Volume7
Issue number12
DOIs
StatePublished - Dec 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'α-ketoglutarate coordinates carbon and nitrogen utilization via enzyme i inhibition'. Together they form a unique fingerprint.

  • Cite this