Coordinated Slowing of Metabolism in Enteric Bacteria under Nitrogen Limitation: A Perspective

It is natural to ask how bacteria coordinate metabolism when depletion of an essential nutrient limits their growth, and they must slow their entire rate of biosynthesis. A major nutrient with a fluctuating abundance is nitrogen. The growth rate of enteric bacteria under nitrogen-limiting conditions is known to correlate with the internal concentration of free glutamine, the glutamine pool. Here we compare the patterns of utilization of L-glutamine and L-glutamate, the two central intermediates of nitrogen metabolism. Monomeric precursors of all of the cell's macromolecules -- proteins, nucleic acids, and surface polymers -- require the amide group of glutamine at the first dedicated step of biosynthesis. This is the case even though only a minority (~12%) of total cell nitrogen derives from glutamine. In contrast, the amino group of glutamate, which provides the remainder of cell nitrogen, is generally required late in biosynthetic pathways, e.g. in transaminase reactions for amino acid synthesis. We propose that the pattern of glutamine dependence coordinates the decrease in biosynthesis under conditions of nitrogen limitation. Hence, the glutamine pool plays a global regulatory role in the cell.