  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.
