Relation of growth and protein synthesis to the adenylate energy charge in an adenine-requiring mutant of Escherichia coli.

When Escherichia coli K-12 strain PC 0294, which is unable to synthesize adenine nucleotides, thereonine, proline, and leucine, was starved for adenine, the concentrations of ATP, ADP, and AMP fell rapidly. The adenylate energy charge was not affected until the adenine nucleotide pool fell to about 30% of its normal value. Similarly, cells in an adenine-limited chemostat grew at intracellular adenine nucleotide pool values as low as 30% of normal, but the energy charge in all cases was approximately 0.90. Incorporation of [14C]leucine into protein in adenine-starved cells continued rapidly as long as the energy charge was in or near its normal range, even when the concentration of ATP was 30% to 10% of its normal value. When glucose was added to cells that had been resuspended in medium lacking both glucose and adenine, the energy charge rose rapidly but the concentration of ATP fell, presumably because of nucleic acid synthesis. The rate of [14C]leucine incorporation into protein rose rapidly while adenine nucleotide concentrations fell, and then declined roughly in parallel with the energy charge. At a given value of energy and of total concentration of adenine nucleotides, the rate of protein synthesis may, of course, vary with the concentrations of precursors and modifiers; thus, the rate cannot be predicted from knowledge only of the energy charge. Our results suggest, however, that the rate of protein synthesis and the capacity for growth are much more sensitive to changes in the value of the energy charge than to changes in the concentration of ATP. Growth occurs when the ATP concentration is reduced to one-third of its normal value, but has not been observed when the energy charge has fallen by as much as 10%.