Synthesis and inactivation of aminoacyl-transfer RNA synthetases during growth of Escherichia coli

A method has been developed to measure the rates of synthesis and of degradation of bacterial enzymes during growth by means of density labeling with deuterium to distinguish pre-existing from newly-made molecules. Use of this method has led to the discovery that some of the aminoacyl-transferRNA synthetases of Eschenchia coli are subject to high rates of irreversible inactivation during growth under amino acid restriction, particularly when such growth is intermittent. This fact explains why derepression of these enzymes during amino acid restricted growth has been difficult to observe. Measurement of the true de novo rate of formation of a number of synthetases reveals that each is regulated by a mechanism that normally maintains synthesis at less than 25 to 30% of its maximum rate, and that is capable of regulating this rate over a 10- to 50-fold range. The regulation bears a superficial resemblance to repression of biosynthetic enzymes since in both cases manipulation of the amino acid supply affects the rate of enzyme formation; nevertheless, there are conditions under which the regulation of synthetase formation is opposite to that of the biosynthetic enzymes.