and, 3) the glutamine synthetase deadenylylating enzyme. Equation 4 shows the adenylylated and unadenylylated forms of glutamine synthetase, with their respective properties, as well as the enzymes which interconvert the two forms, and their effectors.of the products of glutamine metabolism. In this form glutamine synthetase activity is thus further diminished by the accumulated nitrogenous metabolites, which has as its result the lowering of the level of glutamine in the cell. It is clear from this scheme that conditions of nitrogen starvation, with a correspondingly low nitrogen saturation ratio, lead to activation of the deadenylylating enzyme as well as to an inhibition of the adenylyltransferase, owing to the alterations in the relative levels of glutamine and a-ketoglutarate. This results in the formation of relatively unadenylylated glutamine synthetase, the form of the enzyme which is intrinsically more active and less sensitive to feedback inhibition. In this condition, ammonia will be converted into nitrogenous metabolites with high efficiency.On the other hand, with high levels of the nitrogen saturation ratio, as might be expected with a surfeit of nitrogen-containing compounds,thedeadenylylating enzyme would be inhibited and the adenylyltransferase activated. The result of this reciprocal enzyme control would be to convert the glutamine synthetase to the adenylylated form, which is less active and additionally more susceptible to inhibition by several Less active form More sensitive to feedback inhibition MnZ+ specificThe three-enzyme nitrogen regulatory system has as its most obvious role the preservation of homeostasis in cellular nitrogen metabolism; any shift away from the "normal" nitrogen saturation ratio is accompanied by adjustments in the three enzymes which tend to restore the ratio toward the preexisting level. These intricate controls have as an ancillary effect the preservation of cellular ATP, since both glutamine synthesis and adenylylation of glutamine synthetase consume ATP; in fact, the adenylylation-deadenylylation system without reciprocal controJ would be a wasteful ATPase activity. The reason for the nucleotide controls in the adenylylation and deadenylylation phenomena is as yet obscure; a possible link between glutamine synthesis and polynucleotide metabolism is suggested by the effects of ribonucleic acid species on the deadenylylating system.
