Marcaine, a selective inhibitor of eucaryotic aminoacylation

The effects of marcaine, a myotoxic drug, on the aminoacylation of transfer ribonucleic acid (rRNA) have been studied. The drug is a potent inhibitor of the acylation of rat liver tRNA with leucine and isoleucine but is only mildly inhibitory (or not inhibitory) to acylation with a number of other amino acids which were tested. Further, marcaine inhibited aminoacylation in cell-free systems using components from several mammalian tissues, including muscle, from yeast, and from wheat germ. No effect of the drug was observed in aminoacylation systems from several bacterial species which were tested. The drug inhibits acylation with leucine and isoleucine competitively but exhibited noncompetitive kinetics when the concentrations of adenosine 5'-triphosphate (ATP) and tRNA were varied. Marcaine was also a competitor of leucine in the ATP--pyrophosphate exchange reaction. Two structural analogues of marcaine, carbocaine and xylocaine, also inhibited acylation of rat liver tRNA with leucine but in a noncompetitive fashion. On a molar basis, marcaine appears to be the most effective inhibitor of the three drugs tested.