Transfer Ribonucleic Acids in the Developing Brain: The Effect of the Convulsant Methionine Sulfoximine on tRNA Function

Abstract

Effects of the convulsant L-methionine-dl-sulfoximine (MSO) on brain transfer ribonucleic acids (tRNAs) were discovered through a comparative biochemical analysis of tRNAs from control and MSO-treated (150 mg/kg, single dose) 3-day old rats. The study of the in vitro formation of aminoacyl-tRNA, the key intermediate in translation, coupled with benzoylated-DEAE cellulose (BCD) chromatography of control and MSO-tRNAs, revealed a relationship between the molecular structure of tRNA, as affected by MSO, and its function in amino acid acceptance. Post-charging of tRNA following BDC chromatography revealed 3 tRNAphe and 3 tRNAlys isoacceptors in control brains. The administration of MSO resulted in a significant alteration of the mobility of all 6 isoacceptors on BDC and in a marked reduction of their aminoacylating capacity when compared to control molecules. The MSO-elicited impairment of aminoacyl-tRNA formation was studied using both liver (heterologous) and brain (homologous) aminoacyl-tRNA synthetase preparations. Acceptance of lysine and phenylalanine by MSOtRNA was uniformly lower than acceptance by control tRNA and was reflected by a drop in the Vmax values for the two amino acids. Different optima for[K+] and [CTP] were also found when phenylalanine acceptance by control and MSO-tRNA was compared.