Regulation of the First Step of the Initiation of Brain Protein Synthesis by Guanosine Diphosphate

Abstract: Initiation factor elF-2-like activity has been measured in the 0.5 M-KCl wash of rat brain microsomes. Ternary complex formation (elF-2 GTP Met-tRNA_r), one of the early steps in protein synthesis initiation, is optimal in a high-[K⁺], low-[Na⁺] environment. Mg²⁺, Ca²⁺, Li⁺, spermine and spermidine reduce and the antibiotic aurin tricarboxylic acid can effectively eliminate ternary complex formation. The formation of ternary complex requires GTP or its nonhydrolyzable analog, GMP-P(NH)P. Ternary complex formation is particularly sensitive to the ratio of GDP to GTP. When the ratio of GDP to GTP added is 1: 10, ternary complex formation is inhibited between 40 and 50% over a 30-fold concentration range of GTP. Other nucleotides exert little inhibition. These results suggest that the regulation of brain protein synthesis initiation may be tightly linked to the ratios of guanosine nucleotide concentrations in brain tissue.