Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats

The goal of these studies was to investigate the mechanisms by which amino acid supply regulates global rates of protein synthesis as well as the tran slation of ribosomal protein (rp) mRNAs in liver. In the experiments conduc ted, male weanling rats were trained over a 2-wk period to consume their da ily food intake within 3 h. On day 14, rats were fed the control diet or an isocaloric, isonitrogenous diet lacking glycine, tryptophan, leucine, or t he branched-chain amino acids (BCAA) for 1 h. Feeding Trp-, Leu-, or BCAA-d eficient diets resulted in significant reductions in serum insulin, hepatic protein synthesis, eukaryotic initiation factor 213 (eIF2B) activity, and phosphorylation of eIF4E-binding protein 1 (4E-BP1) and ribosomal protein S 6 kinase (S6K1). Phosphorylation of eIF2 alpha was inversely related to eIF 2B activity under all conditions. Alterations in the hepatic synthesis of r p were assessed by changes in the distribution of rp (S4, S8, L26) mRNAs ac ross sucrose density gradients and compared with non-rp (beta -actin, album in) mRNAs. In all dietary treatments, non-rp mRNAs were mostly polysome ass ociated. Conversely, the proportion of rp mRNAs residing in polysomes was t wo- to fivefold less in rats fed diets lacking tryptophan, leucine, or BCAA compared with rats fed the control diet. Total hepatic abundance of all mR NAs examined did not differ among treatment groups. For all parameters exam ined, there were no differences between rats fed the glycine-deficient diet and rats fed the control diet. The data suggest that essential amino acid (EAA) deficiency inhibits global rates of liver protein synthesis via a blo ck in translation initiation. Additionally, the translation of rp mRNAs is preferentially repressed in association with decreased S6K1 phosphorylation .