Effects of noncarbohydrate substrates on protein synthesis in hearts from fed and fasted rats

An overnight fast reduced RNA content and resulted in lower rates and efficiency of protein synthesis when rat hearts were perfused in vitro and supplied glucose as oxidizable substrate. Decreased efficiency of synthesis was associated with development of a block in peptide chain initiation in hearts of both fed and fasted rats. Provision of pyruvate increased the rate and efficiency of protein synthesis in fasted but not fed tissue, and partially overcame the initiation block in both groups. A mixture of glucose, pyruvate and insulin increased the efficiency of protein synthesis and decreased ribosomal subunit content to similar values in both groups of hearts. Noncarbohydrate substrates, including pyruvate, lactate, acetoacetate and beta-hydroxybutyrate, supported higher rates of protein synthesis than glucose in hearts of fasted, but not fed rats. However, mixtures of glucose and either pyruvate, acetoacetate or beta-hydroxybutyrate increased the synthetic rate in fed tissue. Provision of noncarbohydrate substrates increased energy availability, as indicated by higher creatine-P/creatine ratios in both groups of hearts, but the synthetic rate increased as a function of creatine-P/creatine ratio only in the fasted tissue. Octanoate and leucine accelerated protein synthesis and increased energy availability in the fed tissue. The mixtures of glucose and noncarbohydrate substrates or octanoate elevated glucose-6-P content. These studies indicate that an overnight fast decreased the capacity for protein synthesis and modified the regulation of synthesis by noncarbohydrate substrates.