A role for leucine in regulation of protein turnover in working rat hearts

Effect of leucine on protein turnover was examined in perfused hearts provided with 1 (0.2 mM) or 5 times (1 mM) plasma levels of leucine and normal plasma levels of other amino acids. When hearts were perfused as Langendorff or working preparations with buffer that contained 15 mM glucose, protein degradation was 2-3 times faster than protein synthesis. As a result, the heart was in marked negative nitrogen balance. Addition of 1 mM leucine significantly improved the nitrogen balance (24-33%) by stimulating protein synthesis in Langendorff preparations (25%) and inhibiting protein degradation in both preparations (14-29%). The stimulatory effect of leucine on protein synthesis was associated with a reduction in levels of ribosomal subunits. In hearts supplied physiological levels of glucose, lactate, beta-hydroxybutyrate, insulin, and glucagon, protein synthesis was more nearly equal to protein degradation. Provision of 1 mM leucine stimulated protein synthesis only in Langendorff preparations (32%) but did not have a significant effect on protein degradation in either preparation. Although leucine did not have a significant effect on either protein synthesis or degradation in working hearts, nitrogen balance became positive with addition of 1 mM leucine. These results suggest that leucine may exert an effect on myocardial nitrogen balance in vivo under conditions that elevate plasma leucine concentrations.