LEUCINE AFFECTS THE METABOLISM OF VALINE BY ISOLATED-PERFUSED RAT HEARTS - RELATION TO BRANCHED-CHAIN AMINO-ACID ANTAGONISM

This study was conducted to determine the effects of different concent rations of leucine on the transport, transamination and oxidation of v aline and on incorporation of valine into heart proteins in the isolat ed perfused rat heart. Valine metabolism was studied in rat hearts per fused with medium containing glucose and graded levels of L-leucine. I n transport studies L-phenylalanine was also tested. Uptake of L-[1-C- 14]valine (0.2 mmol/L) was significantly reduced (similar to 50%) by i nclusion of 0.2 mmol/L phenylalanine or leucine, and by -70% by inclus ion of 1.0 mmol/L phenylalanine or leucine in the perfusate. Transamin ation of valine decreased by 37 and 48%, and oxidation of valine by 53 and 71%, respectively, when 0.2 or 1.0 mmol/L leucine was included in the perfusate. Tissue concentrations of valine decreased by 43, 48 an d 62% in the presence of 0.2, 0.5 and 1.0 mmol/L leucine, respectively ; tissue concentrations of leucine, glutamate and alanine increased si milar to 11-fold, 1.2-fold and 0.5-fold, respectively, when 1.0 mmol/L leucine was present in the perfusate. Addition of 0.2-1.0 mmol/L leuc ine did not affect incorporation of valine into heart proteins. We con clude that 1) competition among large neutral amino acids for transpor t into heart occurs at physiological concentrations of these amino aci ds in plasma; 2) inhibition of valine uptake by leucine can limit the rate of valine catabolism in heart; and 3) depletion of tissue valine concentration by an excess of leucine did not affect the rate of prote in synthesis.