Abstract 384: Leucine, Serine and Methionine Differentially Affect Protein Synthesis in Rat Heart

Abstract

Alternating flux through metabolic pathways enables the heart to rapidly adapt to stress. As a consequence, compensatory mechanisms are often associated with changes in mitochondrial function and cellular redox state. The collective importance of these metabolic changes to energy provision and protein turnover remains unknown. We therefore integrated radioactive tracer studies with a mathematical model of cardiac metabolism - CardioNet. We assessed through flux rate analysis the impact of altered amino acid supply on mitochondrial metabolism. In combination with leucine, both serine and methionine resulted in a two- to threefold increased variance of mitochondrial flux rates. Next we used the isolated working rat heart to determine whether supply of glucose and leucine, in combination with either serine or methionine at different concentrations, affects cardiac protein turnover and energy provision. While glucose remained the major energy source, oxidation of leucine contributed to ATP production. Methionine, but not serine, markedly increased both myocardial oxygen consumption and cardiac power at normal physiologic concentrations. Protein synthesis rates (units given in μmol/min/g dry wt) did not significantly differ from leucine alone (0.037±0.001) or leucine in combination with serine (0.038±0.003) or methione (0.045±0.007). However, with increased serine supply, protein synthesis significantly increased (0.0907±0.009) compared to methionine (0.059±0.006, p=0.024) or leucine only (0.015±0.002, p=0.031). The results suggest that myocardial protein synthesis is differentially regulated by specific amino acids.