The heart oxidizes fatty acids, carbohydrates and ketone bodies inside the citric acid cycle (CAC) to generate the reducing equivalents needed for ATP production. Competition between these substrates makes it difficult to estimate the extent of pyruvate oxidation. Previously, hyperpolarized pyruvate detected propionate mediated activation of carbohydrate oxidation, even in the presence of acetate. In this report, the optimal concentration of propionate for activation of glucose oxidation is measured in mouse hearts perfused in Langendorff mode. This study was performed with a more physiologically relevant perfusate than the previous work. Increasing concentrations of propionate did not cause adverse effects on myocardial metabolism, as evidenced by unchanged O2 consumption,citric acid cycle (CAC) flux, and developed pressures. One mM propionate was sufficient to achieve significant increases in PDH flux (3x) and anaplerosis (6x) as measured by isotopomer analysis. These results further demonstrate the potential of propionate as an aid for the correct estimation of total carbohydrate oxidative capacity in the heart. However, LC/MS based metabolomics detected large changes (~ 30 fold) in malate and fumarate pool sizes. This observation leads to a key observation regarding mass balance in the CAC: flux through a portion of the cycle can be drastically elevated without changing the O2 consumption.
- substrate selection
- fatty acids
- isotopomer analysis
- Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology