A simulation study on the constancy of cardiac energy metabolites during workload transition

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp7468-list-0001">The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant during physiological cardiac workload transition.How this is accomplished is not yet clarified, though Ca²⁺ has been suggested to be one of the possible mechanisms.We constructed a detailed mathematical model of cardiac mitochondria based on experimental data and studied whether known Ca²⁺‐dependent regulation mechanisms play roles in the metabolite constancy.Model simulations revealed that the Ca²⁺‐dependent regulation mechanisms have important roles under the in vitro condition of isolated mitochondria where malate and glutamate were mitochondrial substrates, while they have only a minor role and the composition of substrates has marked influence on the metabolite constancy during workload transition under the simulated in vivo condition where many substrates exist.These results help us understand the regulation mechanisms of cardiac energy metabolism during physiological cardiac workload transition.