Key result
In a computational model of the working heart, disabling the creatine kinase system caused considerable oscillations in cytoplasmic ADP and ATP levels and deteriorated energetic stability, while eliminating myoglobin had almost no impact.
Computational modeling demonstrates that the creatine kinase system, but not myoglobin, plays an essential role in stabilizing the cytoplasmic ATP hydrolysis potential during beat-to-beat transients in the working heart.
Creatine kinase, not myoglobin, stabilizes modeled cardiac energetics; leaves open in vivo relevance and therapeutic targeting.
BACKGROUND: The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate. RESULTS: The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (DeltaGATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of DeltaGATPase in the beating heart. CONCLUSION: The CK system stabilizes DeltaGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.
No takes yet. Share an insight, caveat, or question.
Wu et al. (2009) studied Cardiac energetics. In silico elimination of myoglobin or creatine kinase system vs. Normal system with myoglobin and creatine kinase activity was evaluated on Cytoplasmic ATP hydrolysis potential (ΔGATPase) and metabolite oscillations. In a computational model of the working heart, disabling the creatine kinase system caused considerable oscillations in cytoplasmic ADP and ATP levels and deteriorated energetic stability, while eliminating myoglobin had almost no impact.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: