Skip to Main content Skip to Navigation
Journal articles

Compartmentalized energy transfer in cardiomyocytes: use of mathematical modeling for analysis of in vivo regulation of respiration.

Abstract : The mathematical model of the compartmentalized energy transfer system in cardiac myocytes presented includes mitochondrial synthesis of ATP by ATP synthase, phosphocreatine production in the coupled mitochondrial creatine kinase reaction, the myofibrillar and cytoplasmic creatine kinase reactions, ATP utilization by actomyosin ATPase during the contraction cycle, and diffusional exchange of metabolites between different compartments. The model was used to calculate the changes in metabolite profiles during the cardiac cycle, metabolite and energy fluxes in different cellular compartments at high workload (corresponding to the rate of oxygen consumption of 46 mu atoms of O.(g wet mass)-1.min-1) under varying conditions of restricted ADP diffusion across mitochondrial outer membrane and creatine kinase isoenzyme "switchoff." In the complete system, restricted diffusion of ADP across the outer mitochondrial membrane stabilizes phosphocreatine production in cardiac mitochondria and increases the role of the phosphocreatine shuttle in energy transport and respiration regulation. Selective inhibition of myoplasmic or mitochondrial creatine kinase (modeling the experiments with transgenic animals) results in "takeover" of their function by another, active creatine kinase isoenzyme. This mathematical modeling also shows that assumption of the creatine kinase equilibrium in the cell may only be a very rough approximation to the reality at increased workload. The mathematical model developed can be used as a basis for further quantitative analyses of energy fluxes in the cell and their regulation, particularly by adding modules for adenylate kinase, the glycolytic system, and other reactions of energy metabolism of the cell.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00391359
Contributor : Sarah Hamant <>
Submitted on : Wednesday, June 3, 2009 - 5:43:33 PM
Last modification on : Wednesday, November 7, 2018 - 4:07:41 PM

Links full text

Identifiers

Collections

Citation

Mayis Aliev, Valdur Saks. Compartmentalized energy transfer in cardiomyocytes: use of mathematical modeling for analysis of in vivo regulation of respiration.. Biophysical Journal, Biophysical Society, 1997, 73 (1), pp.428-45. ⟨10.1016/S0006-3495(97)78082-2⟩. ⟨inserm-00391359⟩

Share

Metrics

Record views

132