Mechanisms and modeling of energy transfer between intracellular compartments

Abstract

Mitochondria are the primary sources of ATP production, but the sites and processes that consume ATP are often located at considerable distances from the source of regeneration of ATP from ADP and Pi. The transfer of energy occurs in the highly organized and compartmentalized intracellular medium. The coupling of energy-producing and energy-consuming processes is important and involves metabolic channeling and functional coupling mechanisms between different enzymes, multienzyme systems, and transporters. In muscle, coupling of creatine kinase (CK) and adenylate kinase (AK) reactions is essential for minimizing energy gradients, reducing energy dissipation, and directing energy to sites and pathways for specific processes. Such processes include transfer of ATP from mitochondria to cell membrane, to myofibrils, to nucleus, or to sarcoplasmic reticulum (SR). Energy transfer via the kinase systems or localized glycolytic enzymes to membranes in order to support transport processes (e.g., glutamate loading of synaptic vesicles or Na+/K+-ATPase activity) is critical for brain function, but little is known of these processes in brain cells. Therefore, this chapter provides a framework for approaching this issue in brain cells using the cardiac system as a model with description of main mechanisms involved and methods of their quantitative description. First, we analyze the experimental data showing compartmentation of the energy metabolism due to the high degree of structural organization of the cell. Then we describe the principles of mathematical modeling of biological systems, followed by mathematical and thermodynamic analysis of interaction between proteins. Finally, we use the mathematical model of the compartmentalized energy transfer to find a solution to the long-discussed problem of regulation of cardiac respiration under physiological conditions, where cardiac muscle energetics is regulated by the Frank-Starling law. Similarities and differences between compartmentalized energy transfer in cardiac and brain cells are analyzed briefly. © 2007 Springer Science+Business Media, LLC.