Integrated and Organized Cellular Energetic Systems: Theories of Cell Energetics, Compartmentation, and Metabolic Channeling

Bioenergetics as a part of biophysical chemistry and biophysics is a quantitative science that is based on several fundamental theories. The definition of energy itself is given by the first law of thermodynamics, and application of the second law of thermodynamics shows that living cells can function as open systems only where the internal order (low entropy state) is maintained due to increasing the entropy in the surrounding medium (Schrödinger's principle of negentropy). For this, the exchange of mass is needed, which gives rise to metabolism as the sum of catabolism and anabolism, and the free energy changes during catabolic reactions supply energy for all cellular work - osmotic, mechanical, and biochemical. The free energy changes during metabolic reactions obey the rules of chemical thermodynamics, which deals with Gibbs free energy of chemical reactions and with electrochemical potentials. For application of these theories to the integrated systems in vivo, complex cellular organization should be accounted for: macromolecular crowding; metabolic channeling and functional coupling mechanisms due to close and tight protein-protein interactions; compartmentation of the enzymes due to their attachment to the subcellular membranes or connection to the cytoskeleton; and both macro- and microcompartmentation of substrates and metabolites in the cells. Because of this, almost all processes important for cell life are localized within small areas of the cell, and for their integration effective systems of communication, including compartmentalized energy transfer systems, are required. These are represented in muscle cells by the phosphotransfer networks, mostly by the creatine kinase and adenylate kinase systems, whose alterations under ischemic conditions contribute significantly to acute ischemic contractile failure of the heart.