Competing models of mitochondrial energy metabolism in the heart are highly disputed. In addition, the mechanisms of reactive oxygen species (ROS) production and scavenging are not well understood. To deepen our understanding of these processes, a computer model was developed to integrate the biophysical processes of oxidative phosphorylation and ROS generation. The model was calibrated with experimental data obtained from isolated rat heart mitochondria subjected to physiological conditions and workloads.
Metabolism and Transport
Models of biochemical systems—including signaling pathways, electrophysiological systems, and cellular metabolism—are built from models of individual components such as enzymes, transporters, and ion channels. This databank of open source of component models uses a consistent notation, obeying a common set of criteria, with clear documentation and links to the primary literature. Code modules for enzymes and transporters can be downloaded in CellML or MATLAB, for use with the BISEN package.
Cardiac mitochondria play a crucial role in buffering and shaping cytosolic Ca2+ oscillations. They also meet the beat-to-beat energy demand of the heart by Ca2+-dependent stimulation of mitochondrial dehydrogenases (e.g, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase etc.). To date, a number of Ca2+ uptake pathways have been identified with the Ca2+ uniporter (CU) positioned as the major player.
Thermodynamic-based constraints on biochemical fluxes and concentrations are applied in concert with mass balance of fluxes in glycogenesis and glycogenolysis in a model of hepatic cell metabolism. Constraint-based modeling methods that facilitate predictions of reactant concentrations, reaction potentials, and enzyme activities are introduced to identify putative regulatory and control sites in biological networks by computing the minimal control scheme necessary to switch between metabolic modes.