A Quantitative Study of Oxygen as a Metabolic Regulator
An acute reduction in oxygen delivery to a tissue is associated with metabolic changes aimed at maintaining ATP homeostasis. However, given the complexity of the human bioenergetic system, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). In particular, we are interested in determining mechanisms relating cellular oxygen concentration to observed metabolic responses at the cellular, tissue, organ, and whole body levels and in quantifying how changes in tissue oxygen availability affect the pathways of ATP synthesis and the metabolites that control these pathways.
In this study, we extend a previously developed mathematical model of human bioenergetics, to provide a physicochemical framework that permits quantitative understanding of oxygen as a metabolic regulator. Specifically, the enhancement—sensitivity analysis—permits studying the effects of variations in tissue oxygenation and parameters controlling cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The analysis can distinguish between parameters that must be determined accurately and those that require less precision, based on their effects on model predictions. This capability may prove to be important in optimizing experimental design, thus reducing use of animals.
Key wordsMetabolism metabolic control oxygen regulation sensitivity analysis
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- 1.Gutierrez G. Cellular energy metabolism during hypoxia. Crit Care Med 1991; 19:619626.Google Scholar
- 7.Radhakrishnan K. Combustion Kinetics and Sensitivity Analysis Computations. In: Oran ES, Boris JP, editors. Numerical Approaches to Combustion Modeling. Washington DC: AIAA, 1991; 83–128.Google Scholar
- 9.Radhakrishnan K. LSENS. A General Chemical Kinetics and Sensitivity Analysis Code for Homogeneous Gas-Phase Reactions. I. Theory and Numerical Solution Procedures. Washington DC, NASA Reference Publication 1328, 1994.Google Scholar
- 10.Radhakrishnan K. LSENS, The NASA Lewis Kinetics and Sensitivity Analysis Code, Reston, VA: American Institute of Aeronautics and Astronautics 99–2394, 1999.Google Scholar