A Metabolic Entropy Approach for Measurements of Systemic Metabolic Disruptions in Patho-Physiological States

Multicellular organisms maintain the stability of their internal environment using metabolic and physiological regulatory mechanisms that are disrupted during disease. The loss of homeostatic control results in a complex set of disordered states that may lead to metabolic network failure and irreversible system damage. We have applied a new statistical entropy-based approach to quantify temporal systemic disorder (divergence of metabolic responses) in experimental patho-physiological states, via NMR-spectroscopy generated metabolic profiles of urine. A recovery (R-) potential metric has also been developed to evaluate the relative extent to which defined metabolic processes are perturbed in the context of a global system in terms of multiple changes in concentrations of biofluid components accompanying the disrupted functional activity. This approach is sensitive to physiological as well as pathological interventions. We show that global disruptions of metabolic processes, lesion reversibility, and disorder in metabolic responses to a stressor can be visualized via metabolic entropy metrics, giving insights into biological robustness and thus providing a new tool for assessing deviation from homeostatic regulation.