10 - Tracer Experiment Design for Metabolic Fluxes Estimation in Steady and Nonsteady State

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Abstract

The purpose of this chapter is to illustrate how tracer experiments can be designed to quantify metabolic fluxes. We will review the principles of tracer experimental design by describing the metabolic system under study by a compartmental model with a single pool accessible for measurement (usually plasma) that exchanges with a network of inaccessible pools. We will introduce the notion of tracee (i.e., the endogenous substance under study) versus tracer (i.e., a radioactive or a stable isotope that is administered exogenously and has, at least ideally, the same metabolic fate as the tracee). We will explain how tracer administration allows one to generate dynamic data that help in quantifying the metabolic fluxes of the tracee. Finally, we will illustrate the main approaches to the design of the format of tracer administration under steady- and nonsteady-state conditions.

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    2018, Biophysical Journal
    Citation Excerpt :

    This approach of linking two systems has been applied to the analysis of non-steady-state tracer experiments at levels of biological organization from single cells (7,57) to human metabolic physiology (68) and pharmaceutical development (69). The above “linking” approach differs from classic methods of estimating fluxes in non-steady states, which employ additional tracers of the same molecule to supply the required information (70) or employ hybrid algebraic and stochastic methods (71). These classic methods consider only tracer dynamics and do not directly account for the impact of the underlying nonlinear dynamics in non-steady state experiments.

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