Analysis of dynamic labeling data

Abstract

Comprehensive assessments of the organization and regulation of metabolic pathways cannot be limited to steady-state measurements alone but require dynamic time series data. One experimental means of generating such data consists of radioactively labeling precursors and measuring their fate over time. While labeling experiments belong to the standard repertoire of biological laboratory techniques, corresponding mathematical tools for analyzing the non-linear dynamics of tracers are scarce. The article addresses this issue, using Biochemical Systems Theory as the modeling framework. The description of the dynamics of labeled metabolites alone is difficult, but it is demonstrated that these difficulties are easily overcome by setting up dynamic models in two or three blocks, one for the kinetics of the total pools, the second just for the labeled portions, and the third, optional, block for the remaining unlabeled components. Since the dynamic model is not limited in complexity and can account for linear pathways, converging and diverging branches, cycles, and the various observed modes of regulation, the proposed method of non-linear tracer analysis is rather general and permits simulations of most standard labeling experiments, both at steady state and during transients.