Compartment Modeling for Mammalian Protein Turnover Studies by Stable Isotope Metabolic Labeling

Protein turnover studies on a proteome scale based on metabolic isotopic labeling can provide a systematic understanding of mechanisms for regulation of protein abundances and their transient behaviors. At this time, these large-scale studies typically utilize a simple kinetic model to extract protein dynamic information. Although many high-quality, protein isotope incorporation data are available from those experiments, accurate and additionally useful protein dynamic information cannot be extracted from the experimental data by use of the simple kinetic models. In this paper, we describe a formal connection between data obtained from elemental isotope labeling experiments and the well-known compartment modeling, and we demonstrate that an appropriate application of a compartment model to turnover of proteins from mammalian tissues can indeed lead to a better fitting of the experimental data.