title: Systems biology approaches to enzyme kinetics: analyzing network models of drug metabolism.
abstract: Intracellular drug metabolism involves transport, bioactivation, conjugation, and other biochemical steps. The dynamics of these steps are each dependent on a number of other cellular factors that can ultimately lead to unexpected behavior. In this review, we discuss the confounding processes and coupled reactions within bioactivation networks that require a systems-level perspective in order to fully understand the time-varying behavior. When converting known in vitro characteristics of drug-enzyme interactions into descriptions of cellular systems, features such as substrate availability, cell-to-cell variability, and intracellular redox state deserve special focus. An example of doxorubicin bioactivation is used for discussing points of consideration when constructing and analyzing network models of drug metabolism.
authors: Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, USA.
authors: Nnenna A
authors: NA
authors: Finn
authors: Melissa L
authors: ML
authors: Kemp
mesh_terms: D004317:Doxorubicin / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007700:Kinetics; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods*
chemical_list: D004798:Enzymes; D004364:Pharmaceutical Preparations; D004317:Doxorubicin