Systems Biology Approaches to Enzyme Kinetics.
Methods Mol Biol
; 2342: 419-440, 2021.
Article
em En
| MEDLINE
| ID: mdl-34272703
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. Two examples are provided. First, a model of hydrogen peroxide clearance during chemotherapy treatment serves as a basis to discuss an example of sensitivity analysis. Second, an example of doxorubicin bioactivation is used for discussing points of consideration when constructing and analyzing network models of drug metabolism.
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Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Biologia de Sistemas
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Enzimas
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Peróxido de Hidrogênio
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article