A mathematical model of the P-glycoprotein pump as a mediator of multidrug resistance
| Autor: | Doris L. Slate, Seth Michelson |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Pharmacology
biology Facilitated diffusion Chemistry General Mathematics General Neuroscience Immunology Diaphragm pump Membrane transport General Biochemistry Genetics and Molecular Biology Transmembrane protein Cell membrane medicine.anatomical_structure Computational Theory and Mathematics Biochemistry Cytoplasm biology.protein Biophysics medicine Efflux General Agricultural and Biological Sciences General Environmental Science P-glycoprotein |
| Zdroj: | Bulletin of Mathematical Biology. 54:1023-1038 |
| ISSN: | 0092-8240 |
| DOI: | 10.1016/s0092-8240(05)80093-x |
| Popis: | Cells displaying the classic multidrug resistant (MDR) phenotype possess a transmembrane protein (p170 or P-glycoprotein) which can actively extrude cytotoxic agents from the cytoplasm. A mathematical model of this drug efflux pump has been developed. Outward transport is modeled as a facilitated diffusion process. Since energy-dependent efflux of cytotoxic agents requires that ATP also bind to p170, the model includes a dynamic calculation for efflux rate which considers Michaelis-Menten kinetics for both the substrate agent and ATP. The final system consists of one partial differential equation (PDE) for the facilitated diffusion of substrate agents out of the cell, a 2 × 2 ordinary differential equation (ODE) system for the dynamic calculation of the ATP-ADP pool, and a dynamic algebraic calculation of the efflux rate given substrate levels at the interior cell membrane interface and ATP levels in the cell. A stability analysis of the ATP-ADP pool distribution and a simplistic closed form solution of the linearized PDE are included. Numerical simulations are also provided. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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