It contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways: Phase I (functionalization reactions). The enzymes involved in Phase I reactions are
Genetic variation in CYP3A4 can significantly impact the enzyme’s expression, activity, and, consequently, the metabolism of drugs that are substrates of this enzyme. CYP3A4 is encoded by the CYP3A4 gene (located on chromosome 7), and like many other drug-metabolizing enzymes, it exhibits ...
other tissue components. Reducing the concentration of free solute causes a decrease in the rate of passage across membrane barriers and may alter drug distribution at equilibrium, as reflected in Vddeterminations. Drug sequestration can also affect the processes of absorption, metabolism, and ...
The main regulator of cellular stress is PKM2, a key enzyme in glycolysis [63] that promotes reductive glutamine metabolism [61]. PKM2 knockout in healthy HSCs has shown no substantial defect minus loss of reconstitution potential observed upon multiple serial transplants. Additionally, PKM2 knockou...
2.3Alterations in metabolism of drug-resistant cancer cells Based on its enhanced proliferation rate, cancer is a disease characterized by the constant generation of new biomass. Consequently, to satisfy their high demand for new building blocks, it is not surprising that malignant cells differ in ...
Finally, it is possible that certain compounds are active in only one cell line due to metabolism or other cell-specific properties, and further testing is required to determine their suitability for downstream drug development.Based on our prioritization, we tested activity of representative hits ...
内容提示: Current Drug Metabolism, 2001, 2, 117-137 117 1389-2002/01 $28.00+.00 © 2001 Bentham Science Publishers Ltd.Analysis of Mammalian Cytochrome P450 Structure and Function by Site-Directed MutagenesisT. L. Domanski and J.R. Halpert*Department of Pharmacology and Toxicology, University...
Flavonoids can alter the pharmacokinetics of drugs by modifying the activity of drug-metabolising enzymes and drug transporters being important for drug absorption, distribution, metabolism, and excretion (Margină et al., 2015, Rodríguez-Fragoso et al., 2011). Whereas inhibition of these proteins...
In vitro human recombinant cytochrome P450 (CYP) studies indicated that ziritaxestat was primarily metabolized by CYP3A4 with minor contributions (maximum of 2.1%) to metabolism from other phase 1 enzymes. Increases in messenger RNA expression when 0.1 to 30 μM of ziritaxestat was incubated ...
Phase I reactions are usually rate-limiting in drug metabolism. Prior exposure to the compound, or other compounds, can induce the expression of Phase I enzymes however, and thereby increase substrate flux through the metabolic pathways. (See Klaassen, C. D., Amdur, M. O. and J. Doull (...