The human hepatic organic cation transporter 1 (hOCT1) is a well-known transporter of both xenobiotic and endogenous cations. The substrates and inhibitors of hOCT1 are… Read More »Ligand-dependent modulation of hOCT1 transport reveals discrete ligand binding sites within the substrate translocation channel
The metabolism of testosterone to 6β-hydroxytestosterone (6β-OH-T) is a commonly used assay to evaluate human CYP3A enzyme activities. However, previous reports have indicated that CYP3A7… Read More »Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7
In recent years, a growing appreciation has developed for the importance of protein-protein interactions to modulate the function of drug metabolizing enzymes. Accompanied with this… Read More »Advances in the Understanding of Protein-Protein Interactions in Drug Metabolizing Enzymes through the Use of Biophysical Techniques
Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in… Read More »The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction
The cytochrome P450 (CYP) enzymes are a versatile superfamily of heme-containing monooxygenases, perhaps best known for their role in the oxidation of xenobiotic compounds. However,… Read More »Cytochrome P450 Enzyme Metabolites in Lead Discovery and Development
Defining the conformational states of cytochrome P450 active sites is critical for the design of agents that minimize drug-drug interactions, the development of isoform-specific P450… Read More »Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography
Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein-protein interactions play a… Read More »Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity
The human organic cation transporter 1 (OCT1) is a polyspecific transporter involved in the uptake of positively charged and neutral small molecules in the liver.… Read More »Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake
Human heme oxygenases 1 and 2 (HO-1 and HO-2) degrade heme in the presence of oxygen and NADPH-cytochrome P450 reductase, producing ferrous iron, CO, and… Read More »Role of cysteine residues in heme binding to human heme oxygenase-2 elucidated by two-dimensional NMR spectroscopy
The mechanisms of acetaminophen (APAP)-mediated hepatic oncotic necrosis have been extensively characterized. However, it was recently demonstrated that fed CD-1 mice have a transient caspase… Read More »Mouse strain-dependent caspase activation during acetaminophen hepatotoxicity does not result in apoptosis or modulation of inflammation