|
| << vorige | volgende >> |
Tijdschrift beschrijving
Alle jaargangen van het bijbehorende tijdschrift
Alle afleveringen van het bijbehorende jaargang
Alle artikelen van de bijbehorende aflevering
Details van artikel 16 van 29 gevonden artikelen
| Titel: |
In Vitro Metabolism of the Fungicide and Environmental Contaminant trans-bromuconazole and Implications for Risk Assessment |
| Auteur: |
Mazur, Christopher S. Kenneke, John F. Tebes-Stevens, Caroline Okino, Miles S. Lipscomb, John C. |
| Verschenen in: |
Journal of toxicology and environmental health. Part A |
| Paginering: | Jaargang 70 (2007) nr. 14 pagina's 1241-1250 |
| Jaar: |
2007-01 |
| Inhoud: |
trans-Bromuconazole is a chiral chemical representative of a class of triazole derivatives known to inhibit specific fungal cytochrome P-450 (CYP) reactions. Kinetic measurements and delineation of metabolic pathways for triazole chemicals within in vitro hepatic microsomes are needed for accurate risk assessment and predictive in vivo physiological modeling. The studies described here were conducted with rat liver microsomes to determine Michaelis-Menten saturation kinetic parameters (Vmax and KM) for trans-bromuconazole using both substrate depletion and product formation reaction velocities. Kinetic parameters determined for trans-bromuconazole depletion at varying protein levels incubated at physiological temperature 37°C resulted in a KM value of 1.69 μM and a Vmax value of 1398 pmol/min/mg protein. The concomitant linear formation of two metabolites identified using liquid chromatography/time-of-flight mass spectrometry (LC/MS-TOF) and LC-MS/MS indicated hydroxylation of the trans-bromuconazole dichlorophenyl ring moiety. KM values determined for the hydroxylated metabolites were 0.87 and 1.03 μM, with Vmax values of 449 and 694 pmol/min/mg protein, respectively. Chemical inhibition assays and studies conducted with individual purified human recombinant enzymes indicated the CYP3A subfamily was primarily responsible for biotransformation of the parent substrate. Additionally, trans-bromuconazole was found to undergo stereoselective metabolism as evidenced by a change in the enantiomeric ratio (trans-/trans +) with respect to time. |
| Uitgever: |
Taylor & Francis |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
Details van artikel 16 van 29 gevonden artikelen
| << vorige | volgende >> |