Evidence for complexation of P-450 IIC6 by an orphenadrine metabolite
| Autor: | Gordon F. Reidy, Michael Murray |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
medicine.medical_specialty
Metabolite medicine.medical_treatment Biophysics Reductase Biochemistry Steroid Hydroxylation chemistry.chemical_compound Cytochrome P-450 Enzyme System Orphenadrine Internal medicine medicine Animals Cytochrome P-450 Enzyme Inhibitors Ferricyanides Molecular Biology Progesterone biology Androstenedione Cytochrome P450 Cell Biology Rats Kinetics Endocrinology chemistry Phenobarbital Cytochrome P-450 CYP2B1 Steroid Hydroxylases Microsomes Liver Microsome biology.protein Oxidoreductases medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 166:772-779 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/0006-291x(90)90876-o |
| Popis: | Removal of the orphenadrine metabolite from its complex with rat liver P-450 IIB1 is associated with a discrepancy in the reactivation of IIB1 activity. Two possible explanations are that either (1) NADPH-P-450-reductase is inaccessible to the restored IIB1, or (2) complexation of other P-450s may occur. Exogenous P-450 reductase increased all pathways of steroid hydroxylation (1.9 to 3.6-fold) but did not enhance reactivation of IIB1-dependent steroid 16 beta-hydroxylation. Instead, P-450 IIC6-dependent progesterone 21-hydroxylase activity was increased after dissociation to 122% of control. IIC6 activity was also inhibited in vitro in microsomes from phenobarbital-induced rats (ki = 151 microM). Thus, orphenadrine appears to complex P-450 IIC6 as well as IIB1 in rat liver. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|