Phenytoin 4-hydroxylation by rabbit liver P450IIC3 and identification of orthologs in human liver microsomes
| Autor: | C. J. Doecke, Lloyd Sansom, Michael E. McManus |
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| Rok vydání: | 1990 |
| Předmět: |
Phenytoin
medicine.medical_specialty medicine.medical_treatment Biophysics Hydroxylation Biochemistry Isozyme Substrate Specificity chemistry.chemical_compound Cytochrome P-450 Enzyme System Species Specificity Internal medicine otorhinolaryngologic diseases medicine Animals Humans heterocyclic compounds Molecular Biology biology digestive oral and skin physiology Cytochrome P450 Cell Biology biology.organism_classification nervous system diseases Isoenzymes stomatognathic diseases Endocrinology Anticonvulsant chemistry Microsoma Immunologic Techniques Microsomes Liver Microsome biology.protein Phenobarbital Rabbits medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 166:860-866 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/0006-291x(90)90889-u |
| Popis: | The ability of rabbit liver microsomes to 4-hydroxylate phenytoin to 5-(4-hydroxyphenyl)-5-phenylhydantoin was studied. No significant difference was observed between the capacity of control and rifampicin, phenobarbital, acetone, 2,3,7,8-tetrachlorodibenzo-p-dioxin and phenytoin induced rabbit liver microsomes to 4-hydroxylate phenytoin. In reconstitution experiments using six purified rabbit cytochromes P450 isozymes, only P450IIC3 was capable of 4-hydroxylating phenytoin whereas P450IA1, P450IA2, P450IIB4, P450IIIA6, and P450IVB1 were inactive. Further, anti-P450IIC3 IgG completely inhibited phenytoin 4-hydroxylase activity in rabbit liver microsomes. The above data suggest a major role for the constitutive isozyme P450IIC3 in phenytoin 4-hydroxylase activity in rabbit liver. In human liver microsomes P450IIC3 IgG inhibited phenytoin 4-hydroxylase activity by 66%, suggesting that an ortholog to rabbit P450IIC3 is in part responsible for this activity in man. |
| Databáze: | OpenAIRE |
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