The characteristics of the microsomal hydroxylation of tolbutamide
| Autor: | Serge St-Hilaire, Pierre M. Bélanger |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Hemeproteins
medicine.medical_specialty Cytochrome Physiology Tolbutamide Metabolite Guinea Pigs In Vitro Techniques Hydroxylation Mixed Function Oxygenases Mice chemistry.chemical_compound Cytochrome P-450 Enzyme System Species Specificity Cricetinae Safrole Physiology (medical) Internal medicine medicine Animals Chromatography High Pressure Liquid Pharmacology biology Rats Inbred Strains General Medicine Monooxygenase Rats Isoenzymes Kinetics Endocrinology chemistry Biochemistry Isosafrole Enzyme Induction Phenobarbital Microsomes Liver biology.protein Microsome Rabbits medicine.drug |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 69:400-405 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y91-061 |
| Popis: | The in vitro metabolism of tolbutamide to the hydroxymethyl derivative was studied using hepatic microsomal homogenates. The hydroxymethyl metabolite was quantitated by HPLC. The hepatic microsomal hydroxylase was completely inhibited by carbon monoxide and was NADPH dependent. Metyrapone, α-naphthoflavone, phenelzine, mercuric chloride, and nitrogen significantly inhibited the reaction indicating the involvement of the cytochrome P-450 monooxygenase. Species variation showed that the order of hepatic microsomal activity was rat > rabbit >> guinea pig >> mouse and hamster. The reaction increased with time up to 40 min and followed Michaelis–Menten kinetics in rat liver microsomes with apparent Km and Vmax values of 224.4 μM and 359.9 pmol∙mg−1∙min−1, respectively. The reaction was induced by phenobarbital but was depressed after pretreatment with 3-methylcholanthrene and isosafrole. However, expression of the hydroxylase activity per nanomoles of cytochrome P-450 showed that the activity was much higher in liver microsomes of isosafrole pretreated rats. These results indicate the involvement of different isozymes of cytochrome P-450 in the microsomal hydroxylation of tolbutamide.Key words: tolbutamide metabolism, tolbutamide hydroxylation, microsomal hydroxylation, microsomal metabolism of tolbutamide, hepatic metabolism of tolbutamide. |
| Databáze: | OpenAIRE |
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