Further characterization of rat brain flavin-containing monooxygenase. Metabolism of imipramine to its N-oxide.
Biochem Pharmacol
; 51(11): 1469-75, 1996 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-8630088
ABSTRACT
Flavin-containing monooxygenase (FMO) activity was compared in rat liver and brain microsomes by estimating the actual amount of imipramine N-oxide relative to the corresponding activity, measured using substrate-stimulated rates of NADPH oxidation. The activities measured as NADPH oxidation rates were significantly higher than those estimated from the N-oxide formed. The brain FMO activity was detectable only in the presence of detergents (sodium cholate or Lubrol PX) or in microsomes that were freeze-thawed several times. The antibody to rabbit pulmonary FMO selectively inhibited imipramine N-oxidation. The antiserum to the rat liver NADPH cytochrome P-450 reductase had no effect on imipramine N-oxidation, indicating the noninvolvement of cytochrome P-450 in the above metabolic pathway. A flavin-containing monooxygenase was partially purified from the rat brain microsomes using sequential chromatography on n-octylamino-Sepharose 4B, DEAE-Sephacel and 2',5'-ADP agarose. The purified FMO was resolved by SDS-PAGE into two bands (approximately 57 and 61 KDa, respectively) both of which cross-reacted with antibody to rabbit pulmonary FMO. The purified enzyme metabolized imipramine and the model substrate methimazole to their respective N-oxide and S-oxides.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigenases
/
Encéfalo
/
Imipramina
/
Antidepressivos Tricíclicos
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Índia