Further characterization of rat brain flavin-containing monooxygenase: metabolism of imipramine to its N-oxide

Bhagwat, Shripad V. ; Bhamre, Shubhada ; Boyd, Michael R. ; Ravindranath, Vijayalakshmi (1996) Further characterization of rat brain flavin-containing monooxygenase: metabolism of imipramine to its N-oxide Biochemical Pharmacology, 51 (11). pp. 1469-1475. ISSN 0006-2952

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/000629...

Related URL: http://dx.doi.org/10.1016/0006-2952(96)00088-3

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.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Brain; Antidepressants; Flavin-containing Monooxygenase; Drug Metabolism; Monooxygenases; Psychoactive Drugs; FMO; Flavin-containing Monooxygenase
ID Code:40642
Deposited On:24 May 2011 13:42
Last Modified:24 May 2011 13:42

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