Flavin-containing monooxygenase activity in human liver microsomes

M. E. McManus, I. Stupans, W. Burgess, J. A. Koenig, P. M. Hall, D. J. Birkett

    Research output: Contribution to journalArticlepeer-review

    51 Citations (Scopus)

    Abstract

    Human liver microsomal flavin-containing monooxygenase activity has been studied using dimethylaniline N-oxidation and thiobenzamide S-oxidation. Except for one subject, the capacity of human liver microsomes to mediate these reactions were markedly increased at pH 8.4 compared to pH 7.4. The mean dimethylaniline N-oxidase activities at pH 7.4 and 8.4 in the four subjects tested were 2.49 ± 1.13 and 6.59 ± 4.04 nmol mg-1 min-1, respectively (mean ± SD, N = 4). The mean thiobenzamide S-oxidase activities at pH 7.4 and 8.4 were 1.39 ± 0.51 and 2.74 ± 1.28 nmol mg-1 min-1, respectively. At pH 7.4, an antibody to the human liver NADPH-cytochrome P-450 reductase inhibited dimethylaniline N-oxidation between 4 and 38%. The same antibody had no effect on this reaction at pH 8.4. Except for one subject, a battery of cytochrome P-450 inhibitors also had little effect on this reaction. Further, preincubating human microsomes at 45°C in the absence of NADPH for 4 min destroyed approximately 90% of the dimethylaniline N-oxidase activity. These data collectively suggested that the flavin-containing mono-oxygenase is the major enzyme mediating this reaction in human liver microsomes. In contrast to dimethylaniline N-oxidation, thiobenzamide S-oxidation was significantly inhibited by the anti-reductase at both pH 7.4 and 8.4, respectively. These data indicate that cytochromes P-450 contribute significantly to this reaction in human liver microsomes.

    Original languageEnglish
    Pages (from-to)256-261
    Number of pages6
    JournalDrug Metabolism and Disposition
    Volume15
    Issue number2
    Publication statusPublished - 1987

    Fingerprint Dive into the research topics of 'Flavin-containing monooxygenase activity in human liver microsomes'. Together they form a unique fingerprint.

    Cite this