ROLES OF HUMAN CYP2A6 AND 2B6 AND RAT CYP2C11 AND 2B1 IN THE 10-HYDROXYLATION OF (â)-VERBENONE BY LIVER MICROSOMES
(â)-Verbenone, a monoterpene bicyclic ketone, is a component of the essential oil from rosemary species such as Rosmarinus officinalis L ., Verbena triphylla , and Eucalyptus globulus and is used for an herb tea, a spice, and a perfume. In this study, (â)-verbenone was found to be converted to 1...
Saved in:
Published in | Drug metabolism and disposition Vol. 31; no. 8; pp. 1049 - 1053 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.08.2003
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | (â)-Verbenone, a monoterpene bicyclic ketone, is a component of the
essential oil from rosemary species such as Rosmarinus officinalis
L ., Verbena triphylla , and Eucalyptus globulus and is
used for an herb tea, a spice, and a perfume. In this study, (â)-verbenone was
found to be converted to 10-hydroxyverbenone by rat and human liver microsomal
cytochrome P450 (P450) enzymes. The product formation was determined by
high-performance liquid chromatography with UV detection at 251 nm. There was
a good correlation between activities of coumarin 7-hydroxylation and
(â)-verbenone 10-hydroxylation catalyzed by liver microsomes of 16 human
samples, indicating that CYP2A6 is a principal enzyme in (â)-verbenone
10-hydroxylation in humans. Human recombinant CYP2A6 and CYP2B6 catalyzed
(-)verbenone 10-hydroxylation at V max values of 15 and 21
nmol/min/nmol P450 with apparent K m values of 16 and 91
μM, respectively. In contrast, rat CYP2A1 and 2A2 did not catalyze
(â)-verbenone 10-hydroxylation at all, suggesting that there were
species-related differences in the catalytic properties of human and rat CYP2A
enzymes in the metabolism of (â)-verbenone. In the rat, recombinant CYP2C11,
CYP2B1, and CYP3A2 catalyzed (â)-verbenone 10-hydroxylation with
V max and K m ratios (ml/min/nmol P450)
of 0.73, 0.20, and 0.03, respectively. Male-specific CYP2C11 was a major
enzyme in (â)-verbenone 10-hydroxylation by untreated rat livers, and CYP2B1
catalyzed this reaction in liver microsomes of phenobarbital-treated rats. Rat
CYP2C12, a female-specific enzyme, did not catalyze (-)verbenone
10-hydroxylation. These results suggest that human CYP2A6 and rat CYP2C11 are
the major catalysts in the metabolism of (â)-verbenone by liver microsomes and
that there are species-related differences in human and rat CYP2A enzymes and
sex-related differences in male and female rats in the metabolism of
(â)-verbenone. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0090-9556 1521-009X |
DOI: | 10.1124/dmd.31.8.1049 |