Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol.

Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Research Abstract Details 

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Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Abstract Text:

N Murayama,M Minoshima,M Shimizu,F P Guengerich,H Yamazaki,

Human liver microsomal cytochrome P450s (P450s or CYP) involved in the oxidative biotransformation of the anesthetic agent propofol were investigated. Of six cDNA-expressed human P450 enzymes tested, CYP2B6 and CYP1A2, followed by CYP3A4, had high catalytic activities at a 20 microM propofol concentration, corresponding to clinical plasma levels. K(m) and k(cat) values for propofol omega- and 4-hydroxyation were 27 microM and 21 nmol omega-hydroxypropofol formed/min/nmol CYP2B6 and 30 microM and 42 nmol 4-hydroxypropofol formed/min/nmol CYP2B6, respectively. CYP2B6 expressed in HepG2 cells also effectively catalyzed propofol omega- and 4-hydroxylation. In a panel of individual human liver microsomes, propofol omega- and 4-hydroxylation activities (at the substrate concentration of 20 microM) were highly correlated with CYP2B6 contents, and moderately with CYP3A4 contents. Anti-CYP2B6 antibody inhibited both omega- and 4-hydroxylation activities in human liver samples that contained relatively high levels of CYP2B6, whereas alpha-naphthoflavone and an anti-CYP1A2 antibody showed inhibitory effects on the 4-hydroxylation activity in a liver microsomal sample in which the CYP1A2 level was relatively high. These results suggest that CYP2B6 has an important role in propofol omega- and 4-hydroxylation in human livers and that the hepatic contents of CYP2B6, CYP3A4, and CYP1A2 determine which P450 enzymes play major roles in propofol oxidation in individual humans.

Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Publishing Authors By Initials

N Murayama,M Minoshima,M Shimizu,FP Guengerich,H Yamazaki,

For similar enzymes and coenzymes: cytochromes: cytochrome p-450 enzyme system: steroid hydroxylases research abstracts see: enzymes and coenzymes: cytochromes: cytochrome p-450 enzyme system: steroid hydroxylases research

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Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Xenobiotica; the fate of foreign compounds in biol

VOLUME: 37

Page Numbers: 717-24

Journal Abbreviation: Xenobiotica

ISSN: 0049-8254

DAY: 3

MONTH: Jul

YEAR: 2007

Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 1306665

Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Keywords Mesh Terms:

KEYWORDS: Steroid Hydroxylases

MESH TERMS: physiology

Chemical & Substance for Abstract: Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Information

Substance Name: Aryl Hydrocarbon Hydroxylases

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol.

AFFILIATION: Showa Pharmaceutical University, Gakuen, Machida, Tokyo, Japan.

Country: England

AGENCY: United States NCI

GRANT: R37 CA090426

ACRONYM: CA

MEDLINETA: Xenobiotica

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