Document Detail


Stereoselectivity of styrene oxidation in microsomes and in purified cytochrome P-450 enzymes from rat liver.
MedLine Citation:
PMID:  2918465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The stereochemistry of the cytochrome P-450(P-450)-dependent oxidation of styrene to styrene 7,8-oxide (SO) enantiomers was evaluated with rat hepatic microsomes and with individual rat liver P-450 enzymes in reconstituted monooxygenase systems. The stereoselectivity of the monooxygenase reaction with styrene was determined by high-performance liquid chromatographic analysis of the glutathione conjugates formed quantitatively from SO, the product of the monooxygenase reaction. Hepatic microsomes from control rats oxidized styrene at a rate of 13.1 +/- 4.5 nmol/min/nmol of P-450 and with a ratio of the amount of the (R)-styrene 7,8-oxide enantiomer to the amount of the (S)-styrene 7,8-oxide enantiomer (R/S) SO ratio of 0.65 +/- 0.1. These values were determined under incubation conditions in which epoxide hydrolase activity was inhibited by cyclohexene oxide, and at least 95% of the SO formed was converted enzymatically to glutathione conjugates. Treatment of rats i.p. with phenobarbital (PB) or beta-naphthoflavone (beta NF) caused changes in both parameters. Whereas the rates of oxidation in hepatic microsomes prepared from PB-treated rats was unchanged at 15.4 +/- 7.5 nmol/min/nmol of P-450 and decreased in hepatic microsomes from beta NF-treated rats to 9.4 +/- 2.8 nmol/min/nmol of P-450, the preference for formation of the R-enantiomer increased as the R/S ratio changed to 0.92 +/- 0.1 for PB and 1.25 +/- 0.1 for beta NF.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
G L Foureman; C Harris; F P Guengerich; J R Bend
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  248     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1989 Feb 
Date Detail:
Created Date:  1989-04-03     Completed Date:  1989-04-03     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  492-7     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzoflavones / pharmacology
Cytochrome P-450 Enzyme System / physiology*
Glutathione / metabolism
Liver / enzymology*
Male
Microsomes, Liver / metabolism*
Oxidation-Reduction
Phenobarbital / pharmacology
Rats
Rats, Inbred Strains
Stereoisomerism
Styrene
Styrenes / metabolism*
beta-Naphthoflavone
Chemical
Reg. No./Substance:
0/Benzoflavones; 0/Styrenes; 100-42-5/Styrene; 50-06-6/Phenobarbital; 6051-87-2/beta-Naphthoflavone; 70-18-8/Glutathione; 9035-51-2/Cytochrome P-450 Enzyme System

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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