Stereoselectivity of cytochrome P-450c in the formation of naphthalene and anthracene 1,2-oxides
Absolute configurations of the arene 1,2-oxides formed from naphthalene and anthracene by cytochrome P-450c, the predominant isozyme of cytochrome P-450 found in the livers of rats treated with 3-methylcholanthrene, were determined via two different approaches. The first consisted of trapping the arene oxides with N-acetyl-L-cysteine to form S-conjugates, methylation of the conjugates with diazomethane, and separation of the resulting diastereomeric esters by reversed phase high performance liquid chromatography. Analysis by this procedure of the arene oxides formed from radioactive naphthalene and anthracene by a highly purified and reconstituted monooxygenase system containing cytochrome P-450c in dicated that 73 and greater than or equal to95%, respectively, of the metabolically formed arene oxides consisted of the (+)-(1R,2S)-enantiomer. In the second approach, each hydrocarbon was incubated with a reconstituted system containing both cytochrome P-450c and epoxide hydrolase. Under these conditions, the predominant metabolites are trans-1,2-dihydrodiols formed by epoxide hydrolase catalyzed trans-addition of water to the arene oxide intermediates. In both cases, the (-)-(1R,2R)-dihydrodiols predominated; 92% for naphthalene and 99% for anthracene. Qualitatively and quantitatively both approaches indicate that the (+)-arene (1R,2S)-oxides predominate. The results are discussed in terms of the steric constraints of a proposed model for the catalytic binding site of cytochrome P-450c.
- Research Organization:
- National Institutes of Health, Bethesda, MD
- OSTI ID:
- 5694650
- Journal Information:
- J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 259:14; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTHRACENE
AROMATICS
BODY
CARBON 14 COMPOUNDS
CONDENSED AROMATICS
CYTOCHROMES
DATA
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
EXPERIMENTAL DATA
GLANDS
HYDROCARBONS
HYDROLASES
INFORMATION
ISOENZYMES
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
METABOLITES
NAPHTHALENE
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PIGMENTS
POLYCYCLIC AROMATIC HYDROCARBONS
RATS
RODENTS
STEREOCHEMISTRY
VERTEBRATES