Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase. 1990

J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
Department of Medicine (Nephrology Division), Vanderbilt University Medical School, Nashville, Tennessee 37232.

Chiral analysis of the rat liver microsomal arachidonic acid epoxygenase metabolites shows enantioselective formation of 8,9-, 11,12-, and 14,15-cis-epoxyeicosatrienoic acids in an approximately 2:1, 4:1, and 2:1 ratio of antipodes, respectively. Animal treatment with the cytochrome P-450 inducer phenobarbital increased the overall enantiofacial selectivity of the microsomal epoxygenase and caused a concomitant inversion in the absolute configurations of its metabolites. These effects of phenobarbital were time-dependent and temporally linked to increases in the concentration of microsomal cytochrome P-450 enzymes. Reconstitution of the epoxygenase reaction utilizing several purified cytochrome P-450 demonstrated that the asymmetry of epoxidation is under cytochrome P-450 enzyme control. These results established that the chirality of the hepatic arachidonic acid epoxygenase is under regulatory control and confirm cytochromes P-450 IIB1 and IIB2 as two of the endogenous epoxygenases induced in vivo by phenobarbital.

UI MeSH Term Description Entries
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D010105 Oxygenases Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules. Oxygenase
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D000090762 Cytochrome P-450 CYP2J2 A cytochrome P450 enzyme involved in oxidizing POLYUNSATURATED FATTY ACIDS (PUFA) to PUFA epoxides which function as potent lipid mediators. This enzyme, encoded by CYP2J2 gene, metabolizes ARACHIDONIC ACID to epoxyeicosatrienoic acids (EETs) which produce biological effects including VASODILATION. Arachidonate Epoxygenase,Arachidonic Acid Epoxygenase,Cytochrome P-450 Arachidonate Oxygenase,Cytochrome P-450 Epoxygenase,NADPH-Dependent Arachidonic Acid Epoxygenase,CYP2J2,Acid Epoxygenase, Arachidonic,Cytochrome P 450 Arachidonate Oxygenase,Cytochrome P 450 CYP2J2,Epoxygenase, Arachidonate,Epoxygenase, Arachidonic Acid,NADPH Dependent Arachidonic Acid Epoxygenase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001571 Benzoflavones Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered. Benzoflavone Compounds,Compounds, Benzoflavone
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer

Related Publications

J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
January 1989, Advances in prostaglandin, thromboxane, and leukotriene research,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
May 2006, American journal of physiology. Renal physiology,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
February 1988, The Journal of biological chemistry,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
April 1988, The American journal of the medical sciences,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
September 1981, Proceedings of the National Academy of Sciences of the United States of America,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
December 1988, Pharmacological reviews,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
September 1999, The Journal of clinical investigation,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
November 2002, Analytical chemistry,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
November 2002, Analytical chemistry,
J H Capdevila, and A Karara, and D J Waxman, and M V Martin, and J R Falck, and F P Guenguerich
January 1991, Annual review of pharmacology and toxicology,
Copied contents to your clipboard!