1-Hydroxy- and 2-hydroxy-3-methylcholanthrene: regioselective and stereoselective formations in the metabolism of 3-methylcholanthrene and enantioselective disposition in rat liver microsomes.

Absolute configurations of enantiomeric 1-hydroxy-3-methylcholanthrene (1-OH-3MC) and 2-hydroxy-3-methyl-cholanthrene (2-OH-3MC) were determined by the exciton chirality circular dichroism (CD) method as their p-nitrobenzoate derivatives. Enantiomers of 1-OH-3MC were resolved by HPLC using a column packed with chiral stationary phase (CSP) (R)-N-(3,5-dinitrobenzoyl)phenylglycine covalently bonded to gamma-aminopropylsilanized silica. Enantiomers of 2-OH-3MC were resolved as diastereomeric (-)-methoxyacetates by normal-phase HPLC.

2-ketoacid dehydrogenase complexes of Escherichia coli: stereospecificities of the three components for (R)-lipoate.

Stereospecificities of component enzymes in the pyruvate dehydrogenase complex and 2-ketoglutarate dehydrogenase complex from Escherichia coli for lipoate and dihydrolipoate are determined. Assays of the component enzymes using R,S-, R-, or S-lipoate or the enantiomers of dihydrolipoate show that only the R-enantiomers are substrates for these enzymes. Nonenzymatic reactions involving acetyl group transfer and coupled electron and acetyl group transfer between enantiomeric molecules of lipoate or/and dihydrolipoate proceed at significant rates.

Stereoselectivity of cytochrome P-450 isozymes and epoxide hydrolase in the metabolism of polycyclic aromatic hydrocarbons.

Enantiomeric compositions of epoxides formed in the metabolism of planar benz[a]anthracene (BA), benzo[a]pyrene (BaP), and chrysene (CR), and nonplanar benzo[c]phenanthrene (BcPh), 12-methylbenz[a]anthracene (12-MBA) and 7,12-dimethylbenz[a]anthracene (7,12-DMBA) by liver microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats are determined either by direct chiral stationary phase HPLC analysis or by the enantiomeric compositions of metabolically formed trans-dihydrodiols. Cytochrome P-450 isozymes contained in various liver microsomal preparations have varying degrees of stereoselectivity in catalyzing the epoxidation reactions at various formal double bonds of the polycyclic aromatic hydrocarbons studied. In general, cytochrome P-450c, the major cytochrome P-450 isozyme contained in liver microsomes from 3-methylcholanthrene-treated rats, has the highest degree of stereoselectivity.

Stereoselective metabolism of chrysene by rat liver microsomes. Direct separation of diol enantiomers by chiral stationary phase h.p.l.c.

The direct enantiomeric resolution of non-K region trans-1,2-dihydrodiol, 1,2,3,4-tetrahydro-trans-1,2-diol, trans-3,4-dihydrodiol and 1,2,3,4-tetrahydro-trans-3,4-diol, K region trans- and cis-5,6-dihydrodiols and their monomethyl ethers of chrysene was studied by chiral stationary phase high-performance liquid chromatography (CSP-h.p.l.

The effect of the bay-region 12-methyl group on the stereoselective metabolism at the K-region of 7,12-dimethylbenz[a]anthracene by rat liver microsomes.

The enantiomers of a trans-5,6-dihydrodiol formed in the metabolism of 7,12-dimethylbenz[a]anthracene by rat liver microsomes (microsomal fractions) were resolved by chiral stationary-phase high-performance liquid chromatography. The major 7,12-dimethylbenz[a]anthracene trans-5,6-dihydrodiol enantiomer and its hydrogenation product 5,6,8,9,10,11-hexahydro-trans-5,6-diol were found to have 5S,6S absolute configurations by the exciton chirality c.d.