Benzo[a]pyrene diol epoxides: mechanism of enzymatic formation and optically active intermediates

Abstract

Studies of the mechanism of benzo[a]pyrene metabolism to reactive diol epoxides and of their disposition indicate that the metabolic intermediates of the activation pathways, 7,8-epoxide and trans-7,8-diol, as well as the two stereoisomeric diol epoxides are all optically active. Benzo[a]pyrene is converted to optically active 9,10-epoxides of (-)trans-7,8-diol by three enzymatic steps: (i) stereospecific oxygenation at the 7,8 double bond of benzo[a]pyrene by the mixed-function oxidases to essentially a single enantiomer of 7,8-epoxide, (ii) hydration of the 7,8-epoxide by epoxide hydratase to an optically pure (-)trans-7,8-diol, and (iii) stereoselective oxygenation by the mixed-function oxidases at the 9,10 double bond of the (-) trans-7,8-diol to optically active r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene and optically active r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a ratio of approximately 10 to 1.