Abstract
Apparent deuterium and tritium kinetic isotope effects were measured on the O-demethylation of methoxychlor in uninduced and β-naphthoflavone-induced rat liver microsomes. From the apparent values, the magnitudes of the intrinsic deuterium isotope effect values were calculated by Northrop's method as 15.2 for uninduced and 19.2 for naphthoflavone-induced rat liver microsomes. The large values for the intrinsic isotope effect suggest that the C-H bond cleavage reaction in the O-demethylation catalyzed by microsomal cytochromes P-450 has a linear transition state in which there is no bonding between the carbon and hydrogen atoms. A comparison of the intrinsic isotope effect values with the apparent isotope effect values showed the presence of several partially rate-limiting steps in the O-demethylation of methoxychlor catalyzed by cytochromes P-450.
