Inter- and intramolecular deuterium isotope effects on the cytochrome P-450-catalyzed oxidative dehalogenation of 1,1,2,2-tetrachloroethane.
The oxidation of 1,1,2,2-tetrachloroethane to dichloroacetic acid was investigated with rat liver microsomes and purified cytochrome P-450. Deuterium substitution had no effect on Km values, but both the inter- and intramolecular isotope effects (kH/kD) on Vmax were in the range 5.7-6.1. The equivalence of the inter- and intramolecular values indicates that 6.0 may be a good estimate of the intrinsic isotope effect. The intermolecular kH/kD value for the conversion of 1,1,2,2-trichloroethane and its 1-2H analog to chloroacetic acid was 5.5. These data, and the finding that 1 atom of 18O was incorporated into the product when TCEA was oxidized in an 18O2 atmosphere, support an oxidative dechlorination mechanism that involves hydrogen atom abstraction by the P-450 intermediate oxo complex.
Hales
D B
DB
Molecular and Environmental Toxicology Program, School of Pharmacy, University of Colorado, Boulder 80309-0297.
Ho
B
B
Thompson
J A
JA
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D003903:Deuterium / Q000378:metabolism*; D004980:Ethane / Q000031:analogs & derivatives* / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D006843:Hydrocarbons, Chlorinated; C015530:1,1,2,2-tetrachloroethane; D003577:Cytochrome P-450 Enzyme System; D003903:Deuterium; D004980:Ethane