286967-46-2Relevant articles and documents
Stereochemical Dynamics of Aliphatic Hydroxylation by Cytochrome P-450
White, Ronald E.,Miller, John P.,Favreau, Leonard V.,Bhattacharyya, Apares
, p. 6024 - 6031 (2007/10/02)
Previous studies on the stereochemistry of hydroxylation by cytochrome P-450 enzymes have been contradictory and confusing.Therefore, the hydroxylation of four isotopically substituted phenylethane substrates has been examined with a single isozyme of rabbit liver microsomal cytochrome P-450.In each case the corresponding 1-phenylethanol was essentially the only product.With ordinary phenylethane, the product was 48percent R-1-phenylethanol and 52percent the S isomer.With (R)-phenylethane-1-d, the product was 42percent R alcohol, while with (S)-phenylethane-1-d the product was 70percent R alcohol.When the substrate was phenylethane-1,1-d2, 50percent R alcohol was produced.The alcohols from the single-deuterium-substituted substrates were highly enriched in deuterium, indicating the operation of a large deuterium isotope effect on hydrogen removal.Most importantly, 23-40percent of the hydroxylation events resulted in alcohol with configuration opposite to that of the original hydrocarbon substrate.These "crossover" events require the intermediacy of a discrete tricoordinate carbon intermediate.These data unambiguously demonstrate that hydroxylation stereospecificity must be enforced by the surrounding protein tertiary structure and is not an inherent feature of the cytochrome P-450 reaction mechanism.
