Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate

John T. Groves, Gary A. McClusky, Ronald E. White, Minor J. Coon

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Abstract

The oxidation of norbornane by a reconstituted liver cytochrome P-450 system affords exo- and endo-2-norborneol in a ratio of 3.4:1. The ratio of these products was found to be 0.76:1 when exo,exo,exo,exo-2,3,5,6-tetradueteronorbornane was oxidized. Analysis of the mass spectra of the products from the deuterated hydrocarbon showed that 25% of the exo-norborneol contained four deuterium atoms whereas 9% of the endo-norborneol contained three deuterium atoms. These results, which indicate a very large isotope effect ( kH kD = 11.5±1) and a significant amount of epimerization for the hydroxylation of norbornane by cytochrome P-450, suggest an initial hydrogen abstraction to give a carbon radical intermediate.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume81
Issue number1
DOIs
StatePublished - Mar 15 1978
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology

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