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

doi:10.1016/0006-291X(78)91643-1

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

Research output: Contribution to journal › Article › peer-review

522 Scopus citations

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 ( k_H k_D = 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 language	English (US)
Pages (from-to)	154-160
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	81
Issue number	1
DOIs	https://doi.org/10.1016/0006-291X(78)91643-1
State	Published - Mar 15 1978
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Biophysics
Biochemistry
Cell Biology

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10.1016/0006-291X(78)91643-1

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@article{6823ab1c5062483f9543eddbb1463bb9,

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

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.",

author = "Groves, \{John T.\} and McClusky, \{Gary A.\} and White, \{Ronald E.\} and Coon, \{Minor J.\}",

note = "Funding Information: Acknowledgments. Financial support by the donors of the Petroleum Research Fund, administered by the American Chemical Society (JTG), The University of Michigan, National Science Foundation Grant PCM 76-14947 (MJC) and United States Public Health Services Grant AM-10339 (MJC) are gratefully acknowledged.",

year = "1978",

month = mar,

day = "15",

doi = "10.1016/0006-291X(78)91643-1",

language = "English (US)",

volume = "81",

pages = "154--160",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "1",

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TY - JOUR

T1 - Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate

AU - Groves, John T.

AU - McClusky, Gary A.

AU - White, Ronald E.

AU - Coon, Minor J.

N1 - Funding Information: Acknowledgments. Financial support by the donors of the Petroleum Research Fund, administered by the American Chemical Society (JTG), The University of Michigan, National Science Foundation Grant PCM 76-14947 (MJC) and United States Public Health Services Grant AM-10339 (MJC) are gratefully acknowledged.

PY - 1978/3/15

Y1 - 1978/3/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0017800253

UR - https://www.scopus.com/pages/publications/0017800253#tab=citedBy

U2 - 10.1016/0006-291X(78)91643-1

DO - 10.1016/0006-291X(78)91643-1

M3 - Article

C2 - 656092

AN - SCOPUS:0017800253

SN - 0006-291X

VL - 81

SP - 154

EP - 160

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

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

Abstract

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