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The mechanism of metabolism of carbon tetrachloride (CCl4) to phosgene (COCl2) in rat liver microsomes was investigated. When the oxygen dependency of the reaction was studied, it was found that the rate of the reaction increased as the oxygen concentration in the reaction atmosphere was decreased from 100% to 5%. Decreasing the oxygen concentration below 5% caused a decrease in the rate of the reaction. The reaction was not inhibited by superoxide dismutase or catalase nor was it supported by cumene hydroperoxide. A reconstituted form of cytochrome P-450 from phenobarbital-pretreated rats metabolized CCl4 to COCl2. These results are consistent with a mechanism we call reductive oxygenation. The first step of the reaction is the cytochrome P-450-dependent reductive dechlorination of CCl4 to trichloromethyl radical (CCl3.). This intermediate is trapped by oxygen to form trichloromethylperoxyl radical (CCl3OO.), which decomposes to COCl2 and possibly an electrophilic form of chlorine.
L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
May 1988,
Biochemical pharmacology,
L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
June 1988,
Biochemical pharmacology,
L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
June 1980,
Life sciences,
L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
October 1980,
Biochemical pharmacology,
L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
January 1989,
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L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
January 1975,
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L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
January 1991,
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L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
July 1982,
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L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
January 1990,
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L R Pohl, and
R D Schulick, and
R J Highet, and
J W George
August 1971,
Hoppe-Seyler's Zeitschrift fur physiologische Chemie,
